Therapeutic agents useful for treating pain
The invention provides a compound of formula (I): (where R 1 , Q, A and R 2 are disclosed herein) or a pharmaceutically acceptable salt thereof (a “Pyridine-alkynyl Compound”); pharmaceutical compositions comprising an effective amount of a Pyridine-alkynyl Compound; and methods for treating or preventing a condition such as pain, urinary incontinence, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, a seizure, stroke, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, amyotrophic lateral sclerosis, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia or depression in an animal comprising administering to an animal in need thereof an effective amount of a Pyridine-alkynyl Compound.
1. A compound of formula (I):
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is -halo, —CH 3 , —CF 3 , —NO 2 , —CN or —H;
Q is:
R 3 and R 4 are independently —CH 2 —, —CH(CH 3 )— or —C(O)—;
J is —N(H)— or —O—;
A is —C(O)— or —CH 2 —;
R 2 is —(C 1 -C 6 )alkyl, —(C 3 -C 8 )cycloalkyl, -phenyl, -naphthyl, or —(C 14 )aryl, each of which is unsubstituted or substituted with one or more R 5 groups;
R 5 is -halo, —(C 1 -C 6 )alkyl, —(C 1 -C 6 )alkoxy or —OC(halo) 3 ;
a is 0 and b is 1;
each halo is independently —F, —Cl, —Br or —I; and
wherein the compound is optionally an optical isomer, a mixture of optical isomers, or a racemic mixture.
2. The compound of claim 1 , wherein A is —C(O)—.
3. The compound of claim 1 , wherein R 1 is —NO 2 .
4. The compound of claim 2 , wherein R 1 is —NO 2 .
5. The compound of claim 4 , wherein R 2 is -phenyl which is substituted with one or more R 5 groups.
6. The compound of claim 5 , wherein J is N(H), and R 3 and R 4 are each —CH 2 —.
7. The compound of claim 5 present as an optical isomer, wherein at least about 90 mol %, optionally at least about 95 mol %, of the compound is in the (S) form.
8. The compound of claim 5 present as an optical isomer, wherein at least about 90 mol %, optionally at least about 95 mol %, of the compound is in the (R) form.
9. The compound of claim 4 , wherein R 2 is -phenyl which is unsubstituted.
10. The compound of claim 9 , wherein J is N(H), and R 3 and R 4 are each —CH 2 —.
11. The compound of claim 9 present as an optical isomer, wherein at least about 90 mol %, optionally at least about 95 mol %, of the compound is in the (S) form.
12. The compound of claim 9 present as an optical isomer, wherein at least about 90 mol %, optionally at least about 95 mol %, of the compound is in the (R) form.
13. The compound of claim 1 , wherein at least one of R 3 or R 4 is —C(O)—.
14. The compound of claim 1 , wherein A is —CH 2 —.
15. The compound of claim 14 , wherein R 1 is —NO 2 and R 2 is -phenyl which is unsubstituted or substituted with one or more R 5 groups.
16. A compound of formula:
or a pharmaceutically acceptable salt thereof.
17. A composition comprising an effective amount of a compound or a pharmaceutically acceptable salt of the compound of claim 1 and a pharmaceutically acceptable carrier or excipient.
18. A composition comprising an effective amount of a compound or a pharmaceutically acceptable salt of the compound of claim 4 and a pharmaceutically acceptable carrier or excipient.
19. A composition comprising an effective amount of a compound or a pharmaceutically acceptable salt of the compound of claim 15 and a pharmaceutically acceptable carrier or excipient.
20. The compound of claim 5 , wherein J is O, and R 3 and R 4 are each —CH 2 —.
21. The compound of claim 9 , wherein J is O, and R 3 and R 4 are each —CH 2 —.
22. The compound of claim 2 , wherein R 1 is —CN.
23. The compound of claim 22 , wherein R 2 is -phenyl which is substituted with one or more R 5 groups.
24. The compound of claim 23 , wherein J is N(H), and R 3 and R 4 are each —CH 2 —.
25. The compound of claim 22 , wherein R 2 is -phenyl which is unsubstituted.
26. The compound of claim 25 , wherein J is N(H), and R 3 and R 4 are each —CH 2 —.
27. The compound of claim 15 , wherein J is N(H), and R 3 and R 4 are each —CH 2 —.