Substituted diaminocarboxamide and diaminocarbonitrile pyrimidines, compositions thereof, and methods of treatment therewith
Provided herein are Diaminopyrimidine Compounds having the following structures: wherein R 1 , R 2 , R 3 , and R 4 are as defined herein, compositions comprising an effective amount of a Diaminopyrimidine Compound, and methods for treating or preventing liver fibrotic disorders or a condition treatable or preventable by inhibition of a JNK pathway.
1. A compound of formula (I):
or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof,
wherein:
R 1 is substituted or unsubstituted branched C 3-8 alkyl; and
R 2 is substituted or unsubstituted cyclohexyl,
wherein the compound at a concentration of 10 μM inhibits JNK1 by at least about 50%.
2. The compound of claim 1 , wherein R 1 is an unsubstituted branched C 3-8 alkyl.
3. The compound of claim 1 , wherein R 2 is a substituted cyclohexyl.
4. A compound of formula (TB):
or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof,
wherein:
R 3 is substituted or unsubstituted branched C 3-8 alkyl; and
R 4 is substituted or unsubstituted cyclohexyl.
5. The compound of claim 4 , wherein R 4 is a substituted cyclohexyl.
6. A pharmaceutical composition comprising an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, and a pharmaceutically acceptable carrier, excipient or vehicle.
7. The compound of claim 1 , wherein the compound is 4-((1R,3S)-3-hydroxycyclohexylamino)-2-(isopropylamino)pyrimidine-5-carboxamide.
8. The compound of claim 1 , wherein the compound is 4-((1R,3S)-3-hydroxy-3-methylcyclohexylamino)-2-(isopropylamino)pyrimidine-5-carboxamide.
9. The compound of claim 1 , wherein the compound is 4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)-2-(isopropylamino)pyrimidine-5-carboxamide.
10. The compound of claim 1 , wherein the compound is 4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)-2-(tert-pentylamino)pyrimidine-5-carboxamide.
11. The compound of claim 1 , wherein the compound is 2-(tert-Butylamino)-4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide.
12. The compound of claim 1 , wherein the compound is 4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)-2-(3-methylpentan-3-ylamino)pyrimidine-5-carboxamide.
13. The compound of claim 1 , wherein the compound is 4-((1R,3S)-3-hydroxycyclohexylamino)-2-(tert-pentylamino)pyrimidine-5-carboxamide.
14. The compound of claim 1 , wherein the compound is 2-(2,3-dimethylbutan-2-ylamino)-4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)pyrimidine-5-carboxamide.
15. The compound of claim 1 , wherein the compound is 2-(sec-butylamino)-4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)pyrimidine-5-carboxamide.
16. The compound of claim 1 , wherein the compound is 2-((R)-3,3-dimethylbutan-2-ylamino)-4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)pyrimidine-5-carboxamide.
17. The compound of claim 4 , wherein the compound at a concentration of 10 μM inhibits JNK1 by at least about 50%.
18. A pharmaceutical composition comprising an effective amount of a compound of claim 4 , or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, and a pharmaceutically acceptable carrier, excipient or vehicle.