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Bioorg Med Chem Lett. 2009 Feb 1;19(3):644-9. doi: 10.1016/j.bmcl.2008.12.048. Epub 2008 Dec 24.

SAR and biological evaluation of analogues of a small molecule histone deacetylase inhibitor N-(2-aminophenyl)-4-((4-(pyridin-3-yl)pyrimidin-2-ylamino)methyl)benzamide (MGCD0103).

Author information

1
MethylGene Inc., Department of Medicinal Chemistry, 7220 Frederick-Banting, Montréal, Que., Canada H4S 2A1. raeppels@methylgene.com

Abstract

Analogues of the clinical compound MGCD0103 (A) were designed and synthesized. These compounds inhibit recombinant human HDAC1 with IC(50) values in the sub-micromolar range. In human cancer cells growing in culture these compounds induce hyperacetylation of histones, cause expression of the tumor suppressor protein p21(WAF1/CIP1), and inhibit cellular proliferation. Lead molecule of the series, compound 25 is metabolically stable, possesses favorable pharmacokinetic characteristics and is orally active in vivo in different mouse tumor xenograft models.

PMID:
19114304
DOI:
10.1016/j.bmcl.2008.12.048
[Indexed for MEDLINE]

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