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; each R is selected from halo, alkyl, haloalkyl, alkoxy, cyano, amino, N-alkylamino, N,N-dialkylamino, aminealkyl, N-substituted and oxa-substituted aminealkyl moieties; o is an integer selected from 0-3; and R′ is selected from H and alkyl, or a salt thereof.
2. The compound of claim 1 wherein the sum of n and m is 2-3.
3. The compound of claim 1 wherein o is 1, and R is cyano.
4. The compound of claim 1 wherein o is 2, and R is selected from a combination of halo, alkyl and cyano moieties.
5. The compound of claim 4 wherein one said R is meta to said alkyleneamine moiety, and one said R is para to said alkyleneamine moiety.
6. The compound of claim 1 wherein said quinoline moiety is substituted at the 7-position thereof, with said arylalkyleneaminealkylene moiety.
7. The compound of claim 1 wherein said compound is an ammonium salt.
8. The compound of claim 7 wherein said salt has a counter ion that is the conjugate base of a protic acid.
9. 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; each of R 1 and R 2 is independently selected from H, halo, alkyl and cyano moieties; and R′ is selected from H and methyl moieties, or a salt thereof.
10. The compound of claim 9 wherein the sum of n and m is 2-3.
11. The compound of claim 10 wherein one of said R 1 and R 2 is cyano and the other is H.
12. The compound of claim 11 wherein the sum of n and m is 2.
13. The compound of claim 9 wherein R′ is methyl.
14. The compound of claim 13 wherein one of said R 1 and R 2 is not H.
15. The compound of claim 9 wherein said compound is an ammonium salt.
16. The compound of claim 15 wherein said salt has a counter ion that is the conjugate base of a protic acid.
17. A compound of a formula
wherein X is NH; Y is CH; 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; and R′ is selected from H and alkyl, or a salt thereof.
18. The compound of claim 17 wherein n is 1 and m is 2-3.
19. The compound of claim 17 wherein R′ is methyl and said quinolone moiety is substituted at the 4-position thereof.
20. The compound of claim 19 wherein n is 1 and m is 2-3.
21. 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 1 .
22. The method of claim 21 wherein the sum of n and m is 2-3.
23. The method of claim 22 wherein o is 2, and R is selected from a combination of halo, alkyl and cyano moieties.
24. The method of claim 23 wherein one said R is meta to the alkyleneamine moiety, and one said R is para to said alkyleneamine moiety.
25. A method of inhibiting a nitric oxide synthase, said method comprising: providing a compound of claim 9 ; 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.
26. The method of claim 25 wherein the sum of n and m is 2-3.
27. The method of claim 26 selective for inhibition of neuronal nitric oxide synthase.
28. The method of claim 27 wherein said compound is provided in a pharmaceutical composition.