Design and synthesis of novel pyrimidine analogs as highly selective,non-covalent BTK inhibitors |
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Authors: | Wataru Kawahata Tokiko Asami Takayuki Irie Masaaki Sawa |
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Affiliation: | Research and Development, Carna Biosciences, Inc., 3rd Floor, BMA, 1-5-5 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan |
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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. Compound 25d demonstrated higher affinity to an unactivated conformation of BTK that resulted in an excellent kinase selectivity. Compound 25d showed a good oral bioavailability in mice, and significantly inhibits the PCA reaction in mice. |
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Keywords: | Bruton’s tyrosine kinase Kinase inhibitor Kinase selectivity Pyrimidine Passive cutaneous anaphylaxis |
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