Design and synthesis of a biaryl series as inhibitors for the bromodomains of CBP/P300 |
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| Authors: | Kwong Wah Lai F. Anthony Romero Vickie Tsui Maureen H. Beresini Gladys de Leon Boenig Sarah M. Bronner Kevin Chen Zhongguo Chen Edna F. Choo Terry D. Crawford Patrick Cyr Susan Kaufman Yingjie Li Jiangpeng Liao Wenfeng Liu Justin Ly Jeremy Murray Weichao Shen Steven Magnuson |
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| Affiliation: | 1. WuXi AppTec Co., Ltd., 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, People’s Republic of China;2. Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, United States |
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| Abstract: | A novel, potent, and orally bioavailable inhibitor of the bromodomain of CBP, compound 35 (GNE-207), has been identified through SAR investigations focused on optimizing al bicyclic heteroarene to replace the aniline present in the published GNE-272 series. Compound 35?has excellent CBP potency (CBP IC50?=?1?nM, MYC EC50?=?18?nM), a selectively index of?>2500-fold against BRD4(1), and exhibits a good pharmacokinetic profile. |
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| Keywords: | Bromodomain CBP inhibitor Volume of distribution Half-life |
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