Novel Tricyclic Inhibitors of IκB Kinase
- 6 March 2009
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 52 (7) , 1994-2005
- https://doi.org/10.1021/jm8015816
Abstract
The design and synthesis of a novel series of oxazole-, thiazole-, and imidazole-based inhibitors of IkappaB 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.Keywords
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