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Bioorg Med Chem Lett. 2015 May 1;25(9):1842-8. doi: 10.1016/j.bmcl.2015.03.045. Epub 2015 Mar 24.

Development of methyl isoxazoleazepines as inhibitors of BET.

Author information

1
Constellation Pharmaceuticals, 215 First St., Suite 200, Cambridge, MA 02142, USA. Electronic address: mike.hewitt@constellationpharma.com.
2
Constellation Pharmaceuticals, 215 First St., Suite 200, Cambridge, MA 02142, USA.

Erratum in

  • Bioorg Med Chem Lett. 2015 Sep 1;25(17):3755. Jayaran, Hariharan [corrected to Jayaram, Hariharan].

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.

KEYWORDS:

BET inhibitors; Bromodomains; Isoxazoles; MYC; Unbound clearance

PMID:
25851940
DOI:
10.1016/j.bmcl.2015.03.045
[Indexed for MEDLINE]

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