[1,4]Diazepino[6,7,1-IJ]quinoline derivatives as antipsychotic and antiobesity agents

• US 20070004707A1
• Filed: 09/11/2006
• Published: 01/04/2007
• Est. Priority Date: 04/25/2002
• Status: Active Grant

• Current Assignee: P Ramamoorthy
• Original Assignee: P Ramamoorthy
• Inventors: Ramamoorthy, P.
• Granted Patent: US 7,687,620 B2
• Time in Patent Office: Days
• US Class Current: 514/220
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: C07D 471/06 Peri-condensed systems

Abstract

Compounds of Formula I or a pharmaceutically acceptable salt thereof are provided:
where R¹ through R⁷ are defined herein. The compounds of Formula I are 5HT2c agonists or partial agonists, and are useful for treating a variety of disorders.

Claims

1. A compound of Formula I or a pharmaceutically acceptable salt thereof:

2. The compound of claim 1 wherein, R² and R³ are independently hydrogen, halogen, cyano, perfluoroalkyl of 1 to 3 carbon atoms, phenyl or alkoxy of 1 to 3 carbon atoms.

3. The compound of claim 1, 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. The compound of claim 1, 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. The compound of claim 1, wherein R¹, R⁶ and R⁷ are hydrogen and n is 1.

6-18. -18. (canceled)

19. 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:

20. The method of claim 19, wherein the condition is schizophrenia.

21. The method of claim 19, wherein the mammal is human.

22. 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:

23. The method of claim 22, 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.

24. The method of claim 22, wherein the condition is depressive disorder, bipolar disorder or mood episode.

25. The method of claim 22, wherein the mammal is human.

26. 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:

27. The method of claim 26, wherein the condition is obesity.

28. The method of claim 26, wherein the mammal is a human.

29. 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:

30. A pharmaceutical composition comprising

a) at least one compound of Formula I or a pharmaceutically acceptable salt thereof:

wherein

R¹ is hydrogen or alkyl of 1 to 6 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, provided that when R⁴ and R⁵ are taken together to form the cyclic moiety, n is 2; and

a dotted line represents an optional double bond, provided that when R⁴ is hydrogen and R⁵ is hydrogen or alkyl of 1 to 6 carbon atoms, the optional double bond is present; and

b) at least one pharmaceutically acceptable carrier or excipient.

31. (canceled)