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

Alicia Regueiro-Ren; Zheng Liu; Yan Chen; Ny Sin; Sing-Yuen Sit; Jacob J Swidorski; Jie Chen; Brian L Venables; Juliang Zhu; Beata Nowicka-Sans; Tricia Protack; Zeyu Lin; Brian Terry; Himadri Samanta; Sharon Zhang; Zhufang Li; Brett R Beno; Xiaohua S Huang; Sandhya Rahematpura; Dawn D Parker; Roy Haskell; Susan Jenkins; Kenneth S Santone; Mark I Cockett; Mark Krystal; Nicholas A Meanwell; Umesh Hanumegowda; Ira B Dicker

doi:10.1021/acsmedchemlett.6b00010

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. eCollection 2016 Jun 9.

Authors

Alicia Regueiro-Ren¹, Zheng Liu¹, Yan Chen¹, Ny Sin¹, Sing-Yuen Sit¹, Jacob J Swidorski¹, Jie Chen¹, Brian L Venables¹, Juliang Zhu¹, Beata Nowicka-Sans¹, Tricia Protack¹, Zeyu Lin¹, Brian Terry¹, Himadri Samanta¹, Sharon Zhang¹, Zhufang Li¹, Brett R Beno¹, Xiaohua S Huang¹, Sandhya Rahematpura¹, Dawn D Parker¹, Roy Haskell¹, Susan Jenkins¹, Kenneth S Santone¹, Mark I Cockett¹, Mark Krystal¹, Nicholas A Meanwell¹, Umesh Hanumegowda¹, Ira B Dicker¹

Affiliation

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.

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.