☆ 4.7 Article

Novel Tricyclic Inhibitors of IκB Kinase

JOURNAL OF MEDICINAL CHEMISTRY (2009)

Journal

JOURNAL OF MEDICINAL CHEMISTRY

Volume 52, Issue 7, Pages 1994-2005

Publisher

AMER CHEMICAL SOC

DOI: 10.1021/jm8015816

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Chemistry, Medicinal

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Abstract

The design and synthesis of a novel series of oxazole-, thiazole-, and imidazole-based inhibitors of I kappa B kinase (IKK) are reported. Biological activity was improved compared to the pyrazolopurine lead, and the expedient synthesis of the new tricyclic systems allowed for efficient exploration of structure-activity relationships. This, combined with an iterative rat cassette dosing strategy, was used to identify compounds with improved pharmacokinetic (PK) profiles to advance for in vivo evaluation.

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