Synthesis and structure–activity relationships of a novel series of pyrimidines as potent inhibitors of TBK1/IKKε kinases

…, E Smiljanic-Hurley, W Tsang, A Kamal, A Levy…

Index: McIver, Edward G.; Bryans, Justin; Birchall, Kristian; Chugh, Jasveen; Drake, Thomas; Lewis, Stephen J.; Osborne, Joanne; Smiljanic-Hurley, Ela; Tsang, William; Kamal, Ahmad; Levy, Alison; Newman, Michelle; Taylor, Debra; Arthur, J. Simon C.; Clark, Kristopher; Cohen, Philip Bioorganic and Medicinal Chemistry Letters, 2012 , vol. 22, # 23 p. 7169 - 7173,5

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Citation Number: 19

Abstract

The design, synthesis and structure–activity relationships of a novel series of 2, 4-diamino-5- cyclopropyl pyrimidines is described. Starting from BX795, originally reported to be a potent inhibitor of PDK1, we have developed compounds with improved selectivity and drug-like properties. These compounds have been evaluated in a range of cellular and in vivo assays, enabling us to probe the putative role of the TBK1/IKKε pathway in inflammatory diseases.