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Bioorg Med Chem Lett. 2011 May 15;21(10):3050-6. doi: 10.1016/j.bmcl.2011.03.030. Epub 2011 Mar 16.

The discovery of novel benzofuran-2-carboxylic acids as potent Pim-1 inhibitors.

Author information

1
Department of Medicinal Chemistry, Drug and Biomaterial R&D, Genzyme Corp., 153 Second Avenue, Waltham, MA 02451, USA. yibin.xiang@genzyme.com

Abstract

Novel benzofuran-2-carboxylic acids, exemplified by 29, 38 and 39, have been discovered as potent Pim-1 inhibitors using fragment based screening followed by X-ray structure guided medicinal chemistry optimization. The compounds demonstrate potent inhibition against Pim-1 and Pim-2 in enzyme assays. Compound 29 has been tested in the Ambit 442 kinase panel and demonstrates good selectivity for the Pim kinase family. X-ray structures of the inhibitor/Pim-1 binding complex reveal important salt-bridge and hydrogen bond interactions mediated by the compound's carboxylic acid and amino groups.

PMID:
21507633
DOI:
10.1016/j.bmcl.2011.03.030
[Indexed for MEDLINE]

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