- The discovery of novel benzofuran-2-carboxylic acids as potent Pim-1 inhibitors.
The discovery of novel benzofuran-2-carboxylic acids as potent Pim-1 inhibitors.
Bioorganic & medicinal chemistry letters (2011-04-22)
Yibin Xiang, Bradford Hirth, Gary Asmussen, Hans-Peter Biemann, Kimberly A Bishop, Andrew Good, Maria Fitzgerald, Tatiana Gladysheva, Annuradha Jain, Katherine Jancsics, Jinyu Liu, Markus Metz, Andrew Papoulis, Renato Skerlj, J David Stepp, Ronnie R Wei
PMID21507633
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.
MATERIALS