Evaluation of WO-2013040863, WO-2013041042 and WO-2013043962. Selective JAK1 inhibitors based on a 3-aminopyrazole-4-carboxamide scaffold

Abstract

1-alkyl-3-arylaminopyrazole-4-carboxamide derivatives have previously been described as JAK2 selective inhibitors. Modification of the 1-substituent to incorporate a 2-cyanoethyl moiety modulates the selectivity for JAK kinases providing JAK1 selective inhibitors. Three patent applications each claim different variations on this scaffold and provide highly potent JAK1 inhibitors, with up to 433-fold selectivity over JAK2. The inhibitors are claimed to be useful in the treatment of respiratory diseases, arthritis and cancer.

Keywords::

• asthma
• autoimmune disease
• JAK1 inhibitor
• rheumatoid arthritis

Declaration of interest

The author has received an honorarium from Informa for the preparation of this manuscript. There are no other conflicts of interest.