Myosin light chain kinase inhibitor compounds, compositions and related methods of use

1. A compound of a formula

wherein R 3 is selected from H and alkyl moieties; R 4 is selected from H, alkyl, substituted alkyl, phenyl and substituted phenyl moieties; R 5 is selected from H and alkyl moieties; R 6 is selected from phenyl, substituted phenyl and halo moieties; and R 7 is selected from NHC(O)X and C(O)NHX, where X is (CH 2 ) m Y, and m is an integer selected from 0 to 3, and Y is selected from pyrrolidinyl, substituted and unsubstituted pyrrolyl, substituted and unsubstituted pyrazolyl, substituted and unsubstituted imidazolyl and substituted and unsubstituted cyclopentyl; and salts thereof.

2. The compound of claim 1 wherein R 7 is C(O)NHX, m is 2 and Y is selected from 5-membered carbocyclic and heterocyclic moieties.

3. The compound of claim 2 wherein Y is selected from pyrrolidinyl, substituted pyrrolidinyl, pyrrolyl, substituted pyrrolyl, pyrazolyl, substituted pyrazolyl, imidazolyl, substituted imidazolyl, cyclopentyl and substituted cyclopentyl moieties.

4. The compound of claim 1 wherein R 7 is C(O)NH(CH 2 ) m Y.

5. The compound of claim 4 wherein R 3 is hydrogen, R 6 is halo or phenyl, n is 10, m is 1 or 2, and Y is selected from 6-phenylpyridazin-3-yl, 1H-imidazol-2-yl methyl, 1-methylpyrrolidin-2-yl methyl, pyrrolidin-2-yl methyl and cyclopentyl methyl.

6. The compound according to claim 5 selected from the group consisting of

11-(6-imino-3-phenylpyridazin-1(6H)-yl)-N-((6-phenylpyridazin-3-yl)methyl)undecanamide;

11-(3-chloro-6-iminopyridazin-1(6H)-yl)-N-((6-phenylpyridazin-3-yl)methyl)undecanamide;

N-((1H-imidazol-2-yl)ethyl)-11-(6-imino-3-phenylpyridazin-1(6H)-yl)undecanamide;

11-(6-imino-3-phenylpyridazin-1(6H)-yl)-N-((1-methylpyrrolidin-2-yl)ethyl)undecanamide;

11-(6-imino-3-phenylpyridazin-1(6H)-yl)-N-(pyrrolidin-2-ylethyl)undecanamide; and

N-(cyclopentylethyl)-11-(6-imino-3-phenylpyridazin-1(6H)-yl)undecanamide.

7. The compound of claim 3 in a pharmaceutical composition.

8. The compound of claim 7 wherein said composition is formulated for one of oral, intraperitoneal and intravenous administration.

9. A method of inhibiting myosin light chain kinase activity, said method comprising:

providing a medium comprising a myosin light chain kinase; and

contacting said medium with a compound of a formula

wherein R 3 is selected from H and alkyl moieties; R 4 is selected from H, alkyl, substituted alkyl, phenyl and substituted phenyl moieties; R 5 is selected from H and alkyl moieties; R 6 is selected from phenyl, substituted phenyl and halo moieties; and R 7 is selected from NHC(O)X and C(O)NHX, where X is (CH 2 ) m Y, and m is an integer selected from 0 to 3, and Y is selected from pyrrolidinyl, substituted and unsubstituted pyrrolyl, substituted and unsubstituted pyrazolyl, substituted and unsubstituted imidazolyl and substituted and unsubstituted cyclopentyl; and salts thereof, said compound in an amount sufficient to at least partially inhibit said kinase activity.

10. The method of claim 9 wherein said contact is in vivo.

11. The method of claim 10 contacting at least one of epithelial and endothelial tissue exhibiting barrier dysfunction.

12. The method of claim 11 wherein the at least one of epithelial and endothelial tissue exhibiting barrier dysfunction that is contacted is injured pulmonary tissue.