Synthesis and biological evaluation of 4-amino derivatives of benzimidazoquinoxaline, benzimidazoquinoline, and benzopyrazoloquinazoline as potent IKK inhibitors

  • Bioorg Med Chem Lett. 2007 Mar 1;17(5):1233-7. doi: 10.1016/j.bmcl.2006.12.017.
Francis Beaulieu  1 ,  Carl Ouellet ,  Edward H Ruediger ,  Makonen Belema ,  Yuping Qiu ,  Xuejie Yang ,  Jacques Banville ,  James R Burke ,  Kurt R Gregor ,  John F MacMaster ,  Alain Martel ,  Kim W McIntyre ,  Mark A Pattoli ,  F Christopher Zusi ,  Dolatrai Vyas
Affiliations
  • 1. Bristol-Myers Squibb Pharmaceutical Research Institute, 100 boul. de l'Industrie, Candiac, Que., Canada J5R 1J1. [email protected]
PMID: 17197177 DOI: 10.1016/j.bmcl.2006.12.017
Abstract

We have recently identified BMS-345541 (1) as a highly selective and potent inhibitor of IKK-2 (IC50 = 0.30 microM), which however was considerably less potent against IKK-1 (IC50 = 4.0 microM). In order to further explore the SAR around the imidazoquinoxaline tricyclic structure of 1, we prepared a series of tetracyclic analogues (7, 13, and 18). The synthesis and biological activities of these potent IKK inhibitors are described.