Design and synthesis of novel pyrimidine analogs as highly selective, non-covalent BTK inhibitors. Issue 2 (15th January 2018)

• Record Type: Journal Article
• Authors: Kawahata, Wataru; Asami, Tokiko; Irie, Takayuki; Sawa, Masaaki
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 2(2018)
• Page Start: 145
• Page End: 151
• Publication Date: 2018-01-15
• Subjects: Bruton's tyrosine kinase -- Kinase inhibitor -- Kinase selectivity -- Pyrimidine -- Passive cutaneous anaphylaxis; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.11.037
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: BTK is a promising target for the treatment of multiple diseases such as B cell malignances, asthma, and rheumatoid arthritis. Here, we report the discovery of a series of novel pyrimidine analogs as potent, highly selective, non-covalent inhibitors of BTK. Compound25d demonstrated higher affinity to an unactivated conformation of BTK that resulted in an excellent kinase selectivity. Compound25d showed a good oral bioavailability in mice, and significantly inhibits the PCA reaction in mice.