Design and synthesis of a biaryl series as inhibitors for the bromodomains of CBP/P300. Issue 1 (1st January 2018)

• Record Type: Journal Article
• Authors: Lai, Kwong Wah; Romero, F. Anthony; Tsui, Vickie; Beresini, Maureen H.; de Leon Boenig, Gladys; Bronner, Sarah M.; Chen, Kevin; Chen, Zhongguo; Choo, Edna F.; Crawford, Terry D.; Cyr, Patrick; Kaufman, Susan; Li, Yingjie; Liao, Jiangpeng; Liu, Wenfeng; Ly, Justin; Murray, Jeremy; Shen, Weichao; Wai, John; Wang, Fei; Zhu, Caicai; Zhu, Xiaoyu; Magnuson, Steven
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 1(2018)
• Page Start: 15
• Page End: 23
• Publication Date: 2018-01-01
• Subjects: Bromodomain -- CBP inhibitor -- Volume of distribution -- Half-life; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.11.025
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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.