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ID: ALA1144533

Journal: Bioorg Med Chem

Title: Synthesis and evaluation of 2-{[2-(4-hydroxyphenyl)-ethyl]amino}pyrimidine-5-carboxamide derivatives as novel STAT6 inhibitors.

Authors: Nagashima S, Yokota M, Nakai E, Kuromitsu S, Ohga K, Takeuchi M, Tsukamoto S, Ohta M.

Abstract: The STAT6 (signal transducers and activators of transcription 6) protein is activated by interleukin (IL)-4 and IL-13, and plays an important role in T-helper cell 2 (Th2) differentiation. STAT6 might therefore be an excellent therapeutic target for various allergic conditions, including asthma and atopic diseases. We synthesized a series of 2-{[2-(4-hydroxyphenyl)ethyl]amino}pyrimidine-5-carboxamide derivatives and evaluated their STAT6 inhibitory activities. Among these compounds, 4-(benzylamino)-2-{[2-(3-chloro-4-hydroxyphenyl)ethyl]amino}pyrimidine-5-carboxamide (2t, AS1517499) showed potent STAT6 inhibition with an IC(50) value of 21 nM, and also inhibited IL-4-induced Th2 differentiation of mouse spleen T cells with an IC(50) value of 2.3 nM and without influencing T-helper cell 1 (Th1) differentiation induced by IL-12.

CiteXplore: 17071093

DOI: 10.1016/j.bmc.2006.10.015