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 R is selected from H, halogen, amino, nitrile, alkyl, haloalkyl, aminoalkyl, cyanoalkyl, cycloalkyl and azacycloalkyl moieties; X and Y are independently selected from CR′ and N, where R′ is selected from H and R, and providing at least one of X and Y is CR; 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 salt thereof.
2. The compound of claim 1 wherein each of X and Y is CR′.
3. The compound of claim 2 wherein X is CH and Y is CR, and each said pendent aminopyridine moiety has a relationship to CR selected from ortho and meta-relationships.
4. The compound of claim 3 wherein each said relationship is meta.
5. The compound of claim 4 wherein R is selected from nitrile and aminoalkyl moieties.
6. The compound of claim 1 wherein Y is N, and said pendent aminopyridine moieties have a meta-relationship one to another.
7. The compound of claim 6 wherein X is CH, and R is selected from H, nitrile and aminoalkyl moieties.
8. The compound of claim 6 wherein X is CR′ and R′ is selected from H, nitrile and aminoalkyl moieties.
9. The compound of claim 1 wherein said compound is an ammonium salt.
10. The compound of claim 9 wherein said salt has a counter ion that is a conjugate of a protic acid.
11. A compound of a formula
wherein R is selected from H, halogen, amino, nitrile, alkyl, haloalkyl, aminoalkyl, cyanoalkyl, cycloalkyl and azacycloalkyl moieties; and a salt thereof.
12. The compound of claim 11 wherein R is selected from nitrile and aminoalkyl moieties.
13. The compound of claim 12 wherein R is a nitrile moiety, with a meta-relationship to each said pendent aminopyridine moiety.
14. The compound of claim 11 where said compound is an ammonium salt.
15. The compound of claim 14 wherein said salt has a counter ion that is a conjugate of a protic acid.
16. A method of inhibiting a nitric oxide synthase comprising contacting a nitric oxide synthase with an effective amount of a compound of a formula
or a salt thereof.
17. The method of claim 16 wherein R is selected from nitrile and aminoalkyl moieties.
18. The method of claim 16 wherein R is nitrile.
19. The method of claim 18 wherein R has a meta-relationship to each said pendent aminopyridine moiety.
20. The method of claim 17 selective for inhibition of neuronal nitric oxide synthase.