Discovery and optimization of novel constrained pyrrolopyridone BET family inhibitors.

Abstract:

:Novel conformationally constrained BET bromodomain inhibitors have been developed. These inhibitors were optimized in two similar, yet distinct chemical series, the 6-methyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-ones (A) and the 1-methyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-ones (B). Each series demonstrated excellent activity in binding and cellular assays, and lead compounds from each series demonstrated significant efficacy in in vivo tumor xenograft models.

journal_name

Bioorg Med Chem Lett

authors

Fidanze SD,Liu D,Mantei RA,Hasvold LA,Pratt JK,Sheppard GS,Wang L,Holms JH,Dai Y,Aguirre A,Bogdan A,Dietrich JD,Marjanovic J,Park CH,Hutchins CW,Lin X,Bui MH,Huang X,Wilcox D,Li L,Wang R,Kovar P,Magoc TJ,Raj

doi

10.1016/j.bmcl.2018.04.020

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

1804-1810

issue

10

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(18)30332-9

journal_volume

28

pub_type

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