CA2559302A1 - 6-amino-1h-pyrimidine-2,4-dione derivatives as dipeptidyl peptidase inhibitors - Google Patents

6-amino-1h-pyrimidine-2,4-dione derivatives as dipeptidyl peptidase inhibitors Download PDF

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CA2559302A1
CA2559302A1 CA002559302A CA2559302A CA2559302A1 CA 2559302 A1 CA2559302 A1 CA 2559302A1 CA 002559302 A CA002559302 A CA 002559302A CA 2559302 A CA2559302 A CA 2559302A CA 2559302 A1 CA2559302 A1 CA 2559302A1
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alkyl
group
phenyl
amino
cycloalkyl
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CA2559302C (en
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Jun Feng
Stephen L. Gwaltney
Jeffrey A. Stafford
Zhiyuan Zhang
Bruce Elder
Paul Isbester
Grant Palmer
Jonathon Salsbury
Luckner Ulysse
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Takeda Pharmaceutical Co Ltd
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Abstract

Compounds, pharmaceuticals, kits and methods are provided for use with DPP-IV
and other S9 proteases that comprise a compound comprising Formula (I):
STR1 wherein M is N or CR4; Q1 and Q2 are each independently selected from the group consisting of CO, SO, SO2, and C=NR9; and each R1, R2, R3, R4 and R9 are as defined herein.

Claims (37)

1. A compound comprising:
wherein Mo is -C-LX, N or CR4;
Q1 and Q2 are each independently selected from the group consisting of CO, CS, SO, SO2, and C=NR9;
R0 is R1 or -LX, with the proviso that only one of R0 and M0 is -LX;
R1 is hydrogen or is selected from the group consisting of halo, perhalo(C1-10)alkyl, amino, cyano, thio, (C1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;
R2 is hydrogen or selected from the group consisting of (C1-10)alkyl, (C3-12)cycloalkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-12)bicycloaryl, hetero(C4-12)bicycloaryl(C1-5)alkyl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;
R3 is selected from the group consisting of perhalo(C1-10)alkyl, amino, (C1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted, and a substituted or unsubstituted 3, 4, 5, 6 or 7 membered ring;
R4 is hydrogen or is selected from the group consisting of halo, perhalo(C1-10)alkyl, amino, cyano, thio, (C1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;
R9 is hydrogen or is selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, bicycloaryl, and heterobicycloaryl, each substituted or unsubstituted;
L is a linker providing 1, 2 or 3 atom separation between X and the ring to which L is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur; and X is selected from the group consisting of (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-12)bicycloaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, alkenyl, alkynyl, carbonyl group, cyano, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.
2. A compound according to claim 1 comprising:
wherein M is N or CR4;
Q1 and Q2 are each independently selected from the group consisting of CO, CS, SO, SO2, and C=NR9;

R2 is hydrogen or selected from the group consisting of (C1-10)alkyl, (C3-12)cycloalkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-12)bicycloaryl, hetero(C4-12)bicycloaryl(C1-5)alkyl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-
3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;

R3 is selected from the group consisting of perhalo(C1-10)alkyl, amino, (C1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted, and a substituted or unsubstituted 3, 4, 5, 6 or 7 membered ring;

R4 is hydrogen or is selected from the group consisting of halo, perhalo(C1-10)alkyl, amino, cyano, thio, (C1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;

R9 is hydrogen or is selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, bicycloaryl, and heterobicycloaryl, each substituted or unsubstituted;

L is a linker providing 1, 2 or 3 atom separation between X and the ring to which L is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur; and X is selected from the group consisting of (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-12)bicycloaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, alkenyl, alkynyl, carbonyl group, cyano, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

3. ~~A compound according to claim 2 comprising:
wherein M is N or CR4;
R2 is hydrogen or selected from the group consisting of (C1-10)alkyl, (C3-12)cycloalkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-12)bicycloaryl, hetero(C4-12)bicycloaryl(C1-5)alkyl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;
R3 is selected from the group consisting of perhalo(C1-10)alkyl, amino, (C1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted, and a substituted or unsubstituted 3, 4, 5, 6 or 7 membered ring;
R4 is hydrogen or is selected from the group consisting of halo, perhalo(C1-10)alkyl, amino, cyano, thio, (C1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;
L is a linker providing 1, 2 or 3 atom separation between X and the ring to which L is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur; and X is selected from the group consisting of (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-12)bicycloaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, alkenyl, alkynyl, carbonyl group, cyano, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.
4. ~The compound according to any one of claims 1-3, wherein the 1, 2 or 3 atoms of L
providing the separation consist of carbon atoms.
5. ~The compound according to any one of claims 1-3, wherein the 1, 2 or 3 atoms of L
providing the separation are selected from the group of linkers consisting of at least one oxygen or at least one nitrogen atom.
6. ~The compound according to any one of claims 1-3, wherein L separates X
from the ring atom by one atom.
7. ~The compound according to any one of claims 1-3, wherein L is selected from the group consisting of -CH2-, -CH2CH2-, -CH2CH2CH2-, -C(O)-, -CH2C(O)-, -C(O)CH2-, -CH2-C(O)CH2-, -C(O)CH2CH2-, -CH2CH2C(O)-, -O-, -OCH2-, -CH2O-, -CH2OCH2-, -OCH2CH2-, -CH2CH2O, -N(CH3)-, -NHCH2-, -CH2NH-, -CH2NHCH2-, -NHCH2CH2-, -CH2CH2NH-, -NH-C(O)-, -NCH3-C(O)-, -C(O)NH-, -C(O)NCH3-, -NHC(O)CH2-, -C(O)NHCH2-, -C(O)CH2NH-, -CH2NHC(O)-, -CH2C(O)NH-, -NHCH2C(O)-, -S-, -SCH2-, -CH2S-, -SCH2CH2-, -CH2SCH2-, -CH2CH2S-, -C(O)S-, -C(O)SCH2-, -CH2C(O)S-, -C(O)CH2S-, and -CH2SC(O)-, each substituted or unsubstituted.
8. ~The compound according to any one of claims 1-3, wherein L is selected from the group consisting of -CH2-, -C(O)-, -CH2C(O)-, -C(O)CH2-, -CH2-C(O)CH2-, -C(O)CH2CH2-, and -CH2CH2C(O)-, each substituted or unsubstituted.
9. The compound according to any one of claims 1-3, wherein -L-X taken together is selected from the group consisting of -(CH2)-(2-cyano)phenyl; -(CH2)-(3-cyano)phenyl; -(CH2)-(2-hydroxy)phenyl; -(CH2)-(3-hydroxy)phenyl; -(CH2)-(2-alkenyl)phenyl; -(CH2)-(3-alkenyl)phenyl; -(CH2)-(2-alkynyl)phenyl; -(CH2)-(3-alkynyl)phenyl; -(CH2)-(2-methoxy)phenyl; -(CH2)-(3-methoxy)phenyl; -(CH2)-(2-nitro)phenyl; -(CH2)-(3-nitro)phenyl;
-(CH2)-(2-carboxy)phenyl; -(CH2)-(3-carboxy)phenyl; -(CH2)-(2-carboxamido)phenyl; -(CH2)-(3-carboxamido)phenyl; -(CH2)-(2-sulfonamido)phenyl; -(CH2)-(3-sulfonamido)phenyl; -(CH2)-(2-tetrazolyl)phenyl; -(CH2)-(3-tetrazolyl)phenyl; -(CH2)-(2-aminomethyl)phenyl; -(CH2)-(3-aminomethyl)phenyl; -(CH2)-(2-hydroxymethyl)phenyl; -(CH2)-(3-hydroxymethyl)phenyl; -(CH2)-(2-phenyl)phenyl; -(CH2)-(3-phenyl)phenyl; -(CH2)-(2-halo)phenyl; -(CH2)-(3-halo)phenyl; -(CH2)-(2-CONH2)phenyl; -(CH2)-(3-CONH2)phenyl;
-(CH2)-(2-CONH(C1-7)alkyl)phenyl; -(CH2)-(3-CONH(C1-7)alkyl)phenyl; -(CH2)-(2-CO2(C1-7)alkyl)phenyl; -(CH2)-(3-CO2(C1-7)alkyl)phenyl; -(CH2)-(2-NH2)phenyl; -(CH2)-(3-NH2)phenyl; -(CH2)-(2-(C3-7)alkyl)phenyl; -(CH2)-(3-(C3-7)alkyl)phenyl; -(CH2)-(2-(C3-7)cycloalkyl)phenyl; -(CH2)-(3-(C3-7)cycloalkyl)phenyl; -(CH2)-(2-aryl)phenyl; -(CH2)-(3-aryl)phenyl; -(CH2)-(2-heteroaryl)phenyl; -(CH2)-(3-heteroaryl)phenyl; -(CH2)-2-bromo-5-fluoro phenyl; -(CH2)-2-chloro-5-fluoro phenyl; -(CH2)-2-cyano-5-fluoro phenyl; -(CH2)-2,5-dichloro phenyl; -(CH2)-2,5-difluoro phenyl; -(CH2)-2,5-dibromo phenyl; -(CH2)-2-bromo-3,5-difluoro phenyl; -(CH2)-2-chloro-3,5-difluoro phenyl; -(CH2)-2,3,5-trifluoro phenyl; -(CH2)-2,3,5,6-tetrafluorophenyl; -(CH2)-2-bromo-3,5,6-trifluoro phenyl; -(CH2)-2-chloro-3,5,6-trifluoro phenyl; -(CH2)-2-cyano-3,5-difluoro phenyl; -(CH2)-2-cyano-3,5,6-trifluoro phenyl; -(CH2)-(2-heterocycloalkyl)phenyl; and -(CH2)-(3-heterocycloalkyl)phenyl, each substituted or unsubstituted.
10. A compound according to claim 2 comprising:
wherein n is 1, 2, or 3;
M is N or CR4;
Q1 and Q2 are each independently selected from the group consisting of CO, CS, SO, SO2, and C=NR9;
R2 is hydrogen or selected from the group consisting of (C1-10)alkyl, (C3-12)cycloalkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-12)bicycloaryl, hetero(C4-12)bicycloaryl(C1-5)alkyl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;
R3 is selected from the group consisting of perhalo(C1-10)alkyl, amino, (C1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted, and a substituted or unsubstituted 3, 4, 5, 6 or 7 membered ring;
R4 is hydrogen or is selected from the group consisting of halo, perhalo(C1-10)alkyl, amino, cyano, thio, (C1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;
each R5 and R6 is independently hydrogen or is selected from the group consisting of a substituted or unsubstituted (C1-10)alkyl, a substituted or unsubstituted (C1-10)alkoxy, cyano, and halo, or where R5 and R6 are taken together to form a ring;
R9 is hydrogen or is selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, bicycloaryl, and heterobicycloaryl, each substituted or unsubstituted; and X is selected from the group consisting of (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C3-12)bicycloaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, alkenyl, alkynyl, carbonyl group, cyano, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.
11. ~The compound according to any one of claims 1-10, wherein X is a substituted or unsubstituted (C3-7)cycloalkyl, (C3-7)heterocycloalkyl, aryl, phenyl, heteroaryl, halophenyl, dihalophenyl, haloaryl, haloheteroaryl, dihaloaryl, dihaloheteroaryl, or a ring-bearing or cyclic group having a non-hydrogen substituent at a 2 or 3 position of the ring, each substituted or unsubstituted.
12. ~The compound according to any one of claims 1-10, wherein X is a ring-bearing or cyclic group having a non-hydrogen substituent at a 2 or 3 position of the ring selected from the group consisting of (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-12)bicycloaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, cyano, nitro, halo, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.
13.
14. ~The compound according to any one of claims 1-10, wherein X is selected from the group consisting of (2-cyano)phenyl; (3-cyano)phenyl; (2-hydroxy)phenyl; (3-hydroxy)phenyl;
(2-alkenyl)phenyl; (3-alkenyl)phenyl; (2-alkynyl)phenyl; (3-alkynyl)phenyl; (2-methoxy)phenyl; (3-methoxy)phenyl; (2-nitro)phenyl; (3-nitro)phenyl; (2-carboxy)phenyl; (3-carboxy)phenyl; -(CH2)-(2-carboxamido)phenyl; (3-carboxamido)phenyl; (2-sulfonamido)phenyl; (3-sulfonamido)phenyl; (2-tetrazolyl)phenyl; (3-tetrazolyl)phenyl;
(2-aminomethyl)phenyl; (3-aminomethyl)phenyl; (2-hydroxymethyl)phenyl;
(3-hydroxymethyl)phenyl; (2-phenyl)phenyl; (3-phenyl)phenyl; (2-halo)phenyl;
(3-halo)phenyl; (2-CONH2)phenyl; (3-CONH2)phenyl; (2-CONH(C1-7)alkyl)phenyl;
(3-CONH(C1-7)alkyl)phenyl; (2-CO2(C1-7)alkyl)phenyl; (3-CO2(C1-7)alkyl)phenyl;
(2-NH2)phenyl; (3-NH2)phenyl; (2-(C3-7)alkyl)phenyl; (3-(C3-7)alkyl)phenyl;
(2-(C3-7)cycloalkyl)phenyl; (3-(C3-7)cycloalkyl)phenyl; (2-aryl)phenyl; (3-aryl)phenyl;
(2-heteroaryl)phenyl; (3-heteroaryl)phenyl; 2-bromo-5-fluoro phenyl; 2-chloro-5-fluoro phenyl; 2-cyano-5-fluoro phenyl; 2,5-dichloro phenyl; 2,5-difluoro phenyl; 2,5-dibromo phenyl; 2-bromo-3,5-difluoro phenyl; 2-chloro-3,5-difluoro phenyl; 2,3,5-trifluoro phenyl;
2,3,5,6-tetrafluorophenyl; 2-bromo-3,5,6-trifluoro phenyl; 2-chloro-3,5,6-trifluoro phenyl; 2-cyano-3,5-difluoro phenyl; 2-cyano-3,5,6-trifluoro phenyl; (2-heterocycloalkyl)phenyl; and (3-heterocycloalkyl)phenyl, each substituted or unsubstituted.
15. ~The compound according to any one of claims 1-10, wherein X is selected from the group consisting of wherein A is S, O or NR24;
B is CR23 or N;
R23 is independently selected from the group consisting of hydrogen, halo, perhalo(C1-10)alkyl, amino, thio, cyano, CF3, nitro, (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl (C1-5)alkyl, (C9-12)bicycloaryl, hetero(C8-12)bicycloaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, imino group, carbonyl group, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, and sulfinyl group, each substituted or unsubstituted; and R24 is independently selected from the group consisting of hydrogen, perhalo(C1-10)alkyl, amino, (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl (C1-5)alkyl, (C9-12)bicycloaryl, hetero(C8-12)bicycloaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, imino group, carbonyl group, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, and sulfinyl group, each substituted or unsubstituted.
16. ~The compound according to any one of claims 1-10, wherein X is selected from the group consisting of wherein t is 0, 1, 2, 3, 4 or 5; and each R7 is independently selected from the group consisting of halo, perhalo(C1-10)alkyl, CF3, (C1-10)alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, cyano, nitro, hydroxy, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.
17. ~The compound according to any one of claims 1-10, wherein X is selected from the group consisting of wherein s is 0, 1, 2, or 3; and each R7 is independently selected from the group consisting of halo, perhalo(C1-10)alkyl, CF3, (C1-10)alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, cyano, nitro, hydroxy, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.
18. ~The compound according to claim 16 or 17 wherein R7 is independently selected from the group consisting of -cyano, -methoxy, -nitro, -carboxy, -sulfonamido, -tetrazolyl, -aminomethyl, -hydroxymethyl, -phenyl, -halo, -CONH2, -CONH(C1-7)alkyl, -CO2(C1-7)alkyl, -NH2, -OH, -(C1-5)alkyl, -alkenyl, -alkynyl, (C1-5)cycloalkyl, aryl, heteroaryl, and heterocycloalkyl, each substituted or unsubstituted.
19. ~A compound according to claim 10 comprising:
wherein m is 0,1,2,3,4, or 5;
n is 1,2, or 3;
M is N or CR4;
Q1 and Q2 are each independently selected from the group consisting of CO, CS, SO, SO2, and C=NR9;
R2 is hydrogen or selected from the group consisting of (C1-10)alkyl, (C3-12)cycloalkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-12)bicycloaryl, hetero(C4-12)bicycloaryl(C1-5)alkyl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;
R3 is selected from the group consisting of perhalo(C1-10)alkyl, amino, (C1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted, and a substituted or unsubstituted 3, 4, 5, 6 or 7 membered ring;

R4 is hydrogen or is selected from the group consisting of halo, perhalo(C1-10)alkyl, amino, cyano, thio, (C1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;
each R5 and R6 is independently hydrogen or is selected from the group consisting of a substituted or unsubstituted (C1-10)alkyl, a substituted or unsubstituted (C1-10)alkoxy, cyano, and halo, or where R5 and R6 are taken together to form a ring;
each R7 is independently selected from the group consisting of halo, perhalo(C1-10)alkyl, CF3, (C1-10)alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, cyano, nitro, hydroxy, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted; and R9 is hydrogen or is selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, bicycloaryl, and heterobicycloaryl, each substituted or unsubstituted.
20. ~A compound according to claim 10 comprising:
a member selected from the group consisting of wherein n is 1, 2, or 3;
M is N or CR4;
each of T, U, V, W and Y is independently nitrogen or CR16, provided that no more than two of T, U, V, W and Y are nitrogen;

Q1 and Q2 are each independently selected from the group consisting of CO, CS, SO, SO2, and C=NR9;

R2 is hydrogen or selected from the group consisting of (C1-C10)alkyl, (C3-12)cycloalkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl, aryl(C1-C10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-12)bicycloaryl, hetero(C4-12)bicycloaryl(C1-5)alkyl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;

R3 is selected from the group consisting of perhalo(C1-10)alkyl, amino, (C1-C10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted, and a substituted or unsubstituted 3, 4, 5, 6 or 7 membered ring;

R4 is hydrogen or is selected from the group consisting of halo, perhalo(C1-C10)alkyl, amino, cyano, thio, (C1-C10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;

each R5 and R6 is independently hydrogen or is selected from the group consisting of a substituted or unsubstituted (C1-10)alkyl, a substituted or unsubstituted (C1-C10)alkoxy, cyano, and halo, or where R5 and R6 are taken together to form a ring;

R9 is hydrogen or is selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, bicycloaryl, and heterobicycloaryl, each substituted or unsubstituted; and each R16 is independently selected from the group consisting of halo, perhalo(C1-10)alkyl, CF3, (C1-10)alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thin, cyano, nitro, hydroxy, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.
21. A compound according to claim 1 comprising:

wherein Q1 and Q2 are each independently selected from the group consisting of CO, CS, SO, SO2, and C=NR9;

R1 is hydrogen or is selected from the group consisting of halo, perhalo(C1-10)alkyl, amino, cyano, thio, (C1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;

R2 is hydrogen or selected from the group consisting of (C1-10)alkyl, (C3-12)cycloalkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-12)bicycloaryl, hetero(C4-12)bicycloaryl(C1-5)alkyl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;

R3 is selected from the group consisting of perhalo(C1-10)alkyl, amino, (C1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted, and a substituted or unsubstituted 3, 4, 5, 6 or 7 membered ring;

R9 is hydrogen or is selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, bicycloaryl, and heterobicycloaryl, each substituted or unsubstituted;

L is a linker providing 1, 2 or 3 atom separation between X and the ring to which L is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur; and X is selected from the group consisting of (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-12)bicycloaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, alkenyl, alkynyl, carbonyl group, cyano, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.
22. A compound according to claim 21 comprising:

wherein R1 is hydrogen or is selected from the group consisting of halo, perhalo(C1-10)alkyl, amino, cyano, thio, (C1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;

R2 is hydrogen or selected from the group consisting of (C1-10)alkyl, (C3-12)cycloalkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-12)bicycloaryl, hetero(C4-12)bicycloaryl(C1-5)alkyl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;

R3 is selected from the group consisting of perhalo(C1-10)alkyl, amino, (C1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted, and a substituted or unsubstituted 3, 4, 5, 6 or 7 membered ring;

L is a linker providing 1, 2 or 3 atom separation between X and the ring to which L is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur; and X is selected from the group consisting of (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-12)bicycloaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, alkenyl, alkynyl, carbonyl group, cyano, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.
23. The compound according to claim 21 or 22, wherein the 1, 2 or 3 atoms of L
providing the separation consist of carbon atoms.
24. The compound according to claim 21 or 22, wherein the 1, 2 or 3 atoms of L
providing the separation are selected from the group of linkers consisting of at least one oxygen or at least one nitrogen atom.
25. The compound according to claim 21 or 22, wherein L separates X from the ring atom by one atom.
26. The compound according to claim 21 or 22, wherein L is selected from the group consisting of -CH2-, -CH2CH2-, -CH2CH2CH2-, -C(O)-, -CH2C(O)-, -C(O)CH2-, -CH2-C(O)CH2-, -C(O)CH2CH2-, -CH2CH2C(O)-, -O-, -OCH2-, -CH2O-, -CH2OCH2-, -OCH2CH2-, -CH2CH2O-, -N(CH3)-, -NHCH2-, -CH2NH-, -CH2NHCH2-, -NHCH2CH2-, -CH2CH2NH-, -NH-C(O)-, -NCH3-C(O)-, -C(O)NH-, -C(O)NCH3-, -NHC(O)CH2,-, -C(O)NHCH2-, -C(O)CH2NH-, -CH2NHC(O)-, -CH2C(O)NH-, -NHCH2C(O)-, -S-, -SCH2-, -CH2S-, -SCH2CH2-, -CH2SCH2-, -CH2CH2S-, -C(O)S-, -C(O)SCH2-, -CH2C(O)S-, -C(O)CH2S-, and -CH2SC(O)-, each substituted or unsubstituted.
27. The compound according to claim 21 or 22, wherein L is selected from the group consisting of -CH2-, -C(O)-, -CH2C(O)-, -C(O)CH2-, -CH2-C(O)CH2-, -C(O)CH2CH2-, and -CH2CH2C(O)-, each substituted or unsubstituted.
28. The compound according to claim 21 or 22, wherein -L-X taken together is selected from the group consisting of -(CH2)-(2-cyano)phenyl; -(CH2)-(3-cyano)phenyl; -(CH2)-(2-hydroxy)phenyl; -(CH2)-(3-hydroxy)phenyl; -(CH2)-(2-alkenyl)phenyl; -(CH2)-(3-alkenyl)phenyl; -(CH2)-(2-alkynyl)phenyl; -(CH2)-(3-alkynyl)phenyl; -(CH2)-(2-methoxy)phenyl; -(CH2)-(3-methoxy)phenyl; -(CH2)-(2-nitro)phenyl; -(CH2)-(3-nitro)phenyl;
-(CH2)-(2-carboxy)phenyl; -(CH2)-(3-carboxy)phenyl; -(CH2)-(2-carboxamido)phenyl; -(CH2)-(3-carboxamido)phenyl; -(CH2)-(2-sulfonamido)phenyl; -(CH2)-(3-sulfonamido)phenyl; -(CH2)-(2-tetrazolyl)phenyl; -(CH2)-(3-tetrazolyl)phenyl; -(CH2)-(2-aminomethyl)phenyl; -(CH2)-(3-aminomethyl)phenyl; -(CH2)-(2-hydroxymethyl)phenyl; -(CH2)-(3-hydroxymethyl)phenyl; -(CH2)-(2-phenyl)phenyl; -(CH2)-(3-phenyl)phenyl; -(CH2)-(2-halo)phenyl; -(CH2)-(3-halo)phenyl; -(CH2)-(2-CONH2)phenyl; -(CH2)-(3-CONH2)phenyl;
-(CH2)-(2-CONH(Cl-~)alkyl)phenyl; -(CH2)-(3-CONH(C1-7)alkyl)phenyl; -(CH2)-(2-CO2(C1-7)alkyl)phenyl; -(CH2)-(3-CO2(C1-7)alkyl)phenyl; -(CH2)-(2-NH2)phenyl; -(CH2)-(3-NH2)phenyl; -(CH2)-(2-(C3-7)alkyl)phenyl; -(CH2)-(3-(C3-7)alkyl)phenyl; -(CH2)-(2-(C3-7)cycloalkyl)phenyl; -(CH2)-(3-(C3-7)cycloalkyl)phenyl; -(CH2)-(2-aryl)phenyl; -(CH2)-(3-aryl)phenyl; -(CH2)-(2-heteroaryl)phenyl; -(CH2)-(3-heteroaryl)phenyl; -(CH2)-2-bromo-5-fluoro phenyl; -(CH2)-2-chloro-5-fluoro phenyl; -(CH2)-2-cyano-5-fluoro phenyl; -(CH2)-2,5-dichloro phenyl; -(CH2)-2,5-difluoro phenyl; -(CH2)-2,5-dibromo phenyl; -(CH2)-2-bromo-3,5-difluoro phenyl; -(CH2)-2-chloro-3,5-difluoro phenyl; -(CH2)-2,3,5-trifluoro phenyl; -(CH2)-2,3,5,6-tetrafluorophenyl; -(CH2)-2-bromo-3,5,6-trifluoro phenyl; -(CH2)-2-chloro-3,5,6-trifluoro phenyl; -(CH2)-2-cyano-3,5-difluoro phenyl; -(CH2)-2-cyano-3,5,6-trifluoro phenyl; -(CH2)-(2-heterocycloalkyl)phenyl; and -(CH2)-(3-heterocycloalkyl)phenyl, each substituted or unsubstituted.
29. A compound according to claim 21 comprising:
wherein n is 1, 2, or 3;
Q1 and Q2 are each independently selected from the group consisting of CO, CS, SO, SO2, and C=NR9;
R1 is hydrogen or is selected from the group consisting of halo, perhalo(C1-10)alkyl, amino, cyano, thio, (C1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;
R2 is hydrogen or selected from the group consisting of (C1-10)alkyl, (C3-12)cycloalkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-12)bicycloaryl, hetero(C4-12)bicycloaryl(C1-5)alkyl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;
R3 is selected from the group consisting of perhalo(C1-10)alkyl, amino, (C1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted, and a substituted or unsubstituted 3, 4, 5, 6 or 7 membered ring;

each R5 and R6 is independently hydrogen or is selected from the group consisting of a substituted or unsubstituted (C1-10)alkyl, a substituted or unsubstituted (C1-10)alkoxy, cyano, and halo, or where R5 and R6 are taken together to form a ring;
R9 is hydrogen or is selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, bicycloaryl, and heterobicycloaryl, each substituted or unsubstituted; and X is selected from the group consisting of (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-12)bicycloaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, alkenyl, alkynyl, carbonyl group, cyano, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.
30. The compound according to any one of claims 22-29, wherein X is a substituted or unsubstituted (C3-7)cycloalkyl.
31. The compound according to any one of claims 22-29, wherein X is a substituted or unsubstituted (C3-7)heterocycloalkyl.
32. The compound according to any one of claims 22-29, wherein X is a substituted or unsubstituted aryl.
33. The compound according to any one of claims 22-29, wherein X is a substituted or unsubstituted phenyl.
34. The compound according to any one of claims 22-29, wherein X is a substituted or unsubstituted heteroaryl.
35. The compound according to any one of claims 22-29, wherein X is a ring having a non-hydrogen substituent at a 2 or 3 position of the ring.
36. The compound according to any one of claims 22-29, wherein X is a ring having a non-hydrogen substituent at a 2 or 3 position of the ring selected from the group consisting of (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C1-12)bicycloaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, cyano, nitro, halo, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.
37. The compound according to any one of claims 22-29, wherein X is a substituted or unsubstituted halophenyl or dihalophenyl.
3g. The compound according to any one of claims 22-29, wherein X is a substituted or unsubstituted haloaryl, haloheteroaryl, dihaloaryl or dihaloheteroaryl.
39. The compound according to any one of claims 22-29, wherein X is selected from the group consisting of (2-cyano)phenyl; (3-cyano)phenyl; (2-hydroxy)phenyl; (3-hydroxy)phenyl;
(2-alkenyl)phenyl; (3-alkenyl)phenyl; (2-alkynyl)phenyl; (3-alkynyl)phenyl; (2-methoxy)phenyl; (3-methoxy)phenyl; (2-nitro)phenyl; (3-nitro)phenyl; (2-carboxy)phenyl; (3-carboxy)phenyl; -(CH2)-(2-carboxamido)phenyl; (3-carboxamido)phenyl; (2-sulfonamido)phenyl; (3-sulfonamido)phenyl; (2-tetrazolyl)phenyl; (3-tetrazolyl)phenyl;
(2-aminomethyl)phenyl; (3-aminomethyl)phenyl; (2-hydroxymethyl)phenyl;
(3-hydroxymethyl)phenyl; (2-phenyl)phenyl; (3-phenyl)phenyl; (2-halo)phenyl;
(3-halo)phenyl; (2-CONH2)phenyl; (3-CONH2)phenyl; (2-CONH(C1-7)alkyl)phenyl;
(3-CONH(C1-7)alkyl)phenyl; (2-CO2(C1-7)alkyl)phenyl; (3-CO2(C1-7)alkyl)phenyl;
(2-NH2)phenyl; (3-NH2)phenyl; (2-(C3-7)alkyl)phenyl; (3-(C3-7)alkyl)phenyl;
(2-(C3-7)cycloalkyl)phenyl; (3-(C3-7)cycloalkyl)phenyl; (2-aryl)phenyl; (3-aryl)phenyl;
(2-heteroaryl)phenyl; (3-heteroaryl)phenyl; 2-bromo-5-fluoro phenyl; 2-chloro-5-fluoro phenyl; 2-cyano-5-fluoro phenyl; 2,5-dichloro phenyl; 2,5-difluoro phenyl; 2,5-dibromo phenyl; 2-bromo-3,5-difluoro phenyl; 2-chloro-3,5-difluoro phenyl; 2,3,5-trifluoro phenyl;
2,3,5,6-tetrafluorophenyl; 2-bromo-3,5,6-trifluoro phenyl; 2-chloro-3,5,6-trifluoro phenyl; 2-cyano-3,5-difluoro phenyl; 2-cyano-3,5,6-trifluoro phenyl; (2-heterocycloalkyl)phenyl; and (3-heterocycloalkyl)phenyl, each substituted or unsubstituted.
40. The compound according to any one of claims 22-29, wherein X is selected from the group consisting of wherein A is S, O or NR24;
B is CR23 or N;
R23 is independently selected from the group consisting of hydrogen, halo, perhalo(C1-10)alkyl, amino, thio, cyano, CF3, nitro, (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl (C1-5)alkyl, (C9-12)bicycloaryl, hetero(C8-12)bicycloaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, imino group, carbonyl group, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, and sulfinyl group, each substituted or unsubstituted; and R24 is independently selected from the group consisting of hydrogen, perhalo(C1-10)alkyl, amino, (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl (C1-5)alkyl, (C9-12)bicycloaryl, hetero(C8-12)bicycloaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, imino group, carbonyl group, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, and sulfinyl group, each substituted or unsubstituted.
41. The compound according to any one of claims 22-29, wherein X is selected from the group consisting of wherein t is 0, 1, 2, 3, 4, or 5; and each R7 is independently selected from the group consisting of halo, perhalo(C1-10)alkyl, CF3, (C1-10)alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, cyano, nitro, hydroxy, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.
42. A compound according to any one of claims 22-29, wherein X is selected from the group consisting of wherein s is 0, 1, 2, or 3; and each R7 is independently selected from the group consisting of halo, perhalo(C1-10)alkyl, CF3, (C1-10)alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, cyano, nitro, hydroxy, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.
43. The compound according to claims 41 or 42 wherein R7 is independently selected from the group consisting of -cyano, -methoxy, -nitro, -carboxy, -sulfonamido, -tetrazolyl, -aminomethyl, -hydroxymethyl, -phenyl, -halo, -CONH2, -CONH(C1-7)alkyl, -CO2(C1-7)alkyl, -NH2, -OH, -(C1-5)alkyl, -alkenyl, -alkynyl, (C1-5)cycloalkyl, aryl, heteroaryl, and heterocycloalkyl, each substituted or unsubstituted.
44. A compound according to claim 29 comprising:

wherein m is 0,1,2,3,4 or 5;
n is 1, 2, or 3;
Q1 and Q2 are each independently selected from the group consisting of CO, CS, SO, SO2, and C=NR9;
R1 is hydrogen or is selected from the group consisting of halo, perhalo(C1-10)alkyl, amino, cyano, thio, (C1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;
R2 is hydrogen or selected from the group consisting of (C1-10)alkyl, (C3-12)cycloalkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-12)bicycloaryl, hetero(C4-12)bicycloaryl(C1-5)alkyl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;
R3 is selected from the group consisting of perhalo(C1-10)alkyl, amino, (C1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted, and a substituted or unsubstituted 3, 4, 5, 6 or 7 membered ring;
each R5 and R6 is independently hydrogen or is selected from the group consisting of a substituted or unsubstituted (C1-10)alkyl, a substituted or unsubstituted (C1-10)alkoxy, cyano, and halo, or where R5 and R6 are taken together to form a ring;

each R7 is independently selected from the group consisting of halo, perhalo(C1-10)alkyl, CF3, (C1-10)alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, cyano, nitro, hydroxy, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted; and R9 is hydrogen or is selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, bicycloaryl, and heterobicycloaryl, each substituted or unsubstituted.
45. A compound according to claim 29 comprising:
a member selected from the group consisting of wherein n is 1, 2, or 3;
Q1 and Q2 are each independently selected from the group consisting of CO, CS, SO, SO2, and C=NR9;
each of T, U, V, W and Y is independently nitrogen or CR16, provided that no more than two of T, U, V, W and Y are nitrogen;
R1 is hydrogen or is selected from the group consisting of halo, perhalo(C1-10)alkyl, amino, cyano, thin, (C1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;
R2 is hydrogen or selected from the group consisting of (C1-10)alkyl, (C3-12)cycloalkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-12)bicycloaryl, hetero(C4-12)bicycloaryl(C1-5)alkyl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;
R3 is selected from the group consisting of perhalo(C1-10)alkyl, amino, (C1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted, and a substituted or unsubstituted 3, 4, 5, 6 or 7 membered ring;
each R5 and R6 is independently hydrogen or is selected from the group consisting of a substituted or unsubstituted (C1-10)alkyl, a substituted or unsubstituted (C1-10)alkoxy, cyano, and halo, or where R5 and R6 are taken together to form a ring;
R9 is hydrogen or is selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, bicycloaryl, and heterobicycloaryl, each substituted or unsubstituted; and each R16 is independently selected from the group consisting of halo, perhalo(C1-10)alkyl, CF3, (C1-10)alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, cyano, nitro, hydroxy, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.
46. The compound according to any one of claims 1-45 wherein R3 is selected from the group consisting of amino, (C1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, and heteroaryl, each substituted or unsubstituted, and a substituted or unsubstituted 3, 4, 5, 6 or 7 membered ring.
47. The compound according to any one of claims 1-45 wherein R3 comprises the formula wherein R10 and R11 are each independently selected from the group consisting of hydrogen, perhalo(C1-10)alkyl, amino, (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl (C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-12)bicycloaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, and sulfinyl group, each substituted or unsubstituted, or R10 and R11 are taken together to form a 4, 5, 6, or 7 membered ring, each substituted or unsubstituted.
48. The compound according to any one of claims 1-45 wherein R3 is a substituted or unsubstituted 3, 4, 5, 6, or 7 membered ring.
49. The compound according to any one of claims 1-45 wherein R3 is a substituted or unsubstituted 3, 4, 5, 6, or 7 membered cycloalkyl.
50. The compound according to any one of claims 1-45 wherein R3 is a substituted or unsubstituted 4, 5, 6, or 7 membered heterocycloalkyl.
51. The compound according to any one of claims 1-45 wherein R3 is a substituted or unsubstituted aryl.
52. The compound according to any one of claims 1-45 wherein R3 is a substituted or unsubstituted heteroaryl.
53. The compound according to any one of claims 1-45 wherein R3 is selected from the group consisting of wherein p is 0-12 and each R8 is independently selected from the group consisting of halo, perhalo(C1-10)alkyl, CF3, cyano, nitro, hydroxy, alkyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thin, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.
54. The compound according to any one of claims 1-45 wherein R3 is selected from the group consisting of wherein r is 0-13 and each R8 is independently selected from the group consisting of halo, perhalo(C1-10)alkyl, CF3, cyano, nitro, hydroxy, alkyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.
55. The compound according to any one of claims 1-45, wherein R3 is a substituted or unsubstituted heteroaryl selected from the group consisting of furan, thiophene, pyrrole, pyrazole, triazole, isoxazole, oxazole, thiazole, isothiazole, oxadiazole, pyridine, pyridazine, pyrimidine, pyrazine, triazine, benzofuran, isobenzofuran, benzothiophene, isobenzothiophene, imidazole, benzimidazole, indole, isoindole, quinoline, isoquinoline, cinnoline, quinazoline, naphthyridine, pyridopyridine, quinoxaline, phthalazine, and benzothiazole, each substituted or unsubstituted.
56. The compound according to any one of claims 1-45, wherein R3 is selected from the group consisting of (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl (C1-5)alkyl, (C9-12)bicycloaryl, and hetero(C4-12)bicycloaryl, each substituted or unsubstituted.
57. The compound according to any one of claims 1-45, wherein R3 is a substituted or unsubstituted (C3-7)cycloalkyl ring, optionally comprising O, N(O), N, S, SO, SO2 or a carbonyl group in the ring.

58. The compound according to any one of claims 1-57 wherein R3 is substituted such that R3 comprises a substituent selected from the group consisting of a primary, secondary or tertiary amine, a heterocycloalkyl comprising a nitrogen ring atom, and a heteroaryl comprising a nitrogen ring atom.
59. The compound according to any one of claims 1-57 wherein R3 comprises a basic nitrogen atom that is capable of interacting with a carboxylic acid side chain of an active site residue of a protein.
60. The compound of claim 59 wherein the basic nitrogen of R3 is separated from the ring atom to which R3 is attached by between 1-5 atoms.
61. The compound of claim 59 wherein the basic nitrogen atom forms part of a primary, secondary or tertiary amine.
62. The compound of claim 59 wherein the basic nitrogen atom is a nitrogen ring atom of a heterocycloalkyl or a heteroaryl.
63. The compound according to claim 53 or 54 wherein at least one R8 comprises a basic nitrogen atom that is capable of interacting with a carboxylic acid side chain of an active site residue of a protein.
64. The compound of claim 63 wherein the basic nitrogen atom forms part of a primary, secondary or tertiary amine.
65. The compound of claim 63 wherein the basic nitrogen atom is a nitrogen ring atom of a heterocycloalkyl comprising a nitrogen ring atom or a heteroaryl comprising a nitrogen ring atom.
66. The compound according to claim 53 or 54 wherein at least one R8 is a primary, secondary or tertiary amine.

67. The compound according to claim 53 or 54 wherein at least one R8 is a substituted or unsubstituted heterocycloalkyl comprising a nitrogen ring atom or a substituted or unsubstituted heteroaryl comprising a nitrogen ring atom.
68. The compound according to claim 53 or 54 wherein at least one R8 is selected from the group consisting of -NH2, -NH(C1-5 alkyl), -N(C1-5 alkyl) 2, piperazine, imidazole, and pyridine.
69. The compound according to any one of claims 1-45, wherein R3 is selected from the group consisting of 3-amino-piperidinyl-1-yl, 3-aminomethyl-pyrrolidin-1-yl, 3-aminoazetidin-1-yl, 3-amino-3-methylpiperidin-1-yl, 3-aminocyclopent-1-yl, 3-aminomethylcyclopent-1-yl, 3-aminomethylcyclohex-1-yl, 3-aminohexahydroazepin-1-yl, 3-amino-cyclohex-1-yl, piperazin-1-yl, homopiperazin-1-yl, 3-amino-pyrrolidin-1-yl, R-3-aminopiperidin-1-yl, R-3-amino-3-methylpiperidin-1-yl, 3-amino-cyclohex-1-yl, 3-amino-cyclopent-1-yl, and 3-amino-pyrrolidin-1-yl, each substituted or unsubstituted.
70. The compound according to any one of claims 1, 2, 4-22, and 23-69, wherein at least one of Q1 and Q2 is CO.
71. The compound according to any one of claims 1, 2, 4-22, and 23-69, wherein Q1 and Q2 are CO.
72. The compound according to any one of claims 1-20, wherein M is nitrogen.
73. The compound according to any one of claims 1-20, wherein M is CR4 and where R4 is selected from the group consisting of wherein A is S, O or NR24;
B is CR23 or N;
R23 is independently selected from the group consisting of hydrogen, halo, perhalo(C1-10)alkyl, amino, thio, cyano, CF3, nitro, (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, -aryl(C1-10)alkyl, heteroaryl (C1-5)alkyl, (C9-12)bicycloaryl, hetero(C$-12)bicycloaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, imino group, carbonyl group, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, and sulfinyl group, each substituted or unsubstituted; and R23 is independently selected from the group consisting of hydrogen, perhalo(C1-10)alkyl, amino, (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, aryl(C1-lo)alkyl, heteroaryl (C1-5)alkyl, (C9-12)bicycloaryl, hetero(C8-12)bicycloaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, imino group, carbonyl group, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, and sulfinyl group, each substituted or unsubstituted.
74. The compound according to any one of claims 1-20, wherein M is CR4 and where R4 is selected from the group consisting of wherein u is 0, 1, 2, 3, 4, or 5; and each R18 is independently selected from the group consisting of halo, perhalo(C1-10)alkyl, CF3, (C1-10)alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, cyano, nitro, hydroxy, alkoxy, carbonyl group, imine group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

75. The compound according to any one of claims 1-20, wherein M is CR4 and where R4 is selected from the group consisting of wherein s is 0, 1, 2, or 3; and each R7 is independently selected from the group consisting of halo, perhalo(C1-10)alkyl, CF3, (C1-10)alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, cyano, nitro, hydroxy, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.
76. The compound according to any one of claims 10, 19, 20, 29, 44 and 45, wherein R5 and R6 are hydrogen.
77. The compound according to any one of claims 10, 19, 20, 29, 44 and 45, wherein R5 and R6 are halogen.
78. The compound according to any one of claims 10, 19, 20, 29, 44 and 45, wherein R5 and R6 are taken together to form a ring.
79. The compound according to any one of claims 10, 19, 20, 29, 44 and 45, wherein at least one of R5 and R6 is a substituted or unsubstituted -(C1-8)alkyleneR13, wherein R13 is selected from the group consisting of (C3-12)cycloalkyl, hetero(C4-12)cycloalkyl, (C6-12)aryl, hetero(C5-12)aryl, (C9-12)bicycloalkyl, hetero(C9-12)bicycloalkyl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl, each substituted or unsubstituted.
80. The compound according to any one of claims 19 and 44, wherein R5 and R6 are hydrogen, m is 1 or 2, and each R7 is independently selected from the group consisting of halo, perhalo(C1-10)alkyl, CF3, cyano, nitro, hydroxy, alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thin, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.
81. The compound according to any one of claims 19 and 44, wherein two R7 are taken together to form a substituted or unsubstituted fused or bridged ring.
82. The compound according to any one of claims 10, 19, 20, 29, 44 and 45, wherein:
n is 1, 2 or 3; and R5 and R6 are hydrogen.
83. The compound according to any one of claims 10, 19, 20, 29, 44 and 45, wherein:
n is 1 or 2;
R3 is selected from the group consisting of amino, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, and a substituted or unsubstituted 4, 5, 6 or 7 membered ring; and R5 and R6 are hydrogen.
84. The compound according to any one of claims 19 and 44, wherein: R5 and R6 are hydrogen and R7 is 2-cyano.
85. The compound of claim 84, wherein n is 1.
86. The compound according to any one of claims 10, 19, 20, 29, 44 and 45, wherein:
n is 1, 2 or 3;
R5 and R6 are hydrogen; and R3 is selected from the group consisting of (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl (C1-5)alkyl, (C9-12)bicycloaryl, and hetero(C4-12)bicycloaryl, each substituted or unsubstituted.

87. The compound according to any one of claims 19 and 44, wherein:
n is 1,2 or 3;
R5 and R6 are hydrogen; and each R7 is independently selected from the group consisting of halo, perhalo(C1-10)alkyl, alkenyl, alkynyl, CF3, cyano, nitro, hydroxy, heteroaryl, aryloxy, heteroaryloxy, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

88. The compound according to any one of claims 16, 17, 19 and 41-44, wherein:
two R7 are taken together to form a substituted or unsubstituted fused ring.

89. The compound according to any one of claims 16, 17, 19 and 41-44, wherein:
two R7 are taken together to form a substituted or unsubstituted bridged ring.

90. The compound according to any one of claims 20 and 45, wherein two of T, U, V, W
and Y are taken together and substituted through available valencies to form a substituted or unsubstituted ring fused or bridged to the ring formed by T U, V, W and Y.

91. The compound according to any one of claims 1-90, wherein R2 is a substituted or unsubstituted (C1-10)alkyl.

92. The compound according to any one of claims 1-90, wherein R2 is a substituted or unsubstituted (C1-4)alkyl.

93. The compound according to any one of claims 1-90, wherein R2 is -Y-Z
wherein Y a linker providing 1, 2 or 3 atom separation between Z and the ring to which Y is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur; and Z is hydrogen or selected from the group consisting of (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-12)bicycloaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, alkenyl, alkynyl, carbonyl group, cyano, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

94. The compound according to any one of claims 1-90, wherein R2 is selected from the group consisting of wherein A is S, O or NR24;
B is CR23 or N;
R23 is independently selected from the group consisting of hydrogen, halo, perhalo(C1-10)alkyl, amino, thio, cyano, CF3, nitro, (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl (C1-5)alkyl, (C9-l2)bicycloaryl, hetero(C8-12)bicycloaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, imino group, carbonyl group, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, and sulfinyl group, each substituted or unsubstituted; and R24 is independently selected from the group consisting of hydrogen, perhalo(C1-10)alkyl, amino, (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl (C1-5)alkyl, (C9-12)bicycloaryl, hetero(C8-12)bicycloaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, imino group, carbonyl group, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, and sulfinyl group, each substituted or unsubstituted.

95. The compound according to any one of claims 1-90, wherein R2 is selected from the group consisting of wherein t is 0, 1, 2, 3, 4, or 5; and each R18 is independently selected from the group consisting of halo, perhalo(C1-10)alkyl, CF3, (C1-10)alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thin, cyano, nitro, hydroxy, alkoxy, carbonyl group, imine group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

96. A compound according to any one of claims 1-95 selected from the group consisting of:
2-(6-Chloro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl)-benzonitrile;
2-(6-Chloro-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl)-benzonitrile;
2-{6-[3-Amino-piperidin-1-yl]-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;
2-{6-[3-Amino-piperidin-1-yl]-3-ethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;
2-{6-[3-Amino-piperidin-1-yl]-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;
2-{6-[3-Amino-piperidin-1-yl]-5-chloro-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;
6-[3-Amino-piperidin-1-yl]-1-(2-bromo-benzyl)-1H-pyrimidine-2,4-dione;
6-[3-Amino-piperidin-1-yl]-1-(2-iodo-benzyl)-1H-pyrimidine-2,4-dione;
6-[3-Amino-piperidin-1-yl]-1-(2-bromo-5-fluoro-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;
6-[3-Amino-piperidin-1-yl]-1-(2-chloro-5-fluoro-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;
6-[3-Amino-piperidin-1-yl]-1-(2-chloro-4-fluoro-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;
6-[3-Amino-piperidin-1-yl]-1-(2-bromo-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;

2-{6-[Azepan-3(~)-ylamino]-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile (14);
2-{6-[3(~)-Amino-azepan-1-yl]-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

2-[6-(2-Amino-ethylamino)-3-ethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-benzonitrile;

2-{6-[3-Amino-piperidin-1-yl]-3-(3-cyano-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl} -benzonitrile;

2-{6-[3-Amino-piperidin-1-yl]-3-(2-cyano-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

2-{6-[3-Amino-piperidin-1-yl]-3-(4-cyano-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

2-[6-(3-Amino-piperidin-1-yl)-3-(1H-benzoimidazol-2-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-benzonitrile;

2-{6-[3-Amino-piperidin-1-yl]-2,4-dioxo-3-(4-pyrazol-1-yl-benzyl)-3,4-dihydro-2H-pyrimidin-1-ylmethyl} -benzonitrile;

2-{6-[3-Amino-piperidin-1-yl]-2,4-dioxo-3-(3-pyrrol-1-yl-benzyl)-3,4-dihydro-pyrimidin-1-ylmethyl}-benzonitrile;

6-[3-Amino-piperidin-1-yl]-3-(2-cyano-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ylmethyl]-thiophene-3-carbonitrile;

3-{4-[3-Amino-piperidin-1-yl]-3-(2-cyano-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ylmethyl}-benzoic acid methyl ester;

3-{4-[3-Amino-piperidin-1-yl]-3-(2-cyano-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ylmethyl}-benzoic acid;

6-[3-Amino-piperidin-1-yl]-1,3-bis-(2-bromo-5-fluoro-benzyl)-1H-pyrimidine-2,4-dione;

2-{6-[3(R)-Amino-piperidin-1-yl]-5-chloro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

6-[3(R)-Amino-piperidin-1-yl]-1-(2,5-di-chloro-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;

6-[3(R)-Amino-piperidin-1-yl]-1-(2-chloro-3,6-di-fluoro-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;

(R)-2-((6-(3-amino-3-methylpiperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)-4-fluorobenzonitrile; and 2-[6-(3-Amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-4-fluoro-benzonitrile.

97. A compound according to any one of claims 1-95 selected from the group consisting of:

2-{6-[3 (R)-Amino-piperidin-1-yl]-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

2-{6-[3(R)-Amino-piperidin-1-yl]-3-ethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

2-{6-[3(R)-Amino-piperidin-1-yl]-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

2-{6-[3(R)-Amino-piperidin-1-yl]-5-chloro-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

6-[3(R)-Amino-piperidin-1-yl]-1-(2-bromo-benzyl)-1H-pyrimidine-2,4-dione;

6-[3(R)-Amino-piperidin-1-yl]-1-(2-iodo-benzyl)-1H-pyrimidine-2,4-dione;

6-[3(R)-Amino-piperidin-1-yl]-1-(2-bromo-5-fluoro-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;

6-[3(R)-Amino-piperidin-1-yl]-1-(2-chloro-5-fluoro-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;

6-[3(R)-Amino-piperidin-1-yl]-1-(2-chloro-4-fluoro-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;

6-[3(R)-Amino-piperidin-1-yl]-1-(2-bromo-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;

2-{6-[3(R)-Amino-piperidin-1-yl]-3-(3-cyano-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

2-{6-[3(R)-Amino-piperidin-1-yl]-3-(2-cyano-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

2-{6-[3(R)-Amino-piperidin-1-yl]-3-(4-cyano-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

2-[6-(3-Amino-piperidin-1-yl)-3-(1H-benzoimidazol-2-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-benzonitrile 2-{6-[3(R)-Amino-piperidin-1-yl]-2,4-dioxo-3-(4-pyrazol-1-yl-benzyl)-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

2-{6-[3(R)-Amino-piperidin-1-yl]-2,4-dioxo-3-(3-pyrrol-1-yl-benzyl)-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

6-[3(R)-Amino-piperidin-1-yl]-3-(2-cyano-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ylmethyl]-thiophene-3-carbonitrile;

3-{4-[3(R)-Amino-piperidin-1-yl]-3-(2-cyano-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ylmethyl}-benzoic acid methyl ester;

3-{4-[3(R)-Amino-piperidin-1-yl]-3-(2-cyano-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ylmethyl}-benzoic acid;

6-[3(R)-Amino-piperidin-1-yl]-1,3-bis-(2-bromo-5-fluoro-benzyl)-1H-pyrimidine-2,4-dione; and 2-[6-(3(R)-Amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-4-fluoro-benzonitrile.

98. The compound according to any one of claims 1-97, wherein the compound is in the form of a pharmaceutically acceptable salt.

99. The compound according to any one of claims 1-98, wherein the compound is present in a mixture of stereoisomers.

100. The compound according to any one of claims 1-98, wherein the compound comprises a single stereoisomer.

101. A pharmaceutical composition comprising, as an active ingredient, a compound according to any one of claims 1-100.

102. The pharmaceutical composition according to claim 101, wherein the composition is a solid formulation adapted for oral administration.

103. The pharmaceutical composition according to claim 101, wherein the composition is a tablet.

104. The pharmaceutical composition according to claim 101, wherein the composition is a liquid formulation adapted for oral administration.

105. The pharmaceutical composition according to claim 101, wherein the composition is a liquid formulation adapted for parenteral administration.

106. The pharmaceutical composition comprising a compound according to any one of claims 1-100, wherein the composition is adapted for administration by a route selected from the group consisting of orally, parenterally, intraperitoneally, intravenously, intraarterially, transdermally, sublingually, intramuscularly, rectally, transbuccally, intranasally, liposomally, via inhalation, vaginally, intraoccularly, via local delivery (for example by catheter or stent), subcutaneously, intraadiposally, intraarticularly, and intrathecally.

107. A kit comprising:

a compound according to any one of claims 1-100 or a composition according to any one of claims 101-106; and instructions which comprise one or more forms of information selected from the group consisting of indicating a disease state for which the compound is to be administered, storage information for the compound, dosing information and instructions regarding how to administer the compound.

108. The kit according to claim 107, wherein the kit comprises the compound in a multiple dose form.

109. An article of manufacture comprising:

a compound according to any one of claims 1-100; and packaging materials.

110. The article of manufacture of claim 109, wherein the packaging material comprises a container for housing the compound.

111. The article of manufacture of claim 110, wherein the container comprises a label indicating one or more members of the group consisting of a disease state for which the compound is to be administered, storage information, dosing information and/or instructions regarding how to administer the composition.

112. The article of manufacture of claim 109, wherein the article of manufacture comprises the compound in a multiple dose form.

113. A method of inhibiting DPP-IV comprising:

contacting DPP-IV with a compound according to any one of claims 1-100.

114. A method of inhibiting DPP-IV comprising:

causing a compound according to any one of claims 1-100 to be present in a subject in order to inhibit DPP-IV in vivo.

115. A method of inhibiting DPP-IV comprising:

administering a first compound to a subject that is converted in vivo to a second compound wherein the second compound inhibits DPP-IV in vivo, the second compound being a compound according to any one of claims 1-100.

116. A therapeutic method comprising:

administering a compound according to any one of claims 1-100 to a subject.

117. A method of treating a disease state for which DPP-IV possesses activity that contributes to the pathology and/or symptomology of the disease state, the method comprising causing a compound according to any one of claims 1-100 to be present in a subject in a therapeutically effective amount for the disease state.

118. The method according to claim 117, wherein the disease is type I or type II
diabetes.

119. A method of treating cancer in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a compound according to any one of claims 1-100.

120. The method of claim 119, wherein the cancer treated is colorectal, prostate, breast, thyroid, skin, lung, or head and neck.

121. A method of treating autoimmune disorders such as, but not limited to, rheumatoid arthritis, psoriasis, and multiple sclerosis in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a compound according to any one of claims 1-100.

122. A method of treating HIV infection in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a compound according to any one of claims 1-100.

123. A method of treating a condition characterized by inadequate lymphocyte or hemapoietic cell activation or concentration in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a compound according to any one of claims 1-100.

123. The method of claim 123, wherein said condition is a side effect of chemotherapy or radiation therapy.

125. The method of claim 123, wherein said condition is a result of kidney failure.

126. The method of claim 123, wherein said condition is a result of a bone marrow disorder.

127. A method of treating a condition characterized by immunodeficiency symptoms in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a compound according to any one of claims 1-100.

128. A process for producing a pyrimidin-dione of the formula:

wherein M is N or CR4;

R2 is hydrogen or selected from the group consisting of (C1-10)alkyl, (C3-12)cycloalkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-12)bicycloaryl, hetero(C4-12)bicycloaryl(C1-5)alkyl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;

R3 is selected from the group consisting of perhalo(C1-10)alkyl, amino, (C1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted, and a substituted or unsubstituted 3, 4, 5, 6 or 7 membered ring;

R4 is hydrogen or is selected from the group consisting of halo, perhalo(C1-10)alkyl, amino, cyano, thio, (C1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;

L is a linker providing 1, 2 or 3 atom separation between X and the ring to which L
is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur; and X is selected from the group consisting of (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-12)bicycloaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, alkenyl, alkynyl, carbonyl group, cyano, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;

the process comprising the steps of:

(i) contacting a compound of the formula A

wherein Hal is halogen;

with a compound of the formula B

X~L~LG B

wherein LG is a leaving group;

L is a linker providing 1, 2 or 3 atom separation between X and the ring to which L is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur; and X is selected from the group consisting of (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-12)bicycloaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, alkenyl, alkynyl, carbonyl group, cyano, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;

under conditions sufficient to produce a compound of the formula C

(ii) contacting the compound of formula C with a compound of formula D

R2~LG' D

wherein LG' is a leaving group;

under conditions sufficient to produce a compound of the formula E;

wherein R2 is selected from the group consisting of (C1-10)alkyl, (C3-12)cycloalkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-12)bicycloaryl, hetero(C4-12)bicycloaryl(C1-5)alkyl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted; and (iii) contacting the compound of formula E with a compound of formula R3-H under conditions sufficient to produce the pyrimidin-dione.

129. The process of Claim 128, wherein the pyrimidin-dione product is further converted to an acid addition salt.

130. The process of Claim 129, wherein the acid addition salt is selected from the group consisting of acetate, citrate, hydrochloride, L-lactate, succinate, sulfate, p-toluenesulfonate, benzenesulfonate, benzoate, methanesulfonate, naphthylene-2-sulfonate, propionate, p-toluenesulfonate, hydrobromate, hydroiodate, R-mandelate, and L-tartrate.

131. The process of Claim 128, wherein Hal is selected from the group consisting of Br, Cl and F in the compound of formula A.

132. The process of Claim 128, wherein the leaving group LG is selected from the group consisting of Br, Cl and I.

133. The process of Claim 128, wherein step (ii) further comprises the addition of a base.

134. The process of Claim 133, wherein the base is potassium carbonate.

135. The process of Claim 128, wherein product E is further purified before subjecting to step (iii).

136. The process of Claim 135, wherein the purification of product E is performed by solvent washes and/or by chromatography.

137. The process of Claim 128, wherein R3-H is a secondary amine or an amine hydrochloride.

138. The process of Claim 128, wherein R3-H is selected from the group consisting of ~
wherein p is 0-12 and each R8 is independently selected from the group consisting of halo, perhalo(C1-10)alkyl, CF3, cyano, nitro, hydroxy, alkyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted, or the mono- or di-hydrochloride salt.

139. The process of Claim 128, wherein step iii) further comprises a purification step of washing of the product with organic solvents or mixture of solvents and/or by column chromatography.

140. The process of Claim 128, wherein L is selected from the group consisting of -CH2-, -CH2CH2-, -CH2CH2CH2-, -C(O)-, -CH2C(O)-, -C(O)CH2-, -CH2-C(O)CH2-, -C(O)CH2CH2-, -CH2CH2C(O)-, -O-, -OCH2-, -CH2O-, -CH2OCH2-, -OCH2CH2-, -CH2CH2O-, -N(CH3)-, -NHCH2-, -CH2NH-, -CH2NHCH2-, -NHCH2CH2-, -CH2CH2NH-, -NH-C(O)-, -NCH3-C(O)-, -C(O)NH-, -C(O)NCH3-, -NHC(O)CH2-, -C(O)NHCH2-, -C(O)CH2NH-, -CH2NHC(O)-, -CH2C(O)NH-, -NHCH2C(O)-, -S-, -SCH2-, -CH2S-, -SCH2CH2-, -CH2SCH2-, -CH2CH2S-, -C(O)S-, -C(O)SCH2-, -CH2C(O)S-, -C(O)CH2S-, and -CH2SC(O)-, each substituted or unsubstituted.

141. The process of Claim 140, wherein L is selected from the group consisting of -CH2-, -C(O)-, -CH2C(O)-, -C(O)CH2-, -CH2-C(O)CH2-, -C(O)CH2CH2-, and -CH2CH2C(O)-, each substituted or unsubstituted.

142. The process of Claim 128, wherein -L-X taken together is selected from the group consisting of -(CH2)-(2-cyano)phenyl; -(CH2)-(3-cyano)phenyl; -(CH2)-(2-hydroxy)phenyl;
-(CH2)-(3-hydroxy)phenyl; -(CH2)-(2-alkenyl)phenyl; -(CH2)-(3-alkenyl)phenyl; -(CH2)-(2-alkynyl)phenyl; -(CH2)-(3-alkynyl)phenyl; -(CH2)-(2-methoxy)phenyl; -(CH2)-(3-methoxy)phenyl; -(CH2)-(2-nitro)phenyl; -(CH2)-(3-nitro)phenyl; -(CH2)-(2-carboxy)phenyl; -(CH2)-(3-carboxy)phenyl; -(CH2)-(2-carboxamido)phenyl; -(CH2)-(3-carboxamido)phenyl; -(CH2)-(2-sulfonamido)phenyl; -(CH2)-(3-sulfonamido)phenyl; -(CH2)-(2-tetrazolyl)phenyl; -(CH2)-(3-tetrazolyl)phenyl; -(CH2)-(2-aminomethyl)phenyl; -(CH2)-(3-aminomethyl)phenyl; -(CH2)-(2-hydroxymethyl)phenyl; -(CH2)-(3-hydroxymethyl)phenyl; -(CH2)-(2-phenyl)phenyl; -(CH2)-(3-phenyl)phenyl; -(CH2)-(2-halo)phenyl; -(CH2)-(3-halo)phenyl; -(CH2)-(2-CONH2)phenyl; -(CH2)-(3-CONH2)phenyl;
-(CH2)-(2-CONH(C1-7)alkyl)phenyl; -(CH2)-(3-CONH(C1-7)alkyl)phenyl; -(CH2)-(2-CO2(C1-7)alkyl)phenyl; -(CH2)-(3-CO2(C1-7)alkyl)phenyl; -(CH2)-(2-NH2)phenyl; -(CH2)-(3-NH2)phenyl; -(CH2)-(2-(C3-7)alkyl)phenyl; -(CH2)-(3-(C3-7)alkyl)phenyl; -(CH2)-(2-(C3-7)cycloalkyl)phenyl; -(CH2)-(3-(C3-7)cycloalkyl)phenyl; -(CH2)-(2-aryl)phenyl; -(CH2)-(3-aryl)phenyl; -(CH2)-(2-heteroaryl)phenyl; -(CH2)-(3-heteroaryl)phenyl; -(CH2)-2-bromo-5-fluoro phenyl; -(CH2)-2-chloro-5-fluoro phenyl; -(CH2)-2-cyano-5-fluoro phenyl;
-(CH2)-2,5-dichloro phenyl; -(CH2)-2,5-difluoro phenyl; -(CH2)-2,5-dibromo phenyl; -(CH2)-2-bromo-3,5-difluoro phenyl; -(CH2)-2-chloro-3,5-difluoro phenyl; -(CH2)-2,3,5-trifluoro phenyl; -(CH2)-2,3,5,6-tetrafluorophenyl; -(CH2)-2-bromo-3,5,6-trifluoro phenyl;
-(CH2)-2-chloro-3,5,6-trifluoro phenyl; -(CH2)-2-cyano-3,5-difluoro phenyl; -(CH2)-2-cyano-3,5,6-trifluoro phenyl; -(CH2)-(2-heterocycloalkyl)phenyl; and -(CH2)-(3-heterocycloalkyl)phenyl, each substituted or unsubstituted.
143. The process of Claim 128, wherein M is CH, and R3 comprises the formula wherein R10 and R11 are each independently selected from the group consisting of hydrogen, perhalo(C1-10)alkyl, amino, (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl (C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-i2)bicycloaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, and sulfinyl group, each substituted or unsubstituted, or R10 and R11 are taken together to form a 4, 5, 6, or 7 membered ring, each substituted or unsubstituted.

144. The process of Claim 128, wherein M is CH, and wherein R3 is selected from the group consisting of 3-amino-piperidinyl-1-yl, 3-aminomethyl-pyrrolidin-1-yl, 2-aminoazetidin-1-yl, 3-amino-3-methylpiperidin-1-yl, 3-aminocyclopent-1-yl, 3-aminomethylcyclopent-1-yl, 3-aminomethylcyclohex-1-yl, 3-aminohexahydroazepin-1-yl, 3-amino-cyclohex-1-yl, piperazin-1-yl, homopiperazin-1-yl, 3-amino-pyrrolidin-1-yl, R-3-aminopiperidin-1-yl, R-3-amino-3-methylpiperidin-1-yl, 3-amino-cyclohex-1-yl, 3-amino-cyclopent-1-yl, and 3-amino-pyrrolidin-1-yl, each substituted or unsubstituted.
145. The process of Claim 128, wherein M is CH, and wherein R2 is a substituted or unsubstituted (C1-10)alkyl.
146. The process of claim 128 for producing a pyrimidin-dione of the formula comprising:
(i) admixing 6-chloro-1H-pyrimidine-2,4-dione with an aryl halide of the formula where Hal is Br, Cl, or I, under condition sufficient to produce a compound of the formula (ii) alkylating the above product with a methyl halide under conditions sufficient to form a compound of the formula ~; and (iii) condensing the above product with a compound of the formula 147. ~The process for producing a pyrimidin-dione of Claim 146, further comprising the formation of the acid addition salt.

148. ~The process of Claim 147, wherein the acid addition salt is the benzoate salt.

149. ~The process of claim 128 wherein the pyrimidin-dione is selected from the group consisting of:
2-(6-Chloro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl)-benzonitrile;~
2-(6-Chloro-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl)-benzonitrile;
2-{6-[3-Amino-piperidin-1-yl]-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;
2-{6-[3-Amino-piperidin-1-yl]-3-ethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;
2-{6-[3-Amino-piperidin-1-yl]-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;
2-{6-[3-Amino-piperidin-1-yl]-5-chloro-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;
6-[3-Amino-piperidin-1-yl]-1-(2-bromo-benzyl)-1H-pyrimidine-2,4-dione;

6-[3-Amino-piperidin-1-yl]-1-(2-iodo-benzyl)-1H-pyrimidine-2,4-dione;
6-[3-Amino-piperidin-1-yl]-1-(2-bromo-5-fluoro-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;
6-[3-Amino-piperidin-1-yl]-1-(2-chloro-5-fluoro- benzyl)-3-methyl-1H-pyrimidine-2,4-dione;
6-[3-Amino-piperidin-1-yl]-1-(2-chloro-4-fluoro-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;
6-[3-Amino-piperidin-1-yl]-1-(2-bromo-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;
2-{6-[Azepan-3 (~)-ylamino]-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile (14);
2-{6-[3(~)-Amino-azepan-1-yl]-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl} -benzonitrile;
2-[6-(2-Amino-ethylamino)-3-ethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-benzonitrile;
2-{6-[3-Amino-piperidin-1-yl]-3-(3-cyano-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;
2-{6-[3-Amino-piperidin-1-yl]-3-(2-cyano-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;
2-{6-[3-Amino-piperidin-1-yl]-3-(4-cyano-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;
2-[6-(3-Amino-piperidin-1-yl)-3-(1H-benzoimidazol-2-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-benzonitrile;
2-{6-[3-Amino-piperidin-1-yl]-2,4-dioxo-3-(4-pyrazol-1-yl-benzyl)-3,4-dihydro-2H-pyrimidin-1-ylmethyl} -benzonitrile;
2-{6-[3-Amino-piperidin-1-yl]-2,4-dioxo-3-(3-pyrrol-1-yl-benzyl)-3,4-dihydro-pyrimidin-1-ylmethyl}-benzonitrile;
6-[3-Amino-piperidin-1-yl]-3-(2-cyano-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ylmethyl]-thiophene-3-carbonitrile;
3-{4-[3-Amino-piperidin-1-yl]-3-(2-cyano-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ylmethyl}-benzoic acid methyl ester;

3-{4-[3-Amino-piperidin-1-yl]-3-(2-cyano-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ylmethyl}-benzoic acid;
2-{6-[3(R)-Amino-piperidin-1-yl]-5-chloro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;
6-[3(R)-Amino-piperidin-1-yl]-1-(2,5-di-chloro-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;
6-[3(R)-Amino-piperidin-1-yl]-1-(2-chloro-3,6-di-fluoro-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;
(R)-2-((6-(3-amino-3-methylpiperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)-4-fluorobenzonitrile; and 6-[3-Amino-piperidin-1-yl]-1,3-bis-(2-bromo-5-fluoro-benzyl)-1H-pyrimidine-2,4-dione.
150. The process of claim 128, wherein the pyrimidin-dione is selected from the group consisting of:
2-{6-[3(R)-Amino-piperidin-1-yl]-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;
2-{6-[3(R)-Amino-piperidin-1-yl]-3-ethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;
2-{6-[3(R)-Amino-piperidin-1-yl]-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;
2-{6-[3(R)-Amino-piperidin-1-yl]-5-chloro-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;
6-[3(R)-Amino-piperidin-1-yl]-1-(2-bromo-benzyl)-1H-pyrimidine-2,4-dione;
6-[3(R)-Amino-piperidin-1-yl]-1-(2-iodo-benzyl)-1H-pyrimidine-2,4-dione;
6-[3(R)-Amino-piperidin-1-yl]-1-(2-bromo-5-fluoro-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;
6-[3(R)-Amino-piperidin-1-yl]-1-(2-chloro-5-fluoro-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;
6-[3(R)-Amino-piperidin-1-yl]-1-(2-chloro-4-fluoro-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;

6-[3(R)-Amino-piperidin-1-yl]-1-(2-bromo-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;
2-{6-[3(R)-Amino-piperidin-1-yl]-3-(3-cyano-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl }-benzonitrile;
2-{6-[3(R)-Amino-piperidin-1-yl]-3-(2-cyano-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl }-benzonitrile;
2-{6-[3(R)-Amino-piperidin-1-yl]-3-(4-cyano-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;
2-{6-[3(R)-Amino-piperidin-1-yl]-2,4-dioxo-3-(4-pyrazol-1-yl-benzyl)-3,4-dihydro-2H-pyrimidin-1-ylmethyl }-benzonitrile;
2-{6-[3(R)-Amino-piperidin-1-yl]-2,4-dioxo-3-(3-pyrrol-1-yl-benzyl)-3,4-dihydro-2H-pyrimidin-1-ylmethyl }-benzonitrile;
6-[3(R)-Amino-piperidin-1-yl]-3-(2-cyano-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ylmethyl]-thiophene-3-carbonitrile;
3-{4-[3(R)-Amino-piperidin-1-yl]-3-(2-cyano-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ylmethyl}-benzoic acid methyl ester;
3-{4-[3(R)-Amino-piperidin-1-yl]-3-(2-cyano-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ylmethyl}-benzoic acid; and 6-[3(R)-Amino-piperidin-1-yl]-1,3-bis-(2-bromo-5-fluoro-benzyl)-1H-pyrimidine-2,4-dione.
151. The process of claim 128, wherein the pyrimidin-dione is present in a mixture of stereoisomers.
152. The process of claim 128, wherein the pyrimidin-dione comprises a single stereoisomer.
153. A compound according to any one of claims 1-100 for use as a medicament.
154. Use of a compound according to any one of claims 1-100 in the manufacture of a medicament for inhibiting DPP-IV.

155. Use of a compound according to any one of claims 1-100 in the manufacture of a medicament for treating a disease state for which DPP-IV possess activity that contributes to the pathology and/or symptomology of the disease state.
156. Use of a compound according to any one of claims 1-100 in the manufacture of a medicament for treating cancer.
157. Use of a compound according to any one of claims 1-100 in the manufacture of a medicament for treating type I or type II diabetes.
158. Use of a compound according to any one of claims 1-100 in me manufacture of a medicament for treating autoimmune disorders.
159. Use of a compound according to any one of claims 1-100 in the manufacture of a medicament for treating a condition characterized by inadequate lymphocyte or hemapoietic cell activation or concentration.
160. Use of a compound according to any one of claims 1-100 in the manufacture of a medicament for treating HIV infection.
161. Use of a compound according to any one of claims 1-100 in the manufacture of a medicament for treating a condition characterized by immunodeficiency symptoms.
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Families Citing this family (146)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7407955B2 (en) 2002-08-21 2008-08-05 Boehringer Ingelheim Pharma Gmbh & Co., Kg 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
CN1894234A (en) 2003-03-25 2007-01-10 武田药品工业株式会社 Dipeptidyl peptidase inhibitors
MXPA06001601A (en) 2003-08-13 2006-08-25 Takeda Pharmaceutical 4-pyrimidone derivatives and their use as peptidyl peptidase inhibitors.
WO2005026148A1 (en) 2003-09-08 2005-03-24 Takeda San Diego, Inc. Dipeptidyl peptidase inhibitors
US20050065144A1 (en) * 2003-09-08 2005-03-24 Syrrx, Inc. Dipeptidyl peptidase inhibitors
US7501426B2 (en) 2004-02-18 2009-03-10 Boehringer Ingelheim International Gmbh 8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions
CN102079743B (en) 2004-03-15 2020-08-25 武田药品工业株式会社 Dipeptidyl peptidase inhibitors
US7931661B2 (en) * 2004-06-14 2011-04-26 Usgi Medical, Inc. Apparatus and methods for performing transluminal gastrointestinal procedures
DE102004054054A1 (en) 2004-11-05 2006-05-11 Boehringer Ingelheim Pharma Gmbh & Co. Kg Process for preparing chiral 8- (3-amino-piperidin-1-yl) -xanthines
WO2006068978A2 (en) 2004-12-21 2006-06-29 Takeda Pharmaceutial Company Limited Dipeptidyl peptidase inhibitors
DE102005035891A1 (en) 2005-07-30 2007-02-08 Boehringer Ingelheim Pharma Gmbh & Co. Kg 8- (3-amino-piperidin-1-yl) -xanthines, their preparation and their use as pharmaceuticals
PL1931350T5 (en) * 2005-09-14 2021-11-15 Takeda Pharmaceutical Company Limited Administration of dipeptidyl peptidase inhibitors
WO2007033350A1 (en) * 2005-09-14 2007-03-22 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors for treating diabetes
TW200745079A (en) * 2005-09-16 2007-12-16 Takeda Pharmaceuticals Co Polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile and methods of use therefor
EP1924567B1 (en) 2005-09-16 2012-08-22 Takeda Pharmaceutical Company Limited Process for the preparation of pyrimidinedione derivatives
WO2007074884A1 (en) * 2005-12-28 2007-07-05 Takeda Pharmaceutical Company Limited Therapeutic agent for diabetes
GB0526291D0 (en) 2005-12-23 2006-02-01 Prosidion Ltd Therapeutic method
UA95789C2 (en) * 2005-12-28 2011-09-12 Такеда Фармасьютикал Компани Лимитед Agent for the pancreas protection and use thereof
JP5452934B2 (en) * 2005-12-29 2014-03-26 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ Prokineticin 1 receptor antagonist
JP2009531456A (en) * 2006-03-28 2009-09-03 武田薬品工業株式会社 Preparation of (R) -3-aminopiperidine dihydrochloride
PE20071221A1 (en) 2006-04-11 2007-12-14 Arena Pharm Inc GPR119 RECEPTOR AGONISTS IN METHODS TO INCREASE BONE MASS AND TO TREAT OSTEOPOROSIS AND OTHER CONDITIONS CHARACTERIZED BY LOW BONE MASS, AND COMBINED THERAPY RELATED TO THESE AGONISTS
JP2009533393A (en) 2006-04-12 2009-09-17 プロビオドルグ エージー Enzyme inhibitor
KR101257378B1 (en) 2006-04-19 2013-04-23 삼진제약주식회사 Antiviral pyrimidinedione derivatives and method for the preparation thereof
EP1852108A1 (en) 2006-05-04 2007-11-07 Boehringer Ingelheim Pharma GmbH & Co.KG DPP IV inhibitor formulations
MX2008014024A (en) 2006-05-04 2008-11-14 Boehringer Ingelheim Int Polymorphs.
PE20080251A1 (en) 2006-05-04 2008-04-25 Boehringer Ingelheim Int USES OF DPP IV INHIBITORS
TWI394747B (en) 2006-06-23 2013-05-01 Smithkline Beecham Corp Prolyl hydroxylase inhibitors
RU2454220C2 (en) * 2006-08-16 2012-06-27 Новартис Аг Method for preparing solid dispersions of high crystalline therapeutic compounds
US20100179131A1 (en) 2006-09-07 2010-07-15 Nycomed Gmbh Combination treatment for diabetes mellitus
CA2663279C (en) * 2006-09-13 2016-05-17 Takeda Pharmaceutical Company Limited Use of 2-6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2h-pyrimidin-1-ylmethyl-4-fluoro-benzonitrile for treating diabetes, cancer, autoimmune disorders and hiv infection
US8324383B2 (en) 2006-09-13 2012-12-04 Takeda Pharmaceutical Company Limited Methods of making polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile
WO2008055945A1 (en) 2006-11-09 2008-05-15 Probiodrug Ag 3-hydr0xy-1,5-dihydr0-pyrr0l-2-one derivatives as inhibitors of glutaminyl cyclase for the treatment of ulcer, cancer and other diseases
TW200838536A (en) * 2006-11-29 2008-10-01 Takeda Pharmaceutical Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor
SI2091948T1 (en) 2006-11-30 2012-07-31 Probiodrug Ag Novel inhibitors of glutaminyl cyclase
EP2124901B1 (en) * 2007-02-01 2017-07-19 Takeda Pharmaceutical Company Limited Tablet preparation without causing a tableting trouble
ME01239B (en) 2007-02-01 2013-06-20 Takeda Pharmaceuticals Co Solid preparation comprising alogliptin and pioglitazone
US8093236B2 (en) 2007-03-13 2012-01-10 Takeda Pharmaceuticals Company Limited Weekly administration of dipeptidyl peptidase inhibitors
JP5432720B2 (en) * 2007-03-13 2014-03-05 武田薬品工業株式会社 2-[[6-[(3R) -3-Amino-1-piperidinyl] -3,4-dihydro-3-methyl-2,4-dioxo-1 (2H) -pyrimidinyl] methyl] -4-fluorobenzo Solid formulation containing nitrile
EP2143443B1 (en) 2007-04-03 2014-11-19 Mitsubishi Tanabe Pharma Corporation A combination of dipeptidyl peptidase iv inhibitor and sweetener for use in the treatment of obesity
DK2142514T3 (en) 2007-04-18 2015-03-23 Probiodrug Ag Thiourea derivatives as glutaminyl cyclase inhibitors
PT2152663E (en) 2007-06-04 2014-06-03 Univ Ben Gurion Tri-aryl compounds and compositions comprising the same
WO2009011451A1 (en) 2007-07-19 2009-01-22 Takeda Pharmaceutical Company Limited Solid preparation comprising alogliptin and metformin hydrochloride
CL2008002427A1 (en) 2007-08-16 2009-09-11 Boehringer Ingelheim Int Pharmaceutical composition comprising 1-chloro-4- (bd-glucopyranos-1-yl) -2- [4 - ((s) -tetrahydrofuran-3-yloxy) benzyl] -benzene combined with 1 - [(4-methylquinazolin- 2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3- (r) -aminopiperidin-1-yl) xanthine; and its use to treat type 2 diabetes mellitus.
US20090082376A1 (en) * 2007-09-26 2009-03-26 Protia, Llc Deuterium-enriched alogliptin
WO2009045476A1 (en) * 2007-10-02 2009-04-09 Concert Pharmaceuticals, Inc. Pyrimidinedione derivatives
PL2214643T3 (en) 2007-11-02 2014-09-30 Acrux Dds Pty Ltd Transdermal delivery system for hormones and steroids
CL2008003653A1 (en) 2008-01-17 2010-03-05 Mitsubishi Tanabe Pharma Corp Use of a glucopyranosyl-derived sglt inhibitor and a selected dppiv inhibitor to treat diabetes; and pharmaceutical composition.
WO2009099171A1 (en) * 2008-02-07 2009-08-13 Takeda Pharmaceutical Company Limited Pharmaceutical product
WO2009099172A1 (en) * 2008-02-07 2009-08-13 Takeda Pharmaceutical Company Limited Pharmaceutical product
PE20091730A1 (en) 2008-04-03 2009-12-10 Boehringer Ingelheim Int FORMULATIONS INVOLVING A DPP4 INHIBITOR
EP2146210A1 (en) 2008-04-07 2010-01-20 Arena Pharmaceuticals, Inc. Methods of using A G protein-coupled receptor to identify peptide YY (PYY) secretagogues and compounds useful in the treatment of conditions modulated by PYY
EP2993239A1 (en) 2008-05-16 2016-03-09 AstraZeneca AB Methods for identifying subjects with an increased likelihood of responding to dpp-iv inhibitors
US20110066940A1 (en) * 2008-05-23 2011-03-17 Nader Asghari Kamrani Music/video messaging system and method
US20170149600A9 (en) * 2008-05-23 2017-05-25 Nader Asghari Kamrani Music/video messaging
BRPI0916997A2 (en) 2008-08-06 2020-12-15 Boehringer Ingelheim International Gmbh DPP-4 INHIBITOR AND ITS USE
UY32030A (en) 2008-08-06 2010-03-26 Boehringer Ingelheim Int "TREATMENT FOR DIABETES IN INAPPROPRIATE PATIENTS FOR THERAPY WITH METFORMIN"
WO2010018217A2 (en) 2008-08-15 2010-02-18 Boehringer Ingelheim International Gmbh Organic compounds for wound healing
US8513264B2 (en) 2008-09-10 2013-08-20 Boehringer Ingelheim International Gmbh Combination therapy for the treatment of diabetes and related conditions
US20200155558A1 (en) 2018-11-20 2020-05-21 Boehringer Ingelheim International Gmbh Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral antidiabetic drug
RU2572529C2 (en) 2008-12-23 2016-01-20 Сандоз Аг Crystalline form of organic compound
CN107011345A (en) 2008-12-23 2017-08-04 勃林格殷格翰国际有限公司 The salt form of organic compound
AR074990A1 (en) 2009-01-07 2011-03-02 Boehringer Ingelheim Int TREATMENT OF DIABETES IN PATIENTS WITH AN INAPPROPRIATE GLUCEMIC CONTROL THROUGH METFORMIN THERAPY
TWI466672B (en) 2009-01-29 2015-01-01 Boehringer Ingelheim Int Treatment for diabetes in paediatric patients
AU2010212867B2 (en) 2009-02-13 2013-05-16 Boehringer Ingelheim International Gmbh Pharmaceutical composition comprising a SGLT2 inhibitor, a DPP-IV inhibitor and optionally a further antidiabetic agent and uses thereof
EA029759B1 (en) 2009-02-13 2018-05-31 Бёрингер Ингельхайм Интернациональ Гмбх Antidiabetic medications comprising dpp-4 inhibitor (linagliptin) optionally in combination with other antidiabetic agents
CN102361557A (en) * 2009-03-26 2012-02-22 Mapi医药公司 Process for the preparation of alogliptin
AR077642A1 (en) 2009-07-09 2011-09-14 Arena Pharm Inc METABOLISM MODULATORS AND THE TREATMENT OF DISORDERS RELATED TO THE SAME
IN2012DN00954A (en) 2009-07-28 2015-04-10 Takeda Pharmaceutical
AU2010294214B2 (en) 2009-09-11 2015-05-07 Vivoryon Therapeutics N.V. Heterocylcic derivatives as inhibitors of glutaminyl cyclase
EP2308847B1 (en) 2009-10-09 2014-04-02 EMC microcollections GmbH Substituted pyridines as inhibitors of dipeptidyl peptidase IV and their application for the treatment of diabetes and related diseases
EP3646859A1 (en) 2009-11-27 2020-05-06 Boehringer Ingelheim International GmbH Treatment of genotyped diabetic patients with dpp-iv inhibitors such as linagliptin
US8648073B2 (en) 2009-12-30 2014-02-11 Fochon Pharma, Inc. Certain dipeptidyl peptidase inhibitors
BR122014017823A2 (en) 2010-01-28 2019-07-16 Avery Dennison Corporation SYSTEM AND METHOD FOR APPLICATION OF LABELS IN ARTICLES
JP6026284B2 (en) 2010-03-03 2016-11-16 プロビオドルグ エージー Inhibitors of glutaminyl cyclase
AU2011226074B2 (en) 2010-03-10 2015-01-22 Vivoryon Therapeutics N.V. Heterocyclic inhibitors of glutaminyl cyclase (QC, EC 2.3.2.5)
US20130109703A1 (en) 2010-03-18 2013-05-02 Boehringer Ingelheim International Gmbh Combination of a GPR119 Agonist and the DPP-IV Inhibitor Linagliptin for Use in the Treatment of Diabetes and Related Conditions
CN102918027A (en) 2010-04-06 2013-02-06 艾尼纳制药公司 Modulators of the gpr119 receptor and the treatment of disorders related thereto
EP2560953B1 (en) 2010-04-21 2016-01-06 Probiodrug AG Inhibitors of glutaminyl cyclase
AU2011249722B2 (en) 2010-05-05 2015-09-17 Boehringer Ingelheim International Gmbh Combination therapy
CN103068392A (en) * 2010-05-12 2013-04-24 Mapi医药公司 Polymorphs of alogliptin benzoate
CN102260265B (en) 2010-05-24 2015-09-02 上海阳帆医药科技有限公司 Hexahydropyrrolo [3,4-b] pyrrole derivative, Its Preparation Method And Use
BR112012032579B1 (en) 2010-06-24 2021-05-11 Boehringer Ingelheim International Gmbh use of linagliptin and pharmaceutical composition comprising linagliptin and long-acting basal insulin
AU2011305525B2 (en) 2010-09-22 2016-08-18 Arena Pharmaceuticals, Inc. Modulators of the GPR119 receptor and the treatment of disorders related thereto
RU2427373C1 (en) 2010-11-08 2011-08-27 Виктор Вениаминович Тец Method for endogenous interferon induction
US9034883B2 (en) 2010-11-15 2015-05-19 Boehringer Ingelheim International Gmbh Vasoprotective and cardioprotective antidiabetic therapy
EP3009136A1 (en) 2011-01-31 2016-04-20 Cadila Healthcare Limited Treatment for lipodystrophy
WO2012118945A2 (en) * 2011-03-03 2012-09-07 Merck Sharp & Dohme Corp. Fused bicyclic heterocycles useful as dipeptidyl peptidase-iv inhibitors
AR085689A1 (en) 2011-03-07 2013-10-23 Boehringer Ingelheim Int PHARMACEUTICAL COMPOSITIONS OF METFORMIN, LINAGLIPTINE AND AN SGLT-2 INHIBITOR
JP6050264B2 (en) 2011-03-16 2016-12-21 プロビオドルグ エージー Benzimidazole derivatives as inhibitors of glutaminyl cyclase
US20140018371A1 (en) 2011-04-01 2014-01-16 Arena Pharmaceuticals, Inc. Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto
US20140066369A1 (en) 2011-04-19 2014-03-06 Arena Pharmaceuticals, Inc. Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto
WO2012145604A1 (en) 2011-04-22 2012-10-26 Arena Pharmaceuticals, Inc. Modulators of the gpr119 receptor and the treatment of disorders related thereto
WO2012145603A1 (en) 2011-04-22 2012-10-26 Arena Pharmaceuticals, Inc. Modulators of the gpr119 receptor and the treatment of disorders related thereto
WO2012170702A1 (en) 2011-06-08 2012-12-13 Arena Pharmaceuticals, Inc. Modulators of the gpr119 receptor and the treatment of disorders related thereto
HUE043540T2 (en) 2011-07-15 2019-08-28 Boehringer Ingelheim Int Substituted dimeric quinazoline derivative, its preparation and its use in pharmaceutical compositions for the treatment of type i and ii diabetes
WO2013046229A1 (en) * 2011-09-26 2013-04-04 Hetero Research Foundation Novel salts of alogliptin
WO2013055910A1 (en) 2011-10-12 2013-04-18 Arena Pharmaceuticals, Inc. Modulators of the gpr119 receptor and the treatment of disorders related thereto
CN103044391B (en) * 2011-10-13 2015-11-25 中国科学院广州生物医药与健康研究院 A kind of DPP-IV inhibitor efficiently
UA108713C2 (en) 2011-11-11 2015-05-25 2-Thiopyrimidinones
US9555001B2 (en) 2012-03-07 2017-01-31 Boehringer Ingelheim International Gmbh Pharmaceutical composition and uses thereof
EP3685839A1 (en) 2012-05-14 2020-07-29 Boehringer Ingelheim International GmbH Linagliptin for use in the treatment of albuminuria and kidney related diseases
WO2013174767A1 (en) 2012-05-24 2013-11-28 Boehringer Ingelheim International Gmbh A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference
CA2874820C (en) 2012-06-05 2020-06-09 Takeda Pharmaceutical Company Limited Disintegrable and preservation stable solid preparation
CN103664801A (en) * 2012-08-30 2014-03-26 重庆医药工业研究院有限责任公司 Method of preparing Alogliptin
CN103788070B (en) * 2012-10-26 2017-10-20 南京华威医药科技开发有限公司 The inhibitor class polymers of DPP 4
WO2014074668A1 (en) 2012-11-08 2014-05-15 Arena Pharmaceuticals, Inc. Modulators of gpr119 and the treatment of disorders related thereto
UA114360C2 (en) 2013-04-22 2017-05-25 Каділа Хелткере Лімітед A novel composition for nonalcoholic fatty liver disease (nafld)
US20160107989A1 (en) 2013-05-30 2016-04-21 Cadila Healthcare Limited A process for preparation of pyrroles having hypolipidemic hypocholesteremic activities
WO2014205234A1 (en) 2013-06-21 2014-12-24 MyoKardia, Inc. Cycloalkyl-substituted pyrimidinedione compounds
JP6603213B2 (en) 2013-06-21 2019-11-06 マイオカーディア，インク Pyrimidinedione compounds for heart conditions
TW201636015A (en) 2013-07-05 2016-10-16 卡地拉保健有限公司 Synergistic compositions
IN2013MU02470A (en) 2013-07-25 2015-06-26 Cadila Healthcare Ltd
US10112898B2 (en) 2013-09-06 2018-10-30 Cadila Healthcare Limited Process for the preparation of saroglitazar pharmaceutical salts
US20160221965A1 (en) 2013-09-16 2016-08-04 Bayer Pharma Aktiengesellschaft Disubstituted trifluoromethyl pyrimidinones and their use
JP6657101B2 (en) 2013-11-05 2020-03-04 ベン グリオン ユニバーシティ オブ ザ ネガフ リサーチ アンド ディベロップメント オーソリティ Compounds for the treatment of diabetes and disease complications resulting therefrom
WO2015092805A1 (en) * 2013-12-18 2015-06-25 Harman Finochem Limited A process for preparation of trelagliptin succinate
WO2015092739A1 (en) * 2013-12-19 2015-06-25 Mylan Laboratories Ltd. Process for preparation of alogliptin
CN104725349A (en) * 2013-12-23 2015-06-24 湖北华世通生物医药科技有限公司 Polycrystalline A-type crystal of alogliptin polycrystalline, preparation method and production purpose thereof
CN104725350A (en) * 2013-12-23 2015-06-24 湖北华世通生物医药科技有限公司 Polycrystalline B-type crystal of alogliptin hydrochloride, preparation method and production purpose thereof
ES2950384T3 (en) 2014-02-28 2023-10-09 Boehringer Ingelheim Int Medical use of a DPP-4 inhibitor
CN105085475B (en) * 2014-05-09 2019-05-21 上海科胜药物研发有限公司 A method of synthesis Egelieting intermediate
CN105315256B (en) * 2014-07-07 2018-02-06 广州朗圣药业有限公司 A kind of preparation method for being adapted to industrialized high-purity amber love song Ge Lieting
CN105384724A (en) * 2014-09-01 2016-03-09 广东东阳光药业有限公司 Fluoro-compound crystalline form and preparation method therefor
CN111440145A (en) * 2014-11-25 2020-07-24 上海医药工业研究院 Novel crystal form of high-purity trelagliptin and preparation method thereof
WO2016113205A1 (en) 2015-01-13 2016-07-21 Bayer Pharma Aktiengesellschaft Substituted pentafluoroethyl pyrimidinones and use thereof
WO2016139677A1 (en) * 2015-03-02 2016-09-09 Msn Laboratories Private Limited Improved process for the preparation of 2-({6-[(3r)-3-aminopiperidin-1-yl]-3-methyl-2,4-dioxo-3,4-dihvdropvrimidin-1(2h)-yl}methyl)benzonitrile and pharmaceutically acceptable salts thereof
CA2979033A1 (en) 2015-03-09 2016-09-15 Intekrin Therapeutics, Inc. Methods for the treatment of nonalcoholic fatty liver disease and/or lipodystrophy
EP3292112B1 (en) 2015-05-04 2019-08-14 Indoco Remedies Limited Process for the preparation of alogliptin
MX2017014128A (en) 2015-05-05 2018-03-15 Pfizer 2-thiopyrimidinones.
EP3310357A1 (en) 2015-06-17 2018-04-25 H e x a l Aktiengesellschaft Alogliptin formulation
WO2017064635A2 (en) 2015-10-14 2017-04-20 Cadila Healthcare Limited Pyrrole compound, compositions and process for preparation thereof
WO2017181924A1 (en) * 2016-04-20 2017-10-26 深圳市塔吉瑞生物医药有限公司 Substituted pyrimidinedione and pharmaceutical composition thereof
CN105837557A (en) * 2016-05-05 2016-08-10 青岛辰达生物科技有限公司 Preparation method of alogliptin for treating type-II diabetes
BR112018072401A2 (en) 2016-06-10 2019-02-19 Boehringer Ingelheim International Gmbh combinations of linagliptin and metformin
CN106039298B (en) * 2016-07-14 2019-11-12 广东天普生化医药股份有限公司 Purposes of the composition containing ulinastatin in preparation treatment prostate cancer drug
CN108072709B (en) * 2016-11-18 2020-11-24 广东东阳光药业有限公司 Method for determining content of enantiomer in trelagliptin succinate bulk drug
US20180243263A1 (en) 2016-12-09 2018-08-30 Cadila Healthcare Ltd. Treatment for primary biliary cholangitis
CN110996951A (en) 2017-04-03 2020-04-10 科赫罗斯生物科学股份有限公司 PPAR gamma agonists for the treatment of progressive supranuclear palsy
PL3461819T3 (en) 2017-09-29 2020-11-30 Probiodrug Ag Inhibitors of glutaminyl cyclase
CN108017614A (en) * 2018-01-25 2018-05-11 中国科学院海洋研究所 DPP-4 inhibitor and its application in treatment diabetes B medicine is prepared
CN108558836A (en) * 2018-05-14 2018-09-21 东南大学 One kind has the DPP-4 inhibitor and application thereof of double action mechanism
CN110950840B (en) * 2019-12-31 2022-03-15 江苏天和制药有限公司 Preparation method of trelagliptin succinate
CN111646941A (en) * 2020-07-17 2020-09-11 天津科技大学 Sulfonamide derivative and preparation method and application thereof
TR202022144A1 (en) 2020-12-29 2022-07-21 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi PHARMACEUTICAL COMPOSITIONS CONTAINING ALOGLIPTINE
TR202022612A2 (en) 2020-12-31 2022-07-21 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi PHARMACEUTICAL CAPSULE COMPOSITIONS OF ALOGLIPTINE
CN115073431B (en) * 2021-04-14 2023-09-05 盐野义制药株式会社 Triazine derivative with virus proliferation inhibition effect and pharmaceutical composition containing triazine derivative

Family Cites Families (323)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB699812A (en) 1950-11-29 1953-11-18 British Ind Solvents Ltd Manufacture of substituted pyrimidones
DE1249281B (en) 1963-05-18
DE1670912C3 (en) 1967-08-18 1981-06-11 Bayer Ag, 5090 Leverkusen Herbicidal agents based on 1,2,4-triazin-5-ones
GB1377642A (en) 1971-01-14 1974-12-18 Koninklijke Gist Spiritus Penicillanic and cephalosporanic acid derivatives
US3960949A (en) 1971-04-02 1976-06-01 Schering Aktiengesellschaft 1,2-Biguanides
DE2142317A1 (en) 1971-08-24 1973-03-01 Bayer Ag Hypnotic uracil derivs - which do not have narcotic props
DE2150686A1 (en) * 1971-10-12 1973-04-19 Basf Ag 6-amino-uracil-5-carboxylic acid thioamides - inters for dyestuffs and pharmaceuticals
US3838128A (en) * 1971-11-22 1974-09-24 American Cyanamid Co Process for the preparation of certain n-3-substituted-6-(trichloromethyl)uracils
BE792206A (en) 1971-12-02 1973-06-01 Byk Gulden Lomberg Chem Fab
AU5996573A (en) 1972-09-11 1975-03-06 Commonwealth Scientific And Industrial Research Organisation Pyridinium salts
US3823135A (en) 1972-12-26 1974-07-09 Shell Oil Co Pyrimidone herbicides
GB1464248A (en) 1973-11-01 1977-02-09 Ici Ltd Substituted triazinediones their preparation and use as herbicides
DE2361551A1 (en) 1973-12-11 1975-06-19 Basf Ag Watersol. azo dyes derived from substd. pyridinium chlorides - dyeing natural and synthetic polyamides yellow-violet shades
DE2500024A1 (en) 1975-01-02 1976-07-08 Basf Ag Soluble azo dyes for dying polyamides - prepd. by coupling of 4,6-diaminopyridone derivs
JPS535180A (en) 1976-07-01 1978-01-18 Sumitomo Chem Co Ltd Preparation of 3,4-dihydro-2 (1h) quinazoline derivatives
DE2720085A1 (en) 1977-05-05 1978-11-16 Hoechst Ag PYRIMIDO (6.1-A) ISOCHINOLIN-2-ON DERIVATIVES
US4494978A (en) 1976-12-30 1985-01-22 Chevron Research Company Herbicidal N-(N'-hydrocarbyloxycarbamylalkyl)-2,6-dialkyl-alpha-haloacetanilides
DE3011809A1 (en) * 1980-03-27 1981-10-01 Cassella Ag, 6000 Frankfurt PYRIMIDYL-CHINAZOLINE, METHOD FOR THE PRODUCTION THEREOF, PHARMACEUTICAL PREPARATIONS CONTAINING IT AND THEIR USE
CH657851A5 (en) 1983-06-28 1986-09-30 Ciba Geigy Ag CHROMOGENEOUS CHINAZOLONE COMPOUNDS.
AR240698A1 (en) 1985-01-19 1990-09-28 Takeda Chemical Industries Ltd Process for the preparation of 5-(4-(2-(5-ethyl-2-pyridil)-ethoxy)benzyl)-2,4-thiazolodinedione and their salts
EP0237289A3 (en) 1986-03-14 1988-07-27 Takeda Chemical Industries, Ltd. Pyrazolo [3,4-d] pyrimidine derivatives, their production and use
US5614492A (en) 1986-05-05 1997-03-25 The General Hospital Corporation Insulinotropic hormone GLP-1 (7-36) and uses thereof
EP0842925A1 (en) 1987-09-04 1998-05-20 Beecham Group Plc Substituted thiazolidinedione derivatives
US4935493A (en) 1987-10-06 1990-06-19 E. I. Du Pont De Nemours And Company Protease inhibitors
JPH01143895A (en) * 1987-11-30 1989-06-06 Meiji Seika Kaisha Ltd Pyrimidine derivative
FR2631625B1 (en) * 1988-05-17 1992-10-16 Synthelabo PHENYL-6 DERIVATIVES PIPERAZINYLALKYL-3 1H, 3H-PYRIMIDINEDIONE-2,4, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION
GB8900382D0 (en) 1989-01-09 1989-03-08 Janssen Pharmaceutica Nv 2-aminopyrimidinone derivatives
US5433955A (en) 1989-01-23 1995-07-18 Akzo N.V. Site specific in vivo activation of therapeutic drugs
IE63502B1 (en) 1989-04-21 1995-05-03 Zeneca Ltd Aminopyrimidine derivatives useful for treating cardiovascular disorders
USRE37979E1 (en) * 1989-09-29 2003-02-04 Mitsubishi Chemical Corporation Pyrimidine derivatives and anti-viral agent containing the same as active ingredient thereof
US5366862A (en) 1990-02-14 1994-11-22 Receptor Laboratories, Inc. Method for generating and screening useful peptides
US5814460A (en) 1990-02-14 1998-09-29 Diatide, Inc. Method for generating and screening useful peptides
US5162326A (en) * 1990-02-15 1992-11-10 Takeda Chemical Industries, Ltd. Pyrimidinedione derivatives, their production and use
JP3032844B2 (en) * 1990-02-15 2000-04-17 武田薬品工業株式会社 Pyrimidinedione derivative
US5462928A (en) 1990-04-14 1995-10-31 New England Medical Center Hospitals, Inc. Inhibitors of dipeptidyl-aminopeptidase type IV
DE4110019C2 (en) 1991-03-27 2000-04-13 Merck Patent Gmbh Imidazopyridines, processes for their production and pharmaceutical preparations containing them
US5387512A (en) 1991-06-07 1995-02-07 Merck & Co. Inc. Preparation of 3-[z-benzoxazol-2-yl)ethyl]-5-(1-hydroxyethyl)-6-methyl-2-(1H)-pyridinone by biotransformation
DK0610317T3 (en) 1991-10-22 2001-02-19 New England Medical Center Inc Inhibitors of dipeptidyl aminopeptidase type IV
US6825169B1 (en) 1991-10-22 2004-11-30 Trustees Of Tufts College Inhibitors of dipeptidyl-aminopeptidase type IV
US5350752A (en) 1991-12-16 1994-09-27 E. R. Squibb & Sons, Inc. Dihydropyrimidine derivatives
DE4141788A1 (en) 1991-12-18 1993-06-24 Merck Patent Gmbh imidazopyridines
DE4208050A1 (en) * 1992-03-13 1993-09-23 Bayer Ag AZOLYL METHYL FLUORCYCLOPROPYL DERIVATIVES
DE4305602A1 (en) 1992-06-17 1993-12-23 Merck Patent Gmbh imidazopyridines
ZA936492B (en) 1992-09-10 1995-03-02 Lilly Co Eli Compounds useful as hypoglycemic agents and for treating Alzheimer's disease.
IL106998A0 (en) 1992-09-17 1993-12-28 Univ Florida Brain-enhanced delivery of neuroactive peptides by sequential metabolism
JP3481984B2 (en) * 1992-12-29 2003-12-22 武田薬品工業株式会社 Pyridopyrimidine derivatives, their production and use
US5811281A (en) 1993-07-12 1998-09-22 Cornell Research Foundation, Inc. Immortalized intestinal epithelial cell lines
US5391541A (en) * 1993-08-11 1995-02-21 Fmc Corporation Herbicidal 3-(substituted-benzyl)-1-methyl-6-trifluoromethyluracils
US5683966A (en) * 1993-08-11 1997-11-04 Fmc Corporation Herbicidal 3-(substituted-benzyl)-1-methyl-6-trifluoromethyluracils
IL111785A0 (en) 1993-12-03 1995-01-24 Ferring Bv Dp-iv inhibitors and pharmaceutical compositions containing them
DE4341453A1 (en) 1993-12-06 1995-06-08 Merck Patent Gmbh imidazopyridines
KR100233703B1 (en) 1994-03-08 1999-12-01 오츠까 요시미쯔 Phosphonic diester derivative
US5580979A (en) 1994-03-15 1996-12-03 Trustees Of Tufts University Phosphotyrosine peptidomimetics for inhibiting SH2 domain interactions
US5543396A (en) 1994-04-28 1996-08-06 Georgia Tech Research Corp. Proline phosphonate derivatives
AU2790895A (en) 1994-06-10 1996-01-05 Universitaire Instelling Antwerpen Purification of serine protease and synthetic inhibitors thereof
US5601986A (en) 1994-07-14 1997-02-11 Amgen Inc. Assays and devices for the detection of extrahepatic biliary atresia
DE4432860A1 (en) 1994-09-15 1996-03-21 Merck Patent Gmbh imidazopyridines
US5512549A (en) 1994-10-18 1996-04-30 Eli Lilly And Company Glucagon-like insulinotropic peptide analogs, compositions, and methods of use
US5614379A (en) 1995-04-26 1997-03-25 Eli Lilly And Company Process for preparing anti-obesity protein
JP2002515724A (en) 1995-06-01 2002-05-28 ダナ−ファーバー キャンサー インスティテュート インコーポレイテッド Novel form of dipeptidyl peptidase IV (CD26) found in human serum, antibodies and uses thereof
US6325989B1 (en) 1995-06-01 2001-12-04 Dana-Farber Cancer Institute, Inc. Form of dipeptidylpeptidase IV (CD26) found in human serum
EP0748800B1 (en) 1995-06-09 2001-05-09 F. Hoffmann-La Roche Ag Pyrimidinedione, pyrimidinetrione, triazinedione derivatives as alpha-1-adrenergic receptor antagonists
JPH0928376A (en) 1995-07-21 1997-02-04 Ajinomoto Co Inc New dipeptidyl peptidase iv and its production
EP1327659B1 (en) 1995-10-13 2005-06-08 Crompton Vinyl Additives GmbH Stabiliser combinations for chlorinated polymers
DE122010000020I1 (en) 1996-04-25 2010-07-08 Prosidion Ltd Method for lowering the blood glucose level in mammals
US20020006899A1 (en) 1998-10-06 2002-01-17 Pospisilik Andrew J. Use of dipeptidyl peptidase IV effectors for lowering blood pressure in mammals
US5965532A (en) 1996-06-28 1999-10-12 Trustees Of Tufts College Multivalent compounds for crosslinking receptors and uses thereof
US5885997A (en) 1996-07-01 1999-03-23 Dr. Reddy's Research Foundation Heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases
CZ298812B6 (en) 1996-07-01 2008-02-13 Dr. Reddy's Laboratories Limited Azolidinedione derivatives, process of their preparation, pharmaceutical compositions in which the derivatives are comprised and their use in the treatment of diabetes mellitus and related diseases
US7235627B2 (en) 1996-08-30 2007-06-26 Novo Nordisk A/S Derivatives of GLP-1 analogs
US6006753A (en) 1996-08-30 1999-12-28 Eli Lilly And Company Use of GLP-1 or analogs to abolish catabolic changes after surgery
US6458924B2 (en) 1996-08-30 2002-10-01 Novo Nordisk A/S Derivatives of GLP-1 analogs
US6011155A (en) 1996-11-07 2000-01-04 Novartis Ag N-(substituted glycyl)-2-cyanopyrrolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV
GB9702701D0 (en) 1997-02-01 1997-04-02 Univ Newcastle Ventures Ltd Quinazolinone compounds
US20030060434A1 (en) 1997-02-18 2003-03-27 Loretta Nielsen Combined tumor suppressor gene therapy and chemotherapy in the treatment of neoplasms
US6100234A (en) 1997-05-07 2000-08-08 Tufts University Treatment of HIV
DE69840230D1 (en) 1997-05-16 2009-01-02 Novozymes Inc POLYPEPTIDES WITH PROLYLDIPEPTIDYLAMINOPEPTIDASE ACTIVITY AND NUCLEIC ACIDS THAT CODE FOR IT
US6011786A (en) * 1997-06-06 2000-01-04 Ericsson Inc. Systems and methods for control channel communication in cellular radiotelephone systems
EP0897012A1 (en) 1997-07-05 1999-02-17 Societe Des Produits Nestle S.A. Cloning of the prolyl-dipeptidyl-peptidase from aspergillus oryzae
US6235493B1 (en) 1997-08-06 2001-05-22 The Regents Of The University Of California Amino acid substituted-cresyl violet, synthetic fluorogenic substrates for the analysis of agents in individual in vivo cells or tissue
ES2285785T3 (en) 1997-09-29 2007-11-16 Point Therapeutics, Inc. STIMULATION OF IN VITRO HEMATOPOYETIC CELLS.
US6485955B1 (en) 1997-10-06 2002-11-26 The Trustees Of Tufts University Quiescent cell dipeptidyl peptidase: a novel cytoplasmic serine protease
US6342611B1 (en) 1997-10-10 2002-01-29 Cytovia, Inc. Fluorogenic or fluorescent reporter molecules and their applications for whole-cell fluorescence screening assays for capsases and other enzymes and the use thereof
WO1999025719A1 (en) 1997-11-18 1999-05-27 Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai Novel physiologically active substance sulphostin, process for producing the same, and use thereof
FR2771004B1 (en) * 1997-11-19 2000-02-18 Inst Curie USE OF BENZHYDRYL SULFINYL DERIVATIVES FOR THE MANUFACTURE OF MEDICINAL PRODUCTS HAVING A WAKING EFFECT IN SITUATIONS OF DRUG-BASED VIGILANCE DISORDERS
EP1042457B1 (en) 1997-12-16 2006-03-08 Novozymes A/S Polypeptides having aminopeptidase activity and nucleic acids encoding same
US6380357B2 (en) 1997-12-16 2002-04-30 Eli Lilly And Company Glucagon-like peptide-1 crystals
AU766219B2 (en) 1998-02-02 2003-10-09 1149336 Ontario Inc. Method of regulating glucose metabolism, and reagents related thereto
US20020061839A1 (en) 1998-03-09 2002-05-23 Scharpe Simon Lodewijk Serine peptidase modulators
FR2777283B1 (en) 1998-04-10 2000-11-24 Adir NOVEL GLUCAGON-PEPTIDE- 1 (7-37) ANALOGUE PEPTIDE COMPOUNDS, PROCESS FOR THEIR PREPARATION AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME
DE19816857A1 (en) * 1998-04-16 1999-10-21 Boehringer Ingelheim Pharma Novel adenosine antagonists useful in treatment of e.g. neurodegenerative, pulmonary, renal and cardiovascular disorders
DE19823831A1 (en) 1998-05-28 1999-12-02 Probiodrug Ges Fuer Arzneim New pharmaceutical use of isoleucyl thiazolidide and its salts
ES2189423T3 (en) 1998-06-05 2003-07-01 Point Therapeutics Inc BOROPROLINE CYCLING COMPOUNDS.
DE19828114A1 (en) 1998-06-24 2000-01-27 Probiodrug Ges Fuer Arzneim Produgs of unstable inhibitors of dipeptidyl peptidase IV
DE19828113A1 (en) 1998-06-24 2000-01-05 Probiodrug Ges Fuer Arzneim Prodrugs of Dipeptidyl Peptidase IV Inhibitors
EP0967208B1 (en) 1998-06-26 2002-08-14 Crompton Vinyl Additives GmbH In 5-position substituted 6-aminouracils as stabilisers for halogen-containing polymers
EP0967209B1 (en) 1998-06-26 2003-01-08 Crompton Vinyl Additives GmbH NH2-modified 6-aminouracils as stabilisers for halogen-containing polymers
EP0967245A1 (en) 1998-06-26 1999-12-29 Witco Vinyl Additives GmbH 1,3 substituted 6-aminouraciles to stabilize halogenated polymers
US6129911A (en) 1998-07-10 2000-10-10 Rhode Island Hospital, A Lifespan Partner Liver stem cell
DE19834591A1 (en) 1998-07-31 2000-02-03 Probiodrug Ges Fuer Arzneim Use of substances that decrease the activity of dipeptidyl peptidase IV to increase blood sugar levels, e.g. for treating hypoglycemia
US6177437B1 (en) * 1998-09-04 2001-01-23 University Of Massachusetts Medical Center Inhibitors of Herpes Simplex virus uracil-DNA glycosylase
US20030176357A1 (en) 1998-10-06 2003-09-18 Pospisilik Andrew J. Dipeptidyl peptidase IV inhibitors and their uses for lowering blood pressure levels
CO5150173A1 (en) 1998-12-10 2002-04-29 Novartis Ag COMPOUNDS N- (REPLACED GLYCLE) -2-DIPEPTIDYL-IV PEPTIDASE INHIBITING CYANOPIRROLIDINS (DPP-IV) WHICH ARE EFFECTIVE IN THE TREATMENT OF CONDITIONS MEDIATED BY DPP-IV INHIBITION
GB9906715D0 (en) 1999-03-23 1999-05-19 Ferring Bv Compositions for promoting growth
US6548529B1 (en) 1999-04-05 2003-04-15 Bristol-Myers Squibb Company Heterocyclic containing biphenyl aP2 inhibitors and method
DE19915388A1 (en) * 1999-04-06 2000-10-12 Witco Vinyl Additives Gmbh 4-aminopyrimidinones and oxazolidino-4-aminopyrimidinones, processes for their preparation and their use for stabilizing halogen-containing polymers
KR20000065885A (en) * 1999-04-10 2000-11-15 최승주 Antiviral pyrimidinedione derivatives and process for the preparation thereof
AU3958100A (en) 1999-04-20 2000-11-02 Novo Nordisk A/S New compounds, their preparation and use
ATE252601T1 (en) 1999-05-17 2003-11-15 Conjuchem Inc LONG-ACTING INSULINOTROPE PEPTIDES
DE19926233C1 (en) 1999-06-10 2000-10-19 Probiodrug Ges Fuer Arzneim Production of thiazolidine, useful as pharmaceutical intermediate, comprises reacting hexamethylenetetramine with cysteamine
US6172081B1 (en) 1999-06-24 2001-01-09 Novartis Ag Tetrahydroisoquinoline 3-carboxamide derivatives
US6110949A (en) 1999-06-24 2000-08-29 Novartis Ag N-(substituted glycyl)-4-cyanothiazolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV
US6107317A (en) 1999-06-24 2000-08-22 Novartis Ag N-(substituted glycyl)-thiazolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV
US6528486B1 (en) 1999-07-12 2003-03-04 Zealand Pharma A/S Peptide agonists of GLP-1 activity
US6617340B1 (en) 1999-07-29 2003-09-09 Novartis Ag N-(substituted glycyl)-pyrrolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV
DE19940130A1 (en) 1999-08-24 2001-03-01 Probiodrug Ges Fuer Arzneim New effectors of Dipeptidyl Peptidase IV for topical use
US6340705B1 (en) * 1999-09-10 2002-01-22 Monsanto Technology, Llc Use of α-linolenic acid metabolites for treatment or prevention of cancer
US6559188B1 (en) 1999-09-17 2003-05-06 Novartis Ag Method of treating metabolic disorders especially diabetes, or a disease or condition associated with diabetes
US6414002B1 (en) 1999-09-22 2002-07-02 Bristol-Myers Squibb Company Substituted acid derivatives useful as antidiabetic and antiobesity agents and method
WO2001023364A1 (en) 1999-09-28 2001-04-05 Merck Patent Gmbh Quinazolinones
US6447772B1 (en) 1999-10-01 2002-09-10 Klaire Laboratories, Inc. Compositions and methods relating to reduction of symptoms of autism
US6251391B1 (en) 1999-10-01 2001-06-26 Klaire Laboratories, Inc. Compositions containing dipepitidyl peptidase IV and tyrosinase or phenylalaninase for reducing opioid-related symptons
CA2392209A1 (en) 1999-10-08 2001-04-19 Kazuyuki Fujishima M-substituted benzoic acid derivatives having integrin .alpha.v.beta.3 antagonistic activity
US6261794B1 (en) 1999-10-14 2001-07-17 Saint Louis University Methods for identifying inhibitors of methionine aminopeptidases
US7230000B1 (en) 1999-10-27 2007-06-12 Cytokinetics, Incorporated Methods and compositions utilizing quinazolinones
WO2001034594A1 (en) 1999-11-12 2001-05-17 Guilford Pharmaceuticals, Inc. Dipeptidyl peptidase iv inhibitors and methods of making and using dipeptidyl peptidase iv inhibitors
US20040152745A1 (en) 1999-11-12 2004-08-05 Guilford Pharmaceuticals, Inc. Dipeptidyl peptidase IV inhibitors and methods of making and using dipeptidyl peptidase IV inhibitors
GB9928330D0 (en) 1999-11-30 2000-01-26 Ferring Bv Novel antidiabetic agents
AU2020501A (en) 1999-12-08 2001-06-18 1149336 Ontario Inc. Chemotherapy treatment
US6380398B2 (en) 2000-01-04 2002-04-30 Novo Nordisk A/S Therapeutically active and selective heterocyclic compounds that are inhibitors of the enzyme DPP-IV
ES2436610T3 (en) 2000-01-21 2014-01-03 Novartis Ag Combinations containing dipeptidylpeptidase-IV inhibitors and antidiabetic agents
PT1255738E (en) * 2000-01-25 2012-06-19 Neurocrine Biosciences Inc Gonadotropin-releasing hormone receptor antagonists and methods relating thereto
US7598222B2 (en) 2000-01-27 2009-10-06 Eli Lilly And Company Process for solubilizing glucagon-like peptide 1 compounds
US6569901B2 (en) 2000-01-28 2003-05-27 Novo Nordisk A/S Alkynyl-substituted propionic acid derivatives, their preparation and use
US7217722B2 (en) 2000-02-01 2007-05-15 Kirin Beer Kabushiki Kaisha Nitrogen-containing compounds having kinase inhibitory activity and drugs containing the same
JP4088011B2 (en) * 2000-02-16 2008-05-21 株式会社東芝 Semiconductor device and manufacturing method thereof
US6448045B1 (en) 2000-03-10 2002-09-10 The Regents Of The University Of California Inducing insulin gene expression in pancreas cells expressing recombinant PDX-1
US6395767B2 (en) 2000-03-10 2002-05-28 Bristol-Myers Squibb Company Cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV and method
US6608038B2 (en) 2000-03-15 2003-08-19 Novartis Ag Methods and compositions for treatment of diabetes and related conditions via gene therapy
EP1136482A1 (en) 2000-03-23 2001-09-26 Sanofi-Synthelabo 2-Amino-3-(alkyl)-pyrimidone derivatives as GSK3beta inhibitors
US6555519B2 (en) 2000-03-30 2003-04-29 Bristol-Myers Squibb Company O-glucosylated benzamide SGLT2 inhibitors and method
DK2055302T3 (en) 2000-03-31 2014-10-27 Royalty Pharma Collection Trust PROCEDURE FOR IMPROVING ISLAND CELL SIGNALS BY DIABETES MELLITUS AND PREVENTION thereof
US6573096B1 (en) 2000-04-01 2003-06-03 The Research Foundation At State University Of New York Compositions and methods for inhibition of cancer invasion and angiogenesis
US6545170B2 (en) 2000-04-13 2003-04-08 Pharmacia Corporation 2-amino-5, 6 heptenoic acid derivatives useful as nitric oxide synthase inhibitors
SI2223922T1 (en) 2000-04-25 2016-04-29 Icos Corporation Inhibitors of human phosphatidyl-inositol 3-kinase delta
GB0010183D0 (en) 2000-04-26 2000-06-14 Ferring Bv Inhibitors of dipeptidyl peptidase IV
GB0010188D0 (en) 2000-04-26 2000-06-14 Ferring Bv Inhibitors of dipeptidyl peptidase IV
US6783757B2 (en) 2000-06-01 2004-08-31 Kirkman Group, Inc. Composition and method for increasing exorphin catabolism to treat autism
TW583185B (en) 2000-06-13 2004-04-11 Novartis Ag N-(substituted glycyl)-2-cyanopyrrolidines and pharmaceutical composition for inhibiting dipeptidyl peptidase-IV (DPP-IV) or for the prevention or treatment of diseases or conditions associated with elevated levels of DPP-IV comprising the same
US6432969B1 (en) 2000-06-13 2002-08-13 Novartis Ag N-(substituted glycyl)-2 cyanopyrrolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV
US6627636B2 (en) 2000-06-15 2003-09-30 Bristol-Myers Squibb Company HMG-CoA reductase inhibitors and method
US6620821B2 (en) 2000-06-15 2003-09-16 Bristol-Myers Squibb Company HMG-CoA reductase inhibitors and method
US7078397B2 (en) 2000-06-19 2006-07-18 Smithkline Beecham Corporation Combinations of dipeptidyl peptidase IV inhibitors and other antidiabetic agents for the treatment of diabetes mellitus
GB0014969D0 (en) 2000-06-19 2000-08-09 Smithkline Beecham Plc Novel method of treatment
US6558188B1 (en) * 2000-06-22 2003-05-06 Hewlett Packard Development Company, L.P. Impedance controlled electrical connector assembly
EP1561752A1 (en) * 2000-07-04 2005-08-10 Novo Nordisk A/S Heterocyclic compounds that are inhibitors of the enzyme DPP-IV
MXPA02012272A (en) * 2000-07-04 2003-04-25 Novo Nordisk As Heterocyclic compounds, which are inhibitors of the enzyme dpp-iv.
JP2002042960A (en) 2000-07-25 2002-02-08 Yazaki Corp Connector support mechanism
US6495544B2 (en) 2000-08-01 2002-12-17 Pharmacia Corporation Homoiminopiperidinyl hexanoic acid inhibitors of inducible nitric oxide synthase
CA2417942C (en) 2000-08-04 2010-06-29 Warner-Lambert Company 2-(4-pyridyl)amino-6-dialkoxyphenyl-pyrido[2,3-d]pyrimidin-7-ones
EP1950199B1 (en) 2000-08-10 2009-12-02 Mitsubishi Tanabe Pharma Corporation Proline derivatives and use thereof as drugs
US20020165237A1 (en) 2000-08-11 2002-11-07 Fryburg David Albert Treatment of the insulin resistance syndrome
US20020037829A1 (en) 2000-08-23 2002-03-28 Aronson Peter S. Use of DPPIV inhibitors as diuretic and anti-hypertensive agents
US6900226B2 (en) 2000-09-06 2005-05-31 Hoffman-La Roche Inc. Neuropeptide Y antagonists
CA2423141A1 (en) 2000-09-27 2002-04-04 Merck & Co., Inc. Benzopyrancarboxylic acid derivatives for the treatment of diabetes and lipid disorders
US20020064736A1 (en) 2000-09-27 2002-05-30 Fuji Photo Film Co., Ltd. Dye-forming coupler, silver halide photographic light-sensitive material, and method for producing an azomethine dye
KR100526091B1 (en) 2000-10-06 2005-11-08 다나베 세이야꾸 가부시키가이샤 Aliphatic Nitrogenous Five-Membered Ring Compounds
CA2425001A1 (en) 2000-10-12 2002-04-18 Ferring Bv Novel serine protease genes related to dppiv
CN101143217A (en) 2000-10-27 2008-03-19 前体生物药物股份有限公司 Treatment of neurological and neuropsychological disorders
AUPR107800A0 (en) 2000-10-27 2000-11-23 University Of Sydney, The Peptide and nucleic acid molecule ii
BR0115055A (en) 2000-10-30 2003-12-30 Ortho Mcneil Pharm Inc Combination therapy comprising anticonvulsant and antidiabetic agents
WO2002060434A2 (en) 2000-10-31 2002-08-08 Merck & Co., Inc. Benzopyrancarboxylic acid derivatives for the treatment of diabetes and lipid disorders
WO2002059343A2 (en) 2000-10-31 2002-08-01 Vanderbilt University Biological markers and diagnostic tests for angiotensin converting enzyme inhibitor- and vasopeptidase inhibitor-associated angioedema
AU2002225954A1 (en) 2000-11-08 2002-05-21 The University Of Georgia Research Foundation, Inc. Dipeptidylpeptidases and methods of use
US20030055052A1 (en) 2000-11-10 2003-03-20 Stefan Peters FAP-activated anti-tumor compounds
US20020155565A1 (en) 2000-11-10 2002-10-24 Pilar Garin-Chesa FAP-activated anti-tumor compounds
TWI243162B (en) 2000-11-10 2005-11-11 Taisho Pharmaceutical Co Ltd Cyanopyrrolidine derivatives
US20030203946A1 (en) 2000-11-17 2003-10-30 Carsten Behrens Glucagon antagonists/inverse agonists
CA2436854A1 (en) 2000-11-20 2002-05-23 Bristol-Myers Squibb Company Pyridone derivatives as ap2 inhibitors
EP1343505A1 (en) 2000-12-11 2003-09-17 Tularik Inc. Cxcr3 antagonists
JPWO2002051836A1 (en) 2000-12-27 2004-04-22 協和醗酵工業株式会社 Dipeptidyl peptidase-IV inhibitor
DE10100053A1 (en) 2001-01-02 2002-08-22 Keyneurotek Ag I G Use of enzyme inhibitors of dipeptidyl peptidase IV and aminopeptidase N and pharmaceutical preparations therefrom for the prevention and / or therapy of ischemia-related acute and chronic neurodegenerative processes and diseases
PL364221A1 (en) 2001-02-02 2004-12-13 Takeda Chemical Industries, Ltd. Fused heterocyclic compounds
TWI255817B (en) 2001-02-14 2006-06-01 Kissei Pharmaceutical Glucopyranosyloxybenzylbenzene derivatives and medicinal use thereof
PT1368349E (en) 2001-02-24 2007-04-30 Boehringer Ingelheim Pharma Xanthine derivative, production and use thereof as a medicament
US6337069B1 (en) 2001-02-28 2002-01-08 B.M.R.A. Corporation B.V. Method of treating rhinitis or sinusitis by intranasally administering a peptidase
JP4178816B2 (en) 2001-03-15 2008-11-12 田辺三菱製薬株式会社 Pharmaceutical composition
WO2002074042A2 (en) 2001-03-19 2002-09-26 Novartis Ag Combinations comprising an antidiarrheal agent and an epothilone or an epothilone derivative
ATE395912T1 (en) 2001-03-27 2008-06-15 Merck & Co Inc DIPEPTIDYLPEPTIDASE INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
FR2822826B1 (en) 2001-03-28 2003-05-09 Servier Lab NOVEL ALPHA-AMINO ACID SULPHONYL DERIVATIVES, PROCESS FOR PREPARING THEM AND PHARMACEUTICAL COMPOSITIONS CONTAINING SAME
DE10115921A1 (en) 2001-03-30 2002-10-02 Boehringer Ingelheim Pharma Process for the preparation of 4,6-diaminopyrimido [5,4-d] pyrimidines
US6890905B2 (en) 2001-04-02 2005-05-10 Prosidion Limited Methods for improving islet signaling in diabetes mellitus and for its prevention
GB0109146D0 (en) 2001-04-11 2001-05-30 Ferring Bv Treatment of type 2 diabetes
PE20021080A1 (en) 2001-04-12 2003-02-12 Boehringer Ingelheim Int A SPECIFIC ANTIBODY FAPO BIBH1 IN THE TREATMENT OF CANCER
US6573287B2 (en) 2001-04-12 2003-06-03 Bristo-Myers Squibb Company 2,1-oxazoline and 1,2-pyrazoline-based inhibitors of dipeptidyl peptidase IV and method
US7462012B2 (en) 2001-05-14 2008-12-09 F.R. Drake Company Stack transfer device
FR2824825B1 (en) 2001-05-15 2005-05-06 Servier Lab NOVEL ALPHA-AMINOACID DERIVATIVES, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
US20030060494A1 (en) 2001-05-18 2003-03-27 Nobuyuki Yasuda Pharmaceutical use of N-carbamoylazole derivatives
US7105556B2 (en) 2001-05-30 2006-09-12 Bristol-Myers Squibb Company Conformationally constrained analogs useful as antidiabetic and antiobesity agents and method
US6794379B2 (en) 2001-06-06 2004-09-21 Tularik Inc. CXCR3 antagonists
JP2005500308A (en) 2001-06-20 2005-01-06 メルク　エンド　カムパニー　インコーポレーテッド Dipeptidyl peptidase inhibitors for the treatment of diabetes
CA2450579A1 (en) 2001-06-20 2003-01-03 Merck & Co., Inc. Dipeptidyl peptidase inhibitors for the treatment of diabetes
IL158923A0 (en) 2001-06-27 2004-05-12 Smithkline Beecham Corp Fluoropyrrolidines as dipeptidyl peptidase inhibitors
JP4300108B2 (en) 2001-06-27 2009-07-22 スミスクライン ビーチャム コーポレーション Pyrrolidines as dipeptidyl peptidase inhibitors
DE10150203A1 (en) 2001-10-12 2003-04-17 Probiodrug Ag Use of dipeptidyl peptidase IV inhibitor in treatment of cancer
US20030135023A1 (en) 2001-06-27 2003-07-17 Hans-Ulrich Demuth Peptide structures useful for competitive modulation of dipeptidyl peptidase IV catalysis
DE10154689A1 (en) 2001-11-09 2003-05-22 Probiodrug Ag Substituted amino ketone compounds
US7368421B2 (en) 2001-06-27 2008-05-06 Probiodrug Ag Use of dipeptidyl peptidase IV inhibitors in the treatment of multiple sclerosis
WO2003002595A2 (en) 2001-06-27 2003-01-09 Probiodrug Ag Dipeptidyl peptidase iv inhibitors and their uses as anti-cancer agents
US20030130199A1 (en) 2001-06-27 2003-07-10 Von Hoersten Stephan Dipeptidyl peptidase IV inhibitors and their uses as anti-cancer agents
CA2419888A1 (en) 2001-06-27 2003-01-09 Probiodrug Ag Peptide structures useful for competitive modulation of dipeptidyl peptidase iv catalysis
ATE370943T1 (en) 2001-06-27 2007-09-15 Smithkline Beecham Corp FLUOROPYRROLIDINE AS DIPEPTIDYL-PEPTIDASE INHIBITORS
US6869947B2 (en) 2001-07-03 2005-03-22 Novo Nordisk A/S Heterocyclic compounds that are inhibitors of the enzyme DPP-IV
UA74912C2 (en) 2001-07-06 2006-02-15 Merck & Co Inc Beta-aminotetrahydroimidazo-(1,2-a)-pyrazines and tetratriazolo-(4,3-a)-pyrazines as inhibitors of dipeptylpeptidase for the treatment or prevention of diabetes
AU2002322585A1 (en) 2001-07-20 2003-03-03 Adipogenix, Inc. Fat accumulation-modulating compounds
TW524754B (en) 2001-07-24 2003-03-21 Nano Dynamics Inc Ink supplying cassette having under pressure regulation mechanism
EP1285922A1 (en) 2001-08-13 2003-02-26 Warner-Lambert Company 1-Alkyl or 1-cycloalkyltriazolo[4,3-a]quinazolin-5-ones as phosphodiesterase inhibitors
JP2005508891A (en) 2001-08-13 2005-04-07 プロバイオドラッグ アーゲー Regumain irreversible cysteine protease inhibitor
JP2003128551A (en) 2001-08-15 2003-05-08 Sankyo Co Ltd New antidiabetic pharmaceutical composition
DE10143840A1 (en) 2001-09-06 2003-03-27 Probiodrug Ag New acylated hydroxamates useful for the treatment of e.g. wound healing
US6844316B2 (en) 2001-09-06 2005-01-18 Probiodrug Ag Inhibitors of dipeptidyl peptidase I
US20030186963A1 (en) 2001-09-14 2003-10-02 Dorwald Florencio Zaragoza Substituted piperidines
US6673829B2 (en) 2001-09-14 2004-01-06 Novo Nordisk A/S Aminoazetidine,-pyrrolidine and -piperidine derivatives
TWI246510B (en) 2001-09-14 2006-01-01 Mitsubishi Pharma Corp Thiazolidine derivatives and pharmaceutical uses thereof
WO2003024965A2 (en) 2001-09-19 2003-03-27 Novo Nordisk A/S Heterocyclic compounds that are inhibitors of the enzyme dpp-iv
PL204653B1 (en) 2001-09-21 2010-01-29 Bristol Myers Squibb Co Derivative of pyrazolo [3,4-c] pyridine, the use thereof and pharmaceutical composition
PL368816A1 (en) 2001-09-21 2005-04-04 Mitsubishi Pharma Corporation 3-substituted-4-pyrimidone derivatives
TWI265164B (en) 2001-09-21 2006-11-01 Mitsubishi Pharma Corp 3-substituted-4-pyrimidone derivatives
US7019010B2 (en) 2001-09-27 2006-03-28 Novertis Ag Combinations
CN1596253A (en) 2001-10-01 2005-03-16 布里斯托尔-迈尔斯斯奎布公司 Spiro-hydantoin compounds useful as anti-inflammatory agents
WO2003030946A1 (en) 2001-10-09 2003-04-17 Novartis Ag Regulation of insulin production
US7064135B2 (en) 2001-10-12 2006-06-20 Novo Nordisk Inc. Substituted piperidines
TWI301834B (en) 2001-10-22 2008-10-11 Eisai R&D Man Co Ltd Pyrimidone compound and pharmaceutical composition including the same
GB0125445D0 (en) * 2001-10-23 2001-12-12 Ferring Bv Protease Inhibitors
US6861440B2 (en) 2001-10-26 2005-03-01 Hoffmann-La Roche Inc. DPP IV inhibitors
EP1442028A4 (en) 2001-11-06 2009-11-04 Bristol Myers Squibb Co Substituted acid derivatives useful as antidiabetic and antiobesity agents and method
US20030125304A1 (en) 2001-11-09 2003-07-03 Hans-Ulrich Demuth Substituted amino ketone compounds
US20030093697A1 (en) * 2001-11-13 2003-05-15 Lin Wen Chi Method for preventing unauthorized persons from entering and using a computer facility
US20030089935A1 (en) 2001-11-13 2003-05-15 Macronix International Co., Ltd. Non-volatile semiconductor memory device with multi-layer gate insulating structure
JP4771661B2 (en) 2001-11-26 2011-09-14 トラスティーズ オブ タフツ カレッジ Post-proline cleavage enzyme pseudopeptide inhibitor
IL161717A0 (en) 2001-11-26 2004-09-27 Schering Corp Piperidine-based mch antagonists for treatment of obesity and cns disorders
WO2003045228A2 (en) 2001-11-26 2003-06-05 Trustees Of Tufts College Methods for treating autoimmune disorders, and reagents related thereto
AU2002350217A1 (en) 2001-12-04 2003-06-17 Bristol-Myers Squibb Company Glycinamides as factor xa inhibitors
WO2003051841A2 (en) 2001-12-14 2003-06-26 Novo Nordisk A/S Compounds and uses thereof for decreasing activity of hormone-sensitive lipase
CZ2004747A3 (en) 2001-12-21 2004-11-10 Novo Nordisk A/S Amide derivatives functioning as GK activators
TW200301698A (en) 2001-12-21 2003-07-16 Bristol Myers Squibb Co Acridone inhibitors of IMPDH enzyme
WO2003055545A1 (en) * 2001-12-25 2003-07-10 Kaneka Corporation Adsorbent for cytokine, method of adsorptive removal, and apparatus for adsorptive removal
US6727261B2 (en) 2001-12-27 2004-04-27 Hoffman-La Roche Inc. Pyrido[2,1-A]Isoquinoline derivatives
EP1461070B1 (en) 2001-12-29 2007-01-24 Novo Nordisk A/S Combined use of a glp-1 compound and an aldose reductase inhibitor
WO2003057200A2 (en) 2002-01-11 2003-07-17 Novo Nordisk A/S Compositions comprising inhibitors of dpp-iv and nep enzymes for the treatment of diabetes
US7192601B2 (en) * 2002-01-18 2007-03-20 Walker Edward B Antimicrobial and sporicidal composition
US7101898B2 (en) 2002-02-01 2006-09-05 Novo Nordisk A/S Amides of aminoalkyl-substituted azetidines, pyrrolidines, piperidines and azepanes
AU2003218969A1 (en) 2002-02-01 2003-09-02 Probiodrug Ag Modulation of t lymphocytes using dp iv inhibitors
PL371678A1 (en) 2002-02-13 2005-06-27 F.Hoffmann-La Roche Ag Novel pyridin- and pyrimidin-derivatives
CA2474460C (en) 2002-02-13 2009-12-22 F. Hoffmann-La Roche Ag Pyridine- and quinoline-derivatives
KR20040095239A (en) 2002-02-27 2004-11-12 화이자 프로덕츠 인코포레이티드 Acc inhibitors
EP1480961B1 (en) 2002-02-28 2006-12-27 Prosidion Ltd. Glutaminyl based dpiv inhibitors
WO2003076418A1 (en) 2002-03-07 2003-09-18 X-Ceptor Therapeutics, Inc. Quinazolinone modulators of nuclear receptors
US20030232761A1 (en) 2002-03-28 2003-12-18 Hinke Simon A. Novel analogues of glucose-dependent insulinotropic polypeptide
US20040106802A1 (en) 2002-04-08 2004-06-03 Torrent Pharmaceuticals Ltd. Novel compounds and therapeutic uses thereof
CN1633420A (en) 2002-04-08 2005-06-29 托伦脱药品有限公司 Thiazolidine-4-carbonitriles and analogues and their use as dipeptidyl-peptidas inhibitors
JP2003300977A (en) * 2002-04-10 2003-10-21 Sumitomo Pharmaceut Co Ltd Xanthine derivative
EP1499336A4 (en) 2002-04-30 2005-06-01 Tufts College Protease inhibitors
TW200307667A (en) 2002-05-06 2003-12-16 Bristol Myers Squibb Co Sulfonylaminovalerolactams and derivatives thereof as factor Xa inhibitors
US7057046B2 (en) 2002-05-20 2006-06-06 Bristol-Myers Squibb Company Lactam glycogen phosphorylase inhibitors and method of use
US7034033B2 (en) 2002-05-23 2006-04-25 Chiron Corporation Substituted quinazolinone compounds
GB0212412D0 (en) 2002-05-29 2002-07-10 Novartis Ag Combination of organic compounds
WO2003101449A2 (en) 2002-06-04 2003-12-11 Pfizer Products Inc. Process for the preparation of 3,3,4,4-tetrafluoropyrrolidine and derivatives thereof
US6710040B1 (en) 2002-06-04 2004-03-23 Pfizer Inc. Fluorinated cyclic amides as dipeptidyl peptidase IV inhibitors
BR0311697A (en) 2002-06-06 2005-03-22 Eisai Co Ltd New Condensed Imidazole Derivatives
WO2003106628A2 (en) 2002-06-17 2003-12-24 Bristol-Myers Squibb Company Benzodiazepine inhibitors of mitochondial f1f0 atp hydrolase and methods of inhibiting f1f0 atp hydrolase
CA2489648A1 (en) 2002-06-17 2003-12-24 Smithkline Beecham Corporation Chemical process
SE0201976D0 (en) 2002-06-24 2002-06-24 Astrazeneca Ab Novel compounds
US20040054171A1 (en) 2002-07-04 2004-03-18 Jensen Anette Frost Polymorphic forms of a 4H-thieno[3,2-E]-1,2,4-thiadiazine 1,1-dioxide derivative
DK1528931T3 (en) 2002-08-09 2008-09-08 Prosidion Ltd Dipeptidyl peptidase IV inhibitors to reduce the rate of chronic weight gain
AU2003250471A1 (en) * 2002-08-13 2004-02-25 Warner-Lambert Company Llc Pyrimidine-2,4-dione derivatives as matrix metalloproteinase inhibitors
US7407955B2 (en) 2002-08-21 2008-08-05 Boehringer Ingelheim Pharma Gmbh & Co., Kg 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
EP2070539A1 (en) 2002-08-21 2009-06-17 Boehringer Ingelheim Pharma GmbH & Co. KG 8-[3-amino-piperidin-1-yl]-xanthins, their production and utilisation as medicine
US7495005B2 (en) 2002-08-22 2009-02-24 Boehringer Ingelheim Pharma Gmbh & Co. Kg Xanthine derivatives, their preparation and their use in pharmaceutical compositions
US6998502B1 (en) 2002-09-05 2006-02-14 Sabinsa Corporation Convenient process of manufacture for difluoromethylornithine and related compounds
EP1398032A1 (en) 2002-09-10 2004-03-17 PheneX Pharmaceuticals AG 4-Oxo-quinazolines as LXR nuclear receptor binding compounds
JP2004123738A (en) 2002-09-11 2004-04-22 Takeda Chem Ind Ltd Sustained-release preparation
US20040058876A1 (en) 2002-09-18 2004-03-25 Torsten Hoffmann Secondary binding site of dipeptidyl peptidase IV (DP IV)
ATE461212T1 (en) 2002-09-18 2010-04-15 Prosidion Ltd SECONDARY BINDING SITE OF DIPEPTIDYLPEPTIDASE IV (DP IV)
US7262207B2 (en) 2002-09-19 2007-08-28 Abbott Laboratories Pharmaceutical compositions as inhibitors of dipeptidyl peptidase-IV (DPP-IV)
US6869966B2 (en) 2002-09-30 2005-03-22 Banyu Pharmaceutical Co., Ltd. N-substituted-2-oxodihydropyridine derivatives
JP4352001B2 (en) 2002-10-18 2009-10-28 メルク エンド カムパニー インコーポレーテッド Beta-amino heterocyclic dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes
WO2004037176A2 (en) 2002-10-21 2004-05-06 Bristol-Myers Squibb Company Quinazolinones and derivatives thereof as factor xa inhibitors
ATE469645T1 (en) 2002-10-23 2010-06-15 Bristol Myers Squibb Co GLYCINENITRIL BASED INHIBITORS OF DIPEPTIDYLPEPTIDASE IV
US7482337B2 (en) 2002-11-08 2009-01-27 Boehringer Ingelheim Pharma Gmbh & Co. Kg Xanthine derivatives, the preparation thereof and their use as pharmaceutical compositions
MXPA05005260A (en) 2002-11-18 2005-07-25 Pfizer Prod Inc Dipeptidyl peptidase iv inhibiting fluorinated cyclic amides.
DE10254304A1 (en) 2002-11-21 2004-06-03 Boehringer Ingelheim Pharma Gmbh & Co. Kg New xanthine derivatives, their production and their use as medicines
US7109192B2 (en) 2002-12-03 2006-09-19 Boehringer Ingelheim Pharma Gmbh & Co Kg Substituted imidazo-pyridinones and imidazo-pyridazinones, the preparation thereof and their use as pharmaceutical compositions
DE10256264A1 (en) 2002-12-03 2004-06-24 Boehringer Ingelheim Pharma Gmbh & Co. Kg New trisubstituted dihydro-imidazo-pyridazinone or imidazo-pyridinone derivatives, useful as dipeptidylpeptidase-IV inhibitors for e.g. treating diabetes mellitus type I or II, arthritis or obesity
US7135467B2 (en) 2003-01-13 2006-11-14 Bristol-Myers Squibb Company HIV integrase inhibitors
US7148246B2 (en) 2003-02-27 2006-12-12 Sanofi-Aventis Deutschland Gmbh Cycloalkyl derivatives having bioisosteric carboxylic acid groups, processes for their preparation and their use as pharmaceuticals
US20050014732A1 (en) 2003-03-14 2005-01-20 Pharmacia Corporation Combination of an aldosterone receptor antagonist and an anti-diabetic agent
CN1894234A (en) 2003-03-25 2007-01-10 武田药品工业株式会社 Dipeptidyl peptidase inhibitors
TWI357408B (en) 2003-03-26 2012-02-01 Mitsubishi Tanabe Pharma Corp 3-substituted-4-pyrimidone derivatives
EP2206496B1 (en) 2003-05-05 2014-09-17 Probiodrug AG Screening of inhibitors of formation of pyroglutamic acid in amyloid beta peptide
WO2004099134A2 (en) 2003-05-05 2004-11-18 Prosidion Ltd. Glutaminyl based dp iv-inhibitors
WO2004098591A2 (en) * 2003-05-05 2004-11-18 Probiodrug Ag Inhibitors of glutaminyl cyclase and their use in the treatment of neurological diseases
EP1625122A1 (en) 2003-05-14 2006-02-15 Takeda San Diego, Inc. Dipeptidyl peptidase inhibitors
US7566707B2 (en) 2003-06-18 2009-07-28 Boehringer Ingelheim International Gmbh Imidazopyridazinone and imidazopyridone derivatives, the preparation thereof and their use as pharmaceutical compositions
MXPA05013734A (en) 2003-06-20 2006-03-08 Hoffmann La Roche Hexahydropyridoisoqinolines as dpp-iv inhibitors.
DE602004030244D1 (en) 2003-06-20 2011-01-05 Hoffmann La Roche ITOREN
JO2625B1 (en) 2003-06-24 2011-11-01 ميرك شارب اند دوم كوربوريشن Phosphoric acid salt of a dipeptidyl peptidase-IV inhibitor
NZ544747A (en) * 2003-07-07 2009-06-26 Neurocrine Biosciences Inc Pyrimidine-2, 4-dione derivatives as gonadotropin-releasing hormone receptor antagonists
JP4658044B2 (en) * 2003-07-07 2011-03-23 ニューロクライン バイオサイエンシーズ，インコーポレイテッド Pyrimidine-2,4-dione derivatives as gonadotropin releasing hormone receptor antagonists
ES2387495T3 (en) * 2003-07-07 2012-09-25 Neurocrine Biosciences, Inc. Arylpyrimidines useful in the treatment of disorders related to sex hormones, such as endometriosis, prostate cancer and the like
US6995183B2 (en) 2003-08-01 2006-02-07 Bristol Myers Squibb Company Adamantylglycine-based inhibitors of dipeptidyl peptidase IV and methods
MXPA06001601A (en) 2003-08-13 2006-08-25 Takeda Pharmaceutical 4-pyrimidone derivatives and their use as peptidyl peptidase inhibitors.
WO2005019168A2 (en) 2003-08-20 2005-03-03 Pfizer Products Inc. Fluorinated lysine derivatives as dipeptidyl peptidase iv inhibitors
WO2005026148A1 (en) 2003-09-08 2005-03-24 Takeda San Diego, Inc. Dipeptidyl peptidase inhibitors
US20050065144A1 (en) 2003-09-08 2005-03-24 Syrrx, Inc. Dipeptidyl peptidase inhibitors
US7238107B2 (en) 2003-09-29 2007-07-03 Mcvay Iii Julian Clyde Consonant pain
CN1918131B (en) * 2004-02-05 2011-05-04 前体生物药物股份公司 Novel inhibitors of glutaminyl cyclase
CN102079743B (en) 2004-03-15 2020-08-25 武田药品工业株式会社 Dipeptidyl peptidase inhibitors
ES2348667T3 (en) * 2004-07-02 2010-12-10 Corcept Therapeutics, Inc. MODULATORS OF MODIFIED PYRIMIDINE GLUCOCORTICOID RECEPTORS.
WO2006068978A2 (en) 2004-12-21 2006-06-29 Takeda Pharmaceutial Company Limited Dipeptidyl peptidase inhibitors
PL1931350T5 (en) 2005-09-14 2021-11-15 Takeda Pharmaceutical Company Limited Administration of dipeptidyl peptidase inhibitors
WO2007033350A1 (en) 2005-09-14 2007-03-22 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors for treating diabetes
TW200745079A (en) 2005-09-16 2007-12-16 Takeda Pharmaceuticals Co Polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile and methods of use therefor

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