2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
Various 2-aminoquinoline compounds as can be used, in vivo or in vitro, for selective inhibition of neuronal nitric oxide synthase.
1. A compound of a formula
wherein n is an integer selected from 1-2; m is an integer selected from 1-3; R is selected from chloro and fluoro groups; and o is an integer selected from 0-2, or a salt thereof.
2. The compound of claim 1 wherein the sum of n and m is 4-5.
3. The compound of claim 1 wherein R is F, and o is 1.
4. The compound of claim 3 wherein F is meta to said alkyleneamine moiety.
5. The compound of claim 1 wherein said quinoline moiety is substituted at the 7-position thereof, with said arylalkyleneaminealkylene moiety.
6. The compound of claim 1 wherein said compound is an ammonium salt.
7. The compound of claim 6 wherein said salt has a counter ion that is the conjugate base of a protic acid.
8. A compound of a formula
wherein n is an integer selected from 1-2; m is an integer selected from 1-3; R is selected from chloro and fluoro groups; and o is an integer selected from 0-2, or a salt thereof.
9. The compound of claim 8 wherein the sum of n and m is 4-5.
10. The compound of claim 9 wherein R is F, and o is 1.
11. The compound of claim 10 wherein F is meta to said alkyleneamine moiety.
12. The compound of claim 8 wherein said compound is an ammonium salt.
13. The compound of claim 12 wherein said salt has a counter ion that is the conjugate base of protic acid.
14. A compound of a formula
wherein n is an integer selected from 1-2; m is an integer from 2-3, providing where m is 3, n is 1; and R is selected from Cl and F, or a salt thereof.
15. The compound of claim 14 wherein the sum of n and m is 4.
16. The compound of claim 15 wherein R is F.
17. The compound of claim 14 wherein said compound is an ammonium salt.
18. The compound of claim 17 wherein said salt has a counter ion that is the conjugate base of a protic acid.
19. A method of modulating nitric oxide synthase activity, said method comprising contacting a nitric oxide synthase with an effective amount of a compound of claim 8 .
20. The method of claim 19 wherein the sum of n and m is 4-5.
21. The method of claim 20 wherein R is meta to the alkyleneamine moiety of said compound.
22. A method of inhibiting a nitric oxide synthase, said method comprising:
providing a compound of claim 14 ; and
contacting said compound with a nitric oxide synthase, said compound in an amount effective to inhibit nitric oxide synthase activity, thereby reducing nitric oxide production.
23. The method of claim 22 wherein the sum of n and m is 4.
24. The method of claim 23 selective for inhibition of neuronal nitric oxide synthase.
25. The method of claim 22 wherein said compound is provided in a pharmaceutical composition.
26. A compound of a formula
wherein X is selected from O and NH; Y is selected from CH and N; n is an integer selected from 1-2; m is an integer selected from 0-3; o is an integer selected from 0-3; and each R is independently selected from halo, alkyl, haloalkyl, alkoxy, cyano, amino, N-alkylamino, N,N-dialkylamino, aminealkyl, N-substituted and oxa-substituted aminealkyl moieties, or a salt thereof.
27. The compound of claim 26 wherein X is NH and Y is CH.
28. The compound of claim 27 wherein n is 1 and m is 0-1.
29. The compound of claim 26 wherein R is selected from fluoro, chloro, cyano, methoxy, N-alkylamine, N,N-dialkylamine, alkyl, aminealkyl, N-alkylaminealkyl and N,N-dialkylaminealkyl moieties.
30. The compound of claim 26 wherein X is O.
31. The compound of claim 30 wherein n is 1 and m is 0.
32. The compound of claim 31 wherein R is selected from fluoro, chloro, cyano, methoxy, N-methylamine, N,N-dimethylamine, alkyl, aminealkyl, N-methylaminealkyl and N,N-dimethylaminealkyl moieties.
33. The compound of claim 30 wherein Y is N and R is selected from N-methylaminealkyl and N,N-dimethylaminealkyl moieties.
34. A compound of a formula
wherein R 1 and R 2 are independently selected from H and methyl moieties; R 3 is selected from halo, alkyl, haloalkyl, alkoxy, cyano, amine, N-methylamine, N,N-dimethylamine, alkyl, aminealkyl, N-methylaminealkyl and N,N-dimethylaminealkyl moieties; n is an integer selected from 0-3; and each R 4 is independently selected from H and methyl moieties, or a salt thereof.
35. The compound of claim 34 wherein R 3 is selected from halo and cyano moieties.