Bioorg Med Chem Lett. 2010 Sep 1;20(17):5113-8. Epub 2010 Jul 13.

Discovery of imidazo[1,2-b]pyridazine derivatives as IKKbeta inhibitors. Part 1: Hit-to-lead study and structure-activity relationship.

Shimizu H, Tanaka S, Toki T, Yasumatsu I, Akimoto T, Morishita K, Yamasaki T, Yasukochi T, Iimura S.

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R&D Division, Daiichi Sankyo Co., Ltd, Edogawa-ku, Tokyo, Japan. shimizu.hiroki.hu@daiichisankyo.co.jp

Abstract

Imidazo[1,2-b]pyridazine derivatives from high-throughput screening were developed as IKKbeta inhibitors. By the optimization of the 3- and 6-position of imidazo[1,2-b]pyridazine scaffold, cell-free IKKbeta inhibitory activity and TNFalpha inhibitory activity in THP-1 cell increased. Also, these compounds showed high kinase selectivity. The structure-activity relationship was revealed and the interaction model of imidazo[1,2-b]pyridazine compounds with IKKbeta was constructed.

PMID:: 20675134; [PubMed - indexed for MEDLINE]

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