Format

Send to

Choose Destination
Bioorg Med Chem Lett. 2008 Jan 15;18(2):726-31. Epub 2007 Nov 19.

Optimization of biaryl Selective HDAC1&2 Inhibitors (SHI-1:2).

Author information

1
Department of Drug Design and Optimization-Medicinal Chemistry, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA. David_Witter@Merck.com

Abstract

A class of biaryl benzamides was identified and optimized as selective HDAC1&2 inhibitors (SHI-1:2). These agents exhibit selectivity over class II HDACs 4-7, as well as class I HDACs 3 and 8; providing examples of selective HDAC inhibitors for the HDAC isoforms most closely associated with cancer. The hypothesis for the increased selectivity is the binding of a pendant aromatic group in the internal cavity of the HDAC1&2 enzymes. SAR development based on an initial lead led to a series of potent and selective inhibitors with reduced off-target activity and tumor growth inhibition activity in a HCT-116 xenograft model.

PMID:
18060775
DOI:
10.1016/j.bmcl.2007.11.047
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center