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 Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
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,Albrechtdoi
10.1016/j.bmcl.2015.03.045subject
Has Abstractpub_date
2015-05-01 00:00:00pages
1842-8issue
9eissn
0960-894Xissn
1464-3405pii
S0960-894X(15)00251-6journal_volume
25pub_type
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