Discovery of BMS-955176, a Second Generation HIV-1 Maturation Inhibitor with Broad Spectrum Antiviral Activity

  • ACS Med Chem Lett. 2016 Apr 22;7(6):568-72. doi: 10.1021/acsmedchemlett.6b00010.
Alicia Regueiro-Ren  1 ,  Zheng Liu  1 ,  Yan Chen  1 ,  Ny Sin  1 ,  Sing-Yuen Sit  1 ,  Jacob J Swidorski  1 ,  Jie Chen  1 ,  Brian L Venables  1 ,  Juliang Zhu  1 ,  Beata Nowicka-Sans  1 ,  Tricia Protack  1 ,  Zeyu Lin  1 ,  Brian Terry  1 ,  Himadri Samanta  1 ,  Sharon Zhang  1 ,  Zhufang Li  1 ,  Brett R Beno  1 ,  Xiaohua S Huang  1 ,  Sandhya Rahematpura  1 ,  Dawn D Parker  1 ,  Roy Haskell  1 ,  Susan Jenkins  1 ,  Kenneth S Santone  1 ,  Mark I Cockett  1 ,  Mark Krystal  1 ,  Nicholas A Meanwell  1 ,  Umesh Hanumegowda  1 ,  Ira B Dicker  1
Affiliations
  • 1. Departments of Discovery Chemistry, Chemical Synthesis, Virology, Computer-Assisted Drug Design, and Pharmaceutical Candidate Optimization, B ristol-Myers Squibb Research and Development , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
PMID: 27326328 DOI: 10.1021/acsmedchemlett.6b00010
Abstract

HIV-1 maturation inhibition (MI) has been clinically validated as an approach to the control of HIV-1 Infection. However, identifying an MI with both broad polymorphic spectrum coverage and good oral exposure has been challenging. Herein, we describe the design, synthesis, and preclinical characterization of a potent, orally active, second generation HIV-1 MI, BMS-955176 (2), which is currently in Phase IIb clinical trials as part of a combination antiretroviral regimen.

Keywords
BMS-955176; HIV-1; antiviral; betulinic acid; maturation inhibitors; triterpene.