NOVEL BICYCLIC COMPOUNDS

• US 20130253029A1
• Filed: 09/27/2011
• Published: 09/26/2013
• Est. Priority Date: 09/28/2010
• Status: Active Grant

• Current Assignee: Panacea Biotec Limited
• Original Assignee: Panacea Biotec Limited
• Inventors: Jain, Rajesh, Trehan, Sanjay, Das, Jagattaran, Singh, Nishan, Sharma, Sudhir Kumar
• Granted Patent: US 9,133,116 B2
• Time in Patent Office: Days
• US Class Current: 514/412
• CPC Class Codes: A61K 31/403 condensed with carbocyclic rings, e.g. carbazole
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 209/52 condensed with a ring other than six-membered

Abstract

The present invention relates to novel compounds of Formula I, their pharmaceutically acceptable derivatives, tautomeric forms, isomers, polymorphs, prodrugs, metabolites, salts or solvates thereof. The invention also relates to processes for the synthesis of novel compounds of Formula I, their pharmaceutically acceptable derivatives, tautomeric forms, isomers, polymorphs, prodrugs, metabolites, salts or solvates thereof. The present invention further provides pharmaceutical compositions comprising compounds of Formula I and methods of treating or preventing one or more disorders of the central and/or peripheral nervous system, preferably by modulating neurological and/or psychiatric targets (GPCR and/or non-GPCR).

Claims

1. A compound of Formula I,

2. The compound according to claim 1 having the Formula Ia, wherein

3. The compound according to claim 1 having the Formula Ib, wherein

4. The compound according to claim 1, wherein R² and R³ are independently selected from —

H, C_1-12 alkyl, C_2-12 alkenyl, C_2-12 alkynyl, C_3-7 cycloalkyl, heterocyclyl, aryl, heteroaryl, each of which is unsubstituted or substituted, at any available position, with one or more substituents selected from —

F, —

Cl, —

Br, —

I, —

OH, —

OR^a, C_1-12 alkyl, C_3-7 cycloalkyl, aryl, heteroaryl.

5. The compound according to claim 1, wherein R³ is selected from —

H,

6. The compound according to claim 1, wherein R² is selected from —

H,

7. The compound according to claim 1, wherein R¹ is selected from —

H, C_1-12 alkyl, C_2-12 alkenyl, C_2-12 alkynyl, C_3-7 cycloalkyl, each of which is unsubstituted or substituted, at any available position, with one or more substituents selected from —

F, —

Cl, —

Br, —

I, —

OH, C_3-7 cycloalkyl, —

OR^a.

8. The compound according to claim 1, wherein R¹ is —

H or C_1-12 alkyl.

9. The compound according to claim 1, wherein Z is NOR⁴.

10. The compound according to claim 9, wherein R⁴ is selected from —

H, C_1-12 alkyl, C_2-12 alkenyl, C_2-12 alkynyl, C_3-7 cycloalkyl, heterocyclyl, aryl, heteroaryl, each of which is unsubstituted or substituted, at any available position, with one or more substituents selected from —

F, —

Cl, —

Br, —

I, C_3-7 cycloalkyl, heterocyclyl, aryl, heteroaryl, —

OH, —

OR^a, —

NR^aR^b;

with the proviso that when R⁴ is C_1-12 alkyl, then R² cannot be heterocyclyl or heteroaryl.

11. The compound according to claim 9, wherein R⁴ is selected from —

H, —

CH₃, —

C₂H₅, —

CH₂—

CH═

CH₂, —

C₆H₅, —

CH₂—

C₆H₅, —

(CH₂)₂—

OCH₃, —

(CH₂)₂—

NH₂,

15. A pharmaceutical composition, comprising a compound according to claim 1 or its pharmaceutically acceptable derivatives, tautomeric forms, isomers, polymorphs, prodrugs, metabolites, salts or solvates thereof, optionally in combination with one or more pharmaceutically acceptable carrier(s).

16. A pharmaceutical composition according to claim 15 useful for the prophylaxis, amelioration and/or treatment of one or more condition(s)/disease(s)/disorder(s) of the central and/or peripheral nervous system.

17. A pharmaceutical composition according to claim 15 useful for the prophylaxis, amelioration and/or treatment of one or more condition(s)/disease(s)/disorder(s) of the central and/or peripheral nervous system that are responsive to modulation of neurological and/or psychiatric targets (GPCR and/or non-GPCR).

18. A pharmaceutical composition according to claim 15 useful for the prophylaxis, amelioration and/or treatment of one or more condition(s)/disease(s)/disorder(s) of the central and/or peripheral nervous system that are responsive to modulation of biogenic amines and/or their receptors, in particular one or more, or any combination of serotonin, norepinephrine and dopamine.

19. A method for prophylaxis, amelioration and/or treatment of one or more condition(s)/disease(s)/disorder(s) of the central and/or peripheral nervous system, in a subject in need thereof, which comprises administering a therapeutically effective amount of compound according to claim 1 or pharmaceutically acceptable derivatives, tautomeric forms, isomers, polymorphs, prodrugs, metabolites, salts or solvates thereof.

20. A method for prophylaxis, amelioration and/or treatment of one or more condition(s)/disease(s)/disorder(s) of the central and/or peripheral nervous system that are responsive to modulation of neurological and/or psychiatric targets (GPCR and/or non-GPCR), in a subject in need thereof, which comprises administering a therapeutically effective amount of compound according to claim 1 or pharmaceutically acceptable derivatives, tautomeric forms, isomers, polymorphs, prodrugs, metabolites, salts or solvates thereof.

21. A method for prophylaxis, amelioration and/or treatment of one or more condition(s)/disease(s)/disorder(s) of the central and/or peripheral nervous system that are responsive to modulation of biogenic amines and/or their receptors, in particular one or more, or any combination of serotonin, norepinephrine and dopamine, in a subject in need thereof, which comprises administering a therapeutically effective amount of compound according to claim 1 or pharmaceutically acceptable derivatives, tautomeric forms, isomers, polymorphs, prodrugs, metabolites, salts or solvates thereof.

22. Use of a compound according to claim 1 or its pharmaceutically acceptable derivatives, tautomeric forms, isomers, polymorphs, prodrugs, metabolites, salts or solvates thereof, for the manufacture of a medicament for the prophylaxis, amelioration and/or treatment of one or more condition(s)/disease(s)/disorder(s) of the central and/or peripheral nervous system, in a subject in need thereof.

23. Use of a compound according to claim 1 or its pharmaceutically acceptable derivatives, tautomeric forms, isomers, polymorphs, prodrugs, metabolites, salts or solvates thereof, for the manufacture of a medicament for the prophylaxis, amelioration and/or treatment of one or more condition(s)/disease(s)/disorder(s) of the central and/or peripheral nervous system that are responsive to modulation of neurological and/or psychiatric targets (GPCR and/or non-GPCR), in a subject in need thereof.

24. Use of a compound according to claim 1 or its pharmaceutically acceptable derivatives, tautomeric forms, isomers, polymorphs, prodrugs, metabolites, salts or solvates thereof, for the manufacture of a medicament for the prophylaxis, amelioration and/or treatment of one or more condition(s)/disease(s)/disorder(s) of the central and/or peripheral nervous system that are responsive to modulation of biogenic amines and/or their receptors, in particular one or more, or any combination of serotonin, norepinephrine and dopamine, in a subject in need thereof.

25. Use of a compound according to claim 1 or its pharmaceutically acceptable derivatives, tautomeric forms, stereoisomers, polymorphs, prodrugs, metabolites, salts or solvates thereof, in combination with other therapeutic agents.

26. Use according to claim 22 wherein the medicament is administered orally, parenterally or topically.

12. A compound which is selected from the group consisting of:

13. A compound which is selected from the group consisting of:

14. A compound of Formula V,

27. The compounds of Formula I, methods and compositions as described and illustrated herein.