Inhibitors of HIV-1 attachment. Part 10. The discovery and structure-activity relationships of 4-azaindole cores

  • Bioorg Med Chem Lett. 2013 Jan 1;23(1):213-7. doi: 10.1016/j.bmcl.2012.10.120.
Tao Wang  1 ,  Zhong Yang ,  Zhongxing Zhang ,  Yi-Fei Gong ,  Keith A Riccardi ,  Pin-Fang Lin ,  Dawn D Parker ,  Sandhya Rahematpura ,  Marina Mathew ,  Ming Zheng ,  Nicholas A Meanwell ,  John F Kadow ,  John A Bender
Affiliations
  • 1. Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.
PMID: 23200254 DOI: 10.1016/j.bmcl.2012.10.120
Abstract

A series of 4-azaindole oxoacetic acid piperazine benzamides was synthesized and evaluated in an effort to identify an oral HIV-1 attachment inhibitor with the potential to improve upon the pre-clinical profile of BMS-378806 (7), an initial clinical compound. Modifications at the 7-position of the 4-azaindole core modulated potency significantly and SAR showed that certain compounds with a 5-membered ring heteroaryl group at that position were the most potent. Four of the compounds with the best profiles were evaluated in a rat pharmacokinetic model and all had superior oral bioavailability and lower clearance when compared with 7.