title: 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.
authors.affiliation: Norman Consulting , 18 Pink Lane, Burnham, Bucks, SL1 8JW , UK peter.norman2@btinternet.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Norman
mesh_terms: D000577:Amides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015195:Drug Design; D004335:Drug and Narcotic Control; D006801:Humans; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D010330:Patents as Topic; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D019141:Respiratory System Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: C436945:3-aminopyrazole; D000577:Amides; D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D019141:Respiratory System Agents; D053613:Janus Kinase 1