Format

Send to

Choose Destination
Bioorg Med Chem Lett. 2017 May 15;27(10):2225-2233. doi: 10.1016/j.bmcl.2017.02.057. Epub 2017 Feb 24.

Methylpyrrole inhibitors of BET bromodomains.

Author information

1
AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA.
2
AbbVie Inc., Oncology Discovery, 1 North Waukegan Rd., North Chicago, IL 60064, USA. Electronic address: george.s.sheppard@abbvie.com.

Abstract

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.

KEYWORDS:

BET proteins; Bromodomain; Fragment screening

PMID:
28268136
DOI:
10.1016/j.bmcl.2017.02.057
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center