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Discovery of Potent and Selective Tricyclic Inhibitors of Bruton's Tyrosine Kinase with Improved Druglike Properties.

Authors :
Wang X
Barbosa J
Blomgren P
Bremer MC
Chen J
Crawford JJ
Deng W
Dong L
Eigenbrot C
Gallion S
Hau J
Hu H
Johnson AR
Katewa A
Kropf JE
Lee SH
Liu L
Lubach JW
Macaluso J
Maciejewski P
Mitchell SA
Ortwine DF
DiPaolo J
Reif K
Scheerens H
Schmitt A
Wong H
Xiong JM
Xu J
Zhao Z
Zhou F
Currie KS
Young WB
Source :
ACS medicinal chemistry letters [ACS Med Chem Lett] 2017 May 03; Vol. 8 (6), pp. 608-613. Date of Electronic Publication: 2017 May 03 (Print Publication: 2017).
Publication Year :
2017

Abstract

In our continued effort to discover and develop best-in-class Bruton's tyrosine kinase (Btk) inhibitors for the treatment of B-cell lymphomas, rheumatoid arthritis, and systemic lupus erythematosus, we devised a series of novel tricyclic compounds that improved upon the druglike properties of our previous chemical matter. Compounds exemplified by G-744 are highly potent, selective for Btk, metabolically stable, well tolerated, and efficacious in an animal model of arthritis.

Details

Language :
English
ISSN :
1948-5875
Volume :
8
Issue :
6
Database :
MEDLINE
Journal :
ACS medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
28626519
Full Text :
https://doi.org/10.1021/acsmedchemlett.7b00103