Novel tricyclic inhibitors of IkappaB kinase.


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Kempson, J; Spergel, SH; Guo, J; Quesnelle, C; Gill, P; Belanger, D; Dyckman, AJ; Li, T; Watterson, SH; Langevine, CM; Das, J; Moquin, RV; Furch, JA; Marinier, A; Dodier, M; Martel, A; Nirschl, D; Van Kirk, K; Burke, JR; Pattoli, MA; Gillooly, K; McIntyre, KW; Chen, L; Yang, Z; Marathe, PH; Wang-Iverson, D; Dodd, JH; McKinnon, M; Barrish, JC; Pitts, WJ

Published Date

  • April 9, 2009

Published In

Volume / Issue

  • 52 / 7

Start / End Page

  • 1994 - 2005

PubMed ID

  • 19267461

Pubmed Central ID

  • 19267461

Electronic International Standard Serial Number (EISSN)

  • 1520-4804

Digital Object Identifier (DOI)

  • 10.1021/jm8015816


  • eng

Conference Location

  • United States