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ID: ALA4184171

Journal: Bioorg Med Chem Lett

Title: Design and synthesis of a biaryl series as inhibitors for the bromodomains of CBP/P300.

Authors: Lai KW, Romero FA, Tsui V, Beresini MH, de Leon Boenig G, Bronner SM, Chen K, Chen Z, Choo EF, Crawford TD, Cyr P, Kaufman S, Li Y, Liao J, Liu W, Ly J, Murray J, Shen W, Wai J, Wang F, Zhu C, Zhu X, Magnuson S.

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.

CiteXplore: 29169673

DOI: 10.1016/j.bmcl.2017.11.025