Substituted diaminocarboxamide and diaminocarbonitrile pyrimidines, compositions thereof, and methods of treatment therewith

Patent metadata

Field	Value
Publication number	US-10266500-B2
Application number	US-201816021415-A
Country	US
Kind code	B2
Filing date	Jun 28, 2018
Priority date	Apr 22, 2011
Publication date	Apr 23, 2019
Grant date	Apr 23, 2019

Abstract

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.

First claim

What is claimed is:

1. A method for the treatment of interstitial pulmonary fibrosis, comprising administering to a subject having interstitial pulmonary fibrosis an effective amount of 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.

2. The method of claim 1 , wherein R 1 is an unsubstituted branched C 3-8 alkyl.

3. The method of claim 1 , wherein R 2 is a substituted cyclohexyl.

4. The method of claim 1 , wherein the compound is 4-((1R,3S)-3-hydroxycyclohexylamino)-2-(isopropylamino)pyrimidine-5-carboxamide.

5. The method of claim 1 , wherein the compound is 4-((1R,3S)-3-hydroxy-3-methylcyclohexylamino)-2-(isopropylamino)pyrimidine-5-carboxamide.

6. The method of claim 1 , wherein the compound is 4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)-2-(isopropylamino)pyrimidine-5-carboxamide.

7. The method of claim 1 , wherein the compound is 4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexyl amino)-2-(tert-pentylamino)pyrimidine-5-carboxamide.

8. The method of claim 1 , wherein the compound is 2-(tert-Butylamino)-4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide.

9. The method of claim 1 , wherein the compound is 4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)-2-(3-methylpentan-3-ylamino)pyrimidine-5-carboxamide.

10. The method of claim 1 , wherein the compound is 4-((1R,3S)-3-hydroxycyclohexylamino)-2-(tert-pentylamino)pyrimidine-5-carboxamide.

11. The method of claim 1 , wherein the compound is 2-(2,3-dimethylbutan-2-ylamino)-4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)pyrimidine-5-carboxamide.

12. The method of claim 1 , wherein the compound is 2-(sec-butylamino)-4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)pyrimidine-5-carboxamide.

13. The method 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.

14. The method of claim 1 , wherein the compound at a concentration of 10 μM inhibits JNK1 by at least about 50%.

Assignees

• Signal Pharm Llc

Inventors

• Bennett Brydon L
• Delgado Mercedes
• Elsner Jan
• Erdman Paul
• Hilgraf Robert
• Lebrun Laurie Ann
• Mccarrick Meg
• Nagy Mark A
• Norris Stephen
• Paisner David A
• Satoh Yoshitaka
• Sloss Marianne
• Tikhe Jayashree
• Yoon Won Hyung

Classifications

• C07D401/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D239/48 Primary

  Two nitrogen atoms · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P41/00

  Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution · CPC title

• A61P39/06

  Free radical scavengers or antioxidants · CPC title