Methylpyrrole inhibitors of BET bromodomains.

Autor: Hasvold LA; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., Sheppard GS; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA. Electronic address: george.s.sheppard@abbvie.com., Wang L; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., Fidanze SD; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., Liu D; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., Pratt JK; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., Mantei RA; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., Wada CK; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., Hubbard R; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., Shen Y; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., Lin X; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., Huang X; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., Warder SE; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., Wilcox D; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., Li L; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., Buchanan FG; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., Smithee L; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., Albert DH; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., Magoc TJ; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., Park CH; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., Petros AM; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., Panchal SC; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., Sun C; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., Kovar P; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., Soni NB; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., Elmore SW; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., Kati WM; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA., McDaniel KF; AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2017 May 15; Vol. 27 (10), pp. 2225-2233. Date of Electronic Publication: 2017 Feb 24.
DOI: 10.1016/j.bmcl.2017.02.057
Abstrakt: An NMR fragment screen for binders to the bromodomains of BRD4 identified 2-methyl-3-ketopyrroles 1 and 2. Elaboration of these fragments guided by structure-based design provided lead molecules with significant activity in a mouse tumor model. Further modifications to the methylpyrrole core provided compounds with improved properties and enhanced activity in a mouse model of multiple myeloma.
(Copyright © 2017 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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