Aminopyridine dimer compounds, compositions and related methods for neuronal nitric oxide synthase inhibition
Nitric oxide synthase (NOS) inhibitor compounds comprising bi-terminal aromatic ring moieties, and related methods of NOS inhibition.
1. A nitric oxide synthase inhibitor compound of a formula
wherein each said X and each said Y is independently selected from CH and N, providing one of said X and Y in each said pair of X and Y is N; and Ar is selected from divalent aryl and heteroaryl linker moieties, and a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 where each of said Y is N.
3. The compound of claim 1 wherein Ar is selected from naphthyl, substituted naphthyl, phenyl, substituted phenyl, pyridinyl and substituted pyridinyl linker moieties.
4. The compound of claim 3 wherein Ar is selected from phenyl, substituted phenyl, pyridinyl and substituted pyridinyl linker moieties.
5. The compound of claim 4 wherein said terminal amino-substituted ring moieties have a meta-linkage to said Ar moiety.
6. The compound of claim 5 where Ar is selected from phenyl and pyridinyl moieties.
7. The compound of claim 5 wherein each of said Y is N.
8. The compound of claim 1 wherein said compound is an ammonium salt.
9. The compound of claim 8 wherein said salt has a counter ion that is conjugate base of a protic acid.
10. The compound of claim 1 complexed with a nitric oxide synthase enzyme.
11. A nitric oxide synthase inhibitor compound of a formula
wherein X and Y are independently selected from CH and N, providing at least one of X and Y is CH; and Z 1 and Z 2 are independently selected from CH and N, providing one of Z 1 and Z 2 is N; and a pharmaceutically acceptable salt thereof.
12. The compound of claim 11 wherein X is CH.
13. The compound of claim 12 wherein Y is N.
14. The compound of claim 11 wherein said amino-substituted terminal ring moieties have a meta-linkage.
15. The compound of claim 1 wherein said compound is an ammonium salt.
16. The compound of claim 1 complexed with a nitric oxide synthase enzyme.
17. A method of inhibiting a nitric oxide synthase comprising contacting a nitric oxide synthase with an effective amount of a compound of a formula
wherein each said X and each said Y is independently selected from CH and N, providing one of said X and Y in each said pair of X and Y is N; and Ar is selected from divalent aryl and heteroaryl linker moieties, and a pharmaceutically acceptable salt thereof.
18. The method of claim 17 wherein Ar is selected from phenyl, substituted phenyl, pyridinyl and substituted pyridinyl linker moieties.
19. The method of claim 18 wherein Ar is selected from phenyl and pyridinyl moieties.
20. The method of claim 19 wherein said amino-substituted terminal ring moieties have a meta-linkage to said Ar moiety, said method selective for inhibition of neuronal nitric oxide synthase.