Design and synthesis of carbazole carboxamides as promising inhibitors of Bruton’s tyrosine kinase (BTK) and Janus kinase 2 (JAK2)

• Published in: Bioorganic & medicinal chemistry letters 2015-10, Vol.25 (19), p.4265-4269
• Main Authors: Liu, Qingjie, Batt, Douglas G., Lippy, Jonathan S., Surti, Neha, Tebben, Andrew J., Muckelbauer, Jodi K., Chen, Lin, An, Yongmi, Chang, Chiehying, Pokross, Matt, Yang, Zheng, Wang, Haiqing, Burke, James R., Carter, Percy H., Tino, Joseph A.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Amides - chemical synthesis; Amides - chemistry; Amides - pharmacology; BASIC BIOLOGICAL SCIENCES; Bruton’s tyrosine kinase (BTK); Carbazole; Carbazoles - chemistry; Carbazoles - pharmacology; Dose-Response Relationship, Drug; Drug Design; Humans; Janus kinase 2 (JAK2); Janus Kinase 2 - antagonists & inhibitors; Janus Kinase 2 - metabolism; Molecular Structure; Protein Kinase Inhibitors - chemical synthesis; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacology; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - metabolism; Structure-Activity Relationship
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2015.07.102

[Display omitted] Four series of disubstituted carbazole-1-carboxamides were designed and synthesised as inhibitors of Bruton’s tyrosine kinase (BTK). 4,7- and 4,6-disubstituted carbazole-1-carboxamides were potent and selective inhibitors of BTK, while 3,7- and 3,6-disubstituted carbazole-1-carboxamides were potent and selective inhibitors of Janus kinase 2 (JAK2).