2,4-Diaminopyrimidine MK2 inhibitors. Part II: Structure-based inhibitor optimization.

Autor:	Harris CM; Abbott Laboratories, 100 Research Drive, Worcester, MA 01605-5314, USA., Ericsson AM, Argiriadi MA, Barberis C, Borhani DW, Burchat A, Calderwood DJ, Cunha GA, Dixon RW, Frank KE, Johnson EF, Kamens J, Kwak S, Li B, Mullen KD, Perron DC, Wang L, Wishart N, Wu X, Zhang X, Zmetra TR, Talanian RV
Jazyk:	angličtina
Zdroj:	Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2010 Jan 01; Vol. 20 (1), pp. 334-7. Date of Electronic Publication: 2009 Oct 29.
DOI:	10.1016/j.bmcl.2009.10.103
Abstrakt:	We describe structure-based optimization of a series of novel 2,4-diaminopyrimidine MK2 inhibitors. Co-crystal structures (see accompanying Letter) demonstrated a unique inhibitor binding mode. Resulting inhibitors had IC(50) values as low as 19nM and moderate selectivity against a kinase panel. Compounds 15, 31a, and 31b inhibit TNFalpha production in peripheral human monocytes. (Copyright 2009 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu Full Text from ScienceDirect