Development of methyl isoxazoleazepines as inhibitors of BET.

Abstract:

:In this report we detail the evolution of our previously reported thiophene isoxazole BET inhibitor chemotype exemplified by CPI-3 to a novel bromodomain selective chemotype (the methyl isoxazoleazepine chemotype) exemplified by carboxamide 23. The methyl isoxazoleazepine chemotype provides potent inhibition of the bromodomains of the BET family, excellent in vivo PK across species, low unbound clearance, and target engagement in a MYC PK-PD model.

journal_name

Bioorg Med Chem Lett

authors

Hewitt MC,Leblanc Y,Gehling VS,Vaswani RG,Côté A,Nasveschuk CG,Taylor AM,Harmange JC,Audia JE,Pardo E,Cummings R,Joshi S,Sandy P,Mertz JA,Sims RJ 3rd,Bergeron L,Bryant BM,Bellon S,Poy F,Jayaram H,Tang Y,Albrecht

doi

10.1016/j.bmcl.2015.03.045

subject

Has Abstract

pub_date

2015-05-01 00:00:00

pages

1842-8

issue

9

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(15)00251-6

journal_volume

25

pub_type

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