CA2481321A1 - [1,4]diazepino[6,7,1-ij]quinoline derivatives as antipsychotic and antiobesity agents - Google Patents
[1,4]diazepino[6,7,1-ij]quinoline derivatives as antipsychotic and antiobesity agents Download PDFInfo
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- C07D487/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains four or more hetero rings
Abstract
Compounds of formula 1 or a pharmaceutically acceptable salt thereof are provided: I where R1 through R7 are defined herein. The compounds of formula I are 5HT2c agonists or partial agonists, and are useful for treating a variet y of disorders.
Claims (34)
1. A compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R1 is hydrogen, alkyl of 1 to 6 carbon atoms, alkanoyl of 2 to 6 carbon atoms, or carboarylalkoxy of 7 to 11 carbon atoms;
R2 and R3 are each, independently, hydrogen, hydroxy, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, carboxamido, carboalkoxy of two to six carbon atoms, perfluoroalkyl of 1-6 carbon atoms, cyano, alkanesulfonamido of 1-6 carbon atoms, alkanesulfonyl of 1-6 carbon atoms, alkanamido of 1-6 carbon atoms, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 1-6 carbon atoms per alkyl moiety, perfluoroalkoxy of 1-6 carbon atoms, alkanoyloxy of 2 to 6 carbon atoms, alkanoyl of 2 to 6 carbon atoms, aroyl of 6 to 8 carbon atoms, aryl of 5 to 7 carbon atoms, a C6 to C13 alkylaryl group having 5 to 7 carbon atoms in the aryl moiety, a 5 to 7 membered heteroaryl group, or a 6 to 13 membered alkylheteroaryl group having 5 to 7 members in the heteroaryl moiety, wherein any R2 or R3 substituent having an aryl or heteroaryl moiety may optionally be substituted on the aryl or heteroaryl moiety with 1 to 3 substituents independently selected from a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group;
R4 and R5 are, independently, hydrogen or alkyl of 1 to 6 carbon atoms, or R4 and R5, taken together with the carbons to which they are attached, form a cyclic moiety selected from a cycloalkane of 4 to 8 carbon atoms, cycloalkene of 4 to 8 carbon atoms, bridged bicyclic alkane of 5 to 10 carbon atoms, bridged bicyclic alkene of 5 to 10 carbon atoms, pyran or thiopyran in which the sulfur atom is optionally oxidized to the sulfoxide or sulfone, wherein the cyclic moiety formed by R4 and R5 may optionally be substituted with 1 to 3 substituents independently selected from a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group;
R6 and R7 are each, independently, hydrogen or alkyl of 1 to 6 carbon atoms;
n is 1 or 2; and a dotted line represents an optional double bond.
wherein R1 is hydrogen, alkyl of 1 to 6 carbon atoms, alkanoyl of 2 to 6 carbon atoms, or carboarylalkoxy of 7 to 11 carbon atoms;
R2 and R3 are each, independently, hydrogen, hydroxy, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, carboxamido, carboalkoxy of two to six carbon atoms, perfluoroalkyl of 1-6 carbon atoms, cyano, alkanesulfonamido of 1-6 carbon atoms, alkanesulfonyl of 1-6 carbon atoms, alkanamido of 1-6 carbon atoms, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 1-6 carbon atoms per alkyl moiety, perfluoroalkoxy of 1-6 carbon atoms, alkanoyloxy of 2 to 6 carbon atoms, alkanoyl of 2 to 6 carbon atoms, aroyl of 6 to 8 carbon atoms, aryl of 5 to 7 carbon atoms, a C6 to C13 alkylaryl group having 5 to 7 carbon atoms in the aryl moiety, a 5 to 7 membered heteroaryl group, or a 6 to 13 membered alkylheteroaryl group having 5 to 7 members in the heteroaryl moiety, wherein any R2 or R3 substituent having an aryl or heteroaryl moiety may optionally be substituted on the aryl or heteroaryl moiety with 1 to 3 substituents independently selected from a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group;
R4 and R5 are, independently, hydrogen or alkyl of 1 to 6 carbon atoms, or R4 and R5, taken together with the carbons to which they are attached, form a cyclic moiety selected from a cycloalkane of 4 to 8 carbon atoms, cycloalkene of 4 to 8 carbon atoms, bridged bicyclic alkane of 5 to 10 carbon atoms, bridged bicyclic alkene of 5 to 10 carbon atoms, pyran or thiopyran in which the sulfur atom is optionally oxidized to the sulfoxide or sulfone, wherein the cyclic moiety formed by R4 and R5 may optionally be substituted with 1 to 3 substituents independently selected from a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group;
R6 and R7 are each, independently, hydrogen or alkyl of 1 to 6 carbon atoms;
n is 1 or 2; and a dotted line represents an optional double bond.
2. A compound according to Claim 1 wherein, R2 and R3 independently, are hydrogen, halogen, cyano, perfluoroalkyl of 1 to 3 carbon atoms, phenyl or alkoxy of 1 to 3 carbon atoms.
3. A compound according to Claim 1 or Claim 2 wherein R4 and R5 are taken together, along with the carbon atoms to which they are attached, to form a cycloalkane or cycloalkene moiety of 5 to 8 carbon atoms, where one or more of the carbon atoms are optionally substituted by alkyl of 1 to 4 carbon atoms.
4. A compound according to Claim 1 or Claim 2 wherein R4 and R5 are taken together, along with the carbon atoms to which they are attached, to form a cycloalkane moiety of 5 to 7 carbon atoms.
5. A compound according to any one of Claims 1 to 4 wherein at least one of R1, R6 and R7 is hydrogen.
6. A compound according to any one of Claims 1 to 5 wherein R1, R6 and R7 are all hydrogen.
7. A compound according to any one of Claims 1 to 6 wherein n is 1.
8. A compound according to Claim 1 wherein R2 and R3 are independently selected from hydrogen, halo, trifluoromethyl, phenyl or alkoxy of 1 to 3 carbon atoms; R1, R6 and R7 are each hydrogen; n is 1; and R4 and R5, taken together with the carbon atoms to which they are attached, form cyclopentane, cyclohexane or cycloheptane.
9. A compound according to Claim 1 which is one of the following:
4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino[6,7,1-ij]-quinoline;
2-bromo-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino-[6,7,1-ij]quinoline hydrochloride 2-chloro-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino-[6,7,1-ij]quinoline hydrochloride;
2-phenyl-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino-[6,7,1-ij]quinoline hydrochloride;
2-methoxy-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino-[6,7,1-ij]quinoline hydrochloride;
1-fluoro-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino-[6,7,1-ij]quinoline hydrochloride;
1-(trifluoromethyl)-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]-diazepino[6,7,1-ij]quinoline hydrochloride;
1-fluoro-2-methoxy-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]-diazepino[6,7,1-ij]quinoline hydrochloride;
or pharmaceutically acceptable salts thereof.
4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino[6,7,1-ij]-quinoline;
2-bromo-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino-[6,7,1-ij]quinoline hydrochloride 2-chloro-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino-[6,7,1-ij]quinoline hydrochloride;
2-phenyl-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino-[6,7,1-ij]quinoline hydrochloride;
2-methoxy-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino-[6,7,1-ij]quinoline hydrochloride;
1-fluoro-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino-[6,7,1-ij]quinoline hydrochloride;
1-(trifluoromethyl)-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]-diazepino[6,7,1-ij]quinoline hydrochloride;
1-fluoro-2-methoxy-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]-diazepino[6,7,1-ij]quinoline hydrochloride;
or pharmaceutically acceptable salts thereof.
10. A compound according to Claim 1 which is 4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino[6,7,1-ij]-quinoline or a pharmaceutically acceptable salt thereof.
11. A compound according to Claim 1 which is (-)-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino[6,7,1-ij]quinoline, or a pharmaceutically acceptable salt thereof.
12. A compound according to Claim 1 which is 4,5,6,7,9a,10,11,12,13,13a-deca-hydro-9H-[1,4]diazepino[6,7,1-de]phenanthridine hydrochloride or a pharmaceutically acceptable salt thereof.
13. A compound according to Claim 1 which is one of the following:
4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclohepta[c][1,4]diazepino-[6,7,1-ij]quinoline;
2-bromo-4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclohepta[c][1,4]-diazepino[6,7,1-ij]quinoline hydrochloride;
2-chloro-4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclohepta[c][1,4]-diazepino[6,7,1-ij]quinoline hydrochloride;
1-fluoro-4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclohepta[c][1,4]-diazepino[6,7,1-ij]quinoline hydrochloride;
1-fluoro-2-methoxy-4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclohepta-[c][1,4]diazepino[6,7,1-ij]quinoline hydrochloride;
or a pharmaceutically acceptable salt thereof.
4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclohepta[c][1,4]diazepino-[6,7,1-ij]quinoline;
2-bromo-4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclohepta[c][1,4]-diazepino[6,7,1-ij]quinoline hydrochloride;
2-chloro-4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclohepta[c][1,4]-diazepino[6,7,1-ij]quinoline hydrochloride;
1-fluoro-4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclohepta[c][1,4]-diazepino[6,7,1-ij]quinoline hydrochloride;
1-fluoro-2-methoxy-4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclohepta-[c][1,4]diazepino[6,7,1-ij]quinoline hydrochloride;
or a pharmaceutically acceptable salt thereof.
14. A compound according to Claim 1 which is 4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclohepta[c][1,4]diazepino-[6,7,1-ij]quinoline; or a pharmaceutically acceptable salt thereof.
15. A compound according to Claim 1 which is one of the following:
(9aR,14aS)-4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclohepta[c][1,4]-diazepino[6,7,1-ij]quinoline hydrochloride;
(9aS,14aR)-4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclohepta[c][1,4]-diazepino[6,7,1-ij]quinoline hydrochloride;
or pharmaceutically acceptable salts thereof.
(9aR,14aS)-4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclohepta[c][1,4]-diazepino[6,7,1-ij]quinoline hydrochloride;
(9aS,14aR)-4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclohepta[c][1,4]-diazepino[6,7,1-ij]quinoline hydrochloride;
or pharmaceutically acceptable salts thereof.
16. A compound according to Claim 1 which is one of the following:
5-acetyl-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino-[6,7,1-ij]quinoline;
benzyl 2-bromo-6,7,9,9a,10,11,12,12a-octahydrocyclopenta[c][1,4]diazepino-[6,7,1-ij]quinoline-5(4H)-carboxylate;
benzyl 2-chloro-6,7,9,9a,10,11,12,12a-octahydrocyclopenta[c][1,4]diazepino-[6,7,1-ij]quinoline-5(4H)-carboxylate;
benzyl 2-phenyl-6,7,9,9a,10,11,12,12a-octahydrocyclopenta[c][1,4]diazepino-[6,7,1-ij]quinoline-5(4H)-carboxylate;
benzyl 2-methoxy-6,7,9,9a,10,11,12,12a-octahydrocyclopenta[c][1,4]-diazepino[6,7,1-ij]quinoline-5(4H)-carboxylate;
benzyl 1-fluoro-6,7,9,9a,10,11,12,12a-octahydrocyclopenta[c][1,4]diazepino-[6,7,1-ij]quinoline-5(4H)-carboxylate;
benzyl 1-(trifluoromethyl)-6,7,9,9a,10,11,12,12a-octahydrocyclopenta[c][1,4]-diazepino[6,7,1-ij]quinoline-5(4H)-carboxylate;
or pharmaceutically acceptable salts thereof.
5-acetyl-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino-[6,7,1-ij]quinoline;
benzyl 2-bromo-6,7,9,9a,10,11,12,12a-octahydrocyclopenta[c][1,4]diazepino-[6,7,1-ij]quinoline-5(4H)-carboxylate;
benzyl 2-chloro-6,7,9,9a,10,11,12,12a-octahydrocyclopenta[c][1,4]diazepino-[6,7,1-ij]quinoline-5(4H)-carboxylate;
benzyl 2-phenyl-6,7,9,9a,10,11,12,12a-octahydrocyclopenta[c][1,4]diazepino-[6,7,1-ij]quinoline-5(4H)-carboxylate;
benzyl 2-methoxy-6,7,9,9a,10,11,12,12a-octahydrocyclopenta[c][1,4]-diazepino[6,7,1-ij]quinoline-5(4H)-carboxylate;
benzyl 1-fluoro-6,7,9,9a,10,11,12,12a-octahydrocyclopenta[c][1,4]diazepino-[6,7,1-ij]quinoline-5(4H)-carboxylate;
benzyl 1-(trifluoromethyl)-6,7,9,9a,10,11,12,12a-octahydrocyclopenta[c][1,4]-diazepino[6,7,1-ij]quinoline-5(4H)-carboxylate;
or pharmaceutically acceptable salts thereof.
17. A compound according to Claim 1 which is one of the following:
(-)-5-acetyl-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino-[6,7,1-ij]quinoline;
(+)-5-acetyl-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino-[6,7,1-ij]quinoline;
or pharmaceutically acceptable salts thereof.
(-)-5-acetyl-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino-[6,7,1-ij]quinoline;
(+)-5-acetyl-4,5,6,7,9,9a,10,11,12,12a-decahydrocyclopenta[c][1,4]diazepino-[6,7,1-ij]quinoline;
or pharmaceutically acceptable salts thereof.
18. A compound according to Claim 1 which is benzyl 6,7,9a,10,11,12,13,13a-octahydro-9H-[1,4]diazepino[6,7,1-de]phenanthridine-5(4H)-carboxylate; or a pharmaceutically acceptable salt thereof.
19. A compound according to Claim 1 which is one of the following:
5-acetyl-4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclohepta[c][1,4]-diazepino[6,7,1-ij]quinoline;
benzyl 2-bromo-6,7,9,9a,10,11,12,13,14,14a-decahydrocyclohepta[c][1,4]-diazepino[6,7,1-ij]quinoline-5(4H)-carboxylate;
benzyl 2-chloro-6,7,9,9a,10,11,12,13,14,14a-decahydrocyclohepta[c][1,4]-diazepino[6,7,1-ij]quinoline-5(4H)-carboxylate;
benzyl 1-fluoro-6,7,9,9a,10,11,12,13,14,14a-decahydrocyclohepta[c][1,4]-diazepino[6,7,1-ij]quinoline-5(4H)-carboxylate;
benzyl 1-fluoro-2-methoxy-6,7,9,9a,10,11,12,13,14,14a-decahydrocyclo-hepta[c][1,4]diazepino[6,7,1-ij]quinoline-5(4H)-carboxylate;
or pharmaceutically acceptable salts thereof.
5-acetyl-4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclohepta[c][1,4]-diazepino[6,7,1-ij]quinoline;
benzyl 2-bromo-6,7,9,9a,10,11,12,13,14,14a-decahydrocyclohepta[c][1,4]-diazepino[6,7,1-ij]quinoline-5(4H)-carboxylate;
benzyl 2-chloro-6,7,9,9a,10,11,12,13,14,14a-decahydrocyclohepta[c][1,4]-diazepino[6,7,1-ij]quinoline-5(4H)-carboxylate;
benzyl 1-fluoro-6,7,9,9a,10,11,12,13,14,14a-decahydrocyclohepta[c][1,4]-diazepino[6,7,1-ij]quinoline-5(4H)-carboxylate;
benzyl 1-fluoro-2-methoxy-6,7,9,9a,10,11,12,13,14,14a-decahydrocyclo-hepta[c][1,4]diazepino[6,7,1-ij]quinoline-5(4H)-carboxylate;
or pharmaceutically acceptable salts thereof.
20. A compound according to Claim 1 which is one of the following:
(9aR,14aS)-5-acetyl-4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclo-hepta[c][1,4]diazepino[6,7,1-ij]quinoline;
(9aS,14aR)-5-acetyl-4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclo-hepta[c][1,4]diazepino[6,7,1-ij]quinoline;
or pharmaceutically acceptable salts thereof.
(9aR,14aS)-5-acetyl-4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclo-hepta[c][1,4]diazepino[6,7,1-ij]quinoline;
(9aS,14aR)-5-acetyl-4,5,6,7,9,9a,10,11,12,13,14,14a-dodecahydrocyclo-hepta[c][1,4]diazepino[6,7,1-ij]quinoline;
or pharmaceutically acceptable salts thereof.
21. A method of treating a mammal suffering from a condition selected from schizophrenia, schizophreniform disorder, schizoaffective disorder, delusional disorder, substance-induced psychotic disorder, L-DOPA-induced psychosis, psychosis associated with Alzheimer's dementia, psychosis associated with Parkinson's disease, psychosis associated with Lewy body disease, dementia, memory deficit, or intellectual deficit disorder associated with Alzheimer's disease comprising providing to the mammal suffering from the condition, a therapeutically effective amount of at least one compound of formula I or a pharmaceutically acceptable salt thereof as claimed in any one of Claims 1 to 20.
22. A method according to Claim 21 wherein the condition is schizophrenia.
23. A method according to Claim 21 or Claim 22 wherein the mammal is human.
24. A method of treating a mammal suffering from a condition selected from bipolar disorders, depressive disorders, mood episodes, anxiety disorders, adjustment disorders, or eating disorders comprising providing to the mammal suffering from the condition, a therapeutically effective amount of at least one compound of formula I or a pharmaceutically acceptable salt thereof as claimed in any one of Claims 1 to 20.
25. A method according to Claim 24 wherein the bipolar disorder is bipolar I
disorder, bipolar II disorder, or cyclothymic disorder; the depressive disorder is major depressive disorder, dysthymic disorder, or substance-induced mood disorder;
the mood episode is major depressive episode, manic episode, mixed episode, or hypomanic episode; the anxiety disorder is panic attack, agoraphobia, panic disorder, specific phobia, social phobia, obsessive compulsive disorder, posttraumatic stress disorder, acute stress disorder, generalized anxiety disorder, separation anxiety disorder, or substance-induced anxiety disorder.
disorder, bipolar II disorder, or cyclothymic disorder; the depressive disorder is major depressive disorder, dysthymic disorder, or substance-induced mood disorder;
the mood episode is major depressive episode, manic episode, mixed episode, or hypomanic episode; the anxiety disorder is panic attack, agoraphobia, panic disorder, specific phobia, social phobia, obsessive compulsive disorder, posttraumatic stress disorder, acute stress disorder, generalized anxiety disorder, separation anxiety disorder, or substance-induced anxiety disorder.
26. A method according to Claim 24 wherein the condition is depressive disorder, bipolar disorder or mood episode.
27. A method according to any one of Claims 24 to 26 wherein the mammal is human.
28. A method of treating a mammal suffering from a condition selected from epilepsy, sleep disorders, migraines, sexual dysfunction, gastrointestinal disorders, or obesity comprising providing to the mammal suffering from the condition, a therapeutically effective amount of at least one compound of formula I or a pharmaceutically acceptable salt thereof as claimed in any one of Claims 1 to 20.
29. A method according to Claim 28 wherein the condition is obesity.
30. A method according to Claim 28 or Claim 29 wherein the mammal is a human.
31. A method of treating a mammal suffering from a central nervous system deficiency associated with trauma, stroke, or spinal cord injury comprising providing to the mammal suffering from the condition, a therapeutically effective amount of at least one compound of formula I or a pharmaceutically acceptable salt thereof as claimed in any one of Claims 1 to 20.
32. A pharmaceutical composition comprising at least one compound of formula I
or a pharmaceutically acceptable salt thereof as claimed in any one of Claims 1 to 20, and at least one pharmaceutically acceptable carrier or excipient.
or a pharmaceutically acceptable salt thereof as claimed in any one of Claims 1 to 20, and at least one pharmaceutically acceptable carrier or excipient.
33. A composition according to Claim 32 wherein R2 and R3 are independently selected from hydrogen, halo, trifluoromethyl, phenyl or alkoxy of 1 to 3 carbon atoms; R1, R6 and R7 are each hydrogen; n is 1; and R4 and R5, taken together with the carbon atoms to which they are attached, form cyclopentane, cyclohexane or cycloheptane.
34. A process for preparing a compound of formula I as claimed in Claim 1 which comprises one of the following:
(a) reacting a compound of formula IIA
wherein n, R2, R3 , R6 and R7 are as defined in Claim 1 and R represents alkyl of 1 to carbon atoms or arylalkoxy of 6 to 10 carbon atoms , with a compound of formula IIIA or IIIB:
wherein R4 and R5 are as defined in Claim 1, to give a corresponding compound of formula I wherein the dotted line is an optional bond, R1 is alkanoyl of 2 to 6 carbon atoms or carboarylalkoxy of 7 to 11 carbon atoms;
or (b) cyclising a compound of formula IVA
wherein R2 to R7 are as defined in Claim 1 with formaldehyde to give a compound of formula I as defined in Claim 1 wherein n is 1 and R1 is hydrogen;
(c) alkylating a compound of formula I as defined in Claim 1 wherein R1 is hydrogen to give a compound of formula I wherein R1 is alkyl of 1 to 6 carbon atoms;
or (d) acylating a compound of formula I as defined in Claim 1 wherein R1 is hydrogen to give a compound of formula I wherein R1 is alkanoyl of 2 to 6 carbon atoms or carboarylalkoxy of 7 to 11 carbon atoms;
or (e) hydrolysing a compound of formula I as defined in Claim 1 wherein R1 is alkanoyl of 2 to 6 carbon atoms or carboarylalkoxy of 7 to 11 carbon atoms, to give a corresponding compound of formula I wherein R1 is hydrogen;
or (f) converting a basic compound of formula I to a pharmaceutically acceptable salt thereof, or vice versa;
or (g) separating an enantiomeric or diastereomeric form of a compound of formula I from a mixture thereof.
(a) reacting a compound of formula IIA
wherein n, R2, R3 , R6 and R7 are as defined in Claim 1 and R represents alkyl of 1 to carbon atoms or arylalkoxy of 6 to 10 carbon atoms , with a compound of formula IIIA or IIIB:
wherein R4 and R5 are as defined in Claim 1, to give a corresponding compound of formula I wherein the dotted line is an optional bond, R1 is alkanoyl of 2 to 6 carbon atoms or carboarylalkoxy of 7 to 11 carbon atoms;
or (b) cyclising a compound of formula IVA
wherein R2 to R7 are as defined in Claim 1 with formaldehyde to give a compound of formula I as defined in Claim 1 wherein n is 1 and R1 is hydrogen;
(c) alkylating a compound of formula I as defined in Claim 1 wherein R1 is hydrogen to give a compound of formula I wherein R1 is alkyl of 1 to 6 carbon atoms;
or (d) acylating a compound of formula I as defined in Claim 1 wherein R1 is hydrogen to give a compound of formula I wherein R1 is alkanoyl of 2 to 6 carbon atoms or carboarylalkoxy of 7 to 11 carbon atoms;
or (e) hydrolysing a compound of formula I as defined in Claim 1 wherein R1 is alkanoyl of 2 to 6 carbon atoms or carboarylalkoxy of 7 to 11 carbon atoms, to give a corresponding compound of formula I wherein R1 is hydrogen;
or (f) converting a basic compound of formula I to a pharmaceutically acceptable salt thereof, or vice versa;
or (g) separating an enantiomeric or diastereomeric form of a compound of formula I from a mixture thereof.
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2004
- 2004-10-06 CR CR7510A patent/CR7510A/en unknown
- 2004-10-21 NO NO20044501A patent/NO329505B1/en not_active IP Right Cessation
- 2004-10-22 EC EC2004005379A patent/ECSP045379A/en unknown
- 2004-11-24 ZA ZA200409501A patent/ZA200409501B/en unknown
-
2005
- 2005-03-08 HK HK05101986A patent/HK1069388A1/en not_active IP Right Cessation
-
2006
- 2006-09-11 US US11/518,216 patent/US7687620B2/en not_active Expired - Fee Related
-
2008
- 2008-08-25 CY CY20081100902T patent/CY1108286T1/en unknown
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