| Structural highlights
Publication Abstract from PubMed
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.
The discovery of novel benzofuran-2-carboxylic acids as potent Pim-1 inhibitors.,Xiang Y, Hirth B, Asmussen G, Biemann HP, Bishop KA, Good A, Fitzgerald M, Gladysheva T, Jain A, Jancsics K, Liu J, Metz M, Papoulis A, Skerlj R, Stepp JD, Wei RR Bioorg Med Chem Lett. 2011 May 15;21(10):3050-6. Epub 2011 Mar 16. PMID:21507633[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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References
- ↑ Xiang Y, Hirth B, Asmussen G, Biemann HP, Bishop KA, Good A, Fitzgerald M, Gladysheva T, Jain A, Jancsics K, Liu J, Metz M, Papoulis A, Skerlj R, Stepp JD, Wei RR. The discovery of novel benzofuran-2-carboxylic acids as potent Pim-1 inhibitors. Bioorg Med Chem Lett. 2011 May 15;21(10):3050-6. Epub 2011 Mar 16. PMID:21507633 doi:10.1016/j.bmcl.2011.03.030
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