1202902-07-5Relevant academic research and scientific papers
HIV-1 protease inhibitors with a transition-state mimic comprising a tertiary alcohol: Improved antiviral activity in cells
Mahalingam,Axelsson, Linda,Ekegren, Jenny K.,Wannberg, Johan,Kihlstr?m, Jacob,Unge, Torsten,Wallberg, Hans,Samuelsson, Bertil,Larhed, Mats,Hallberg, Anders
supporting information; experimental part, p. 607 - 615 (2010/07/06)
By a small modification in the core structure of the previously reported series of HIV-1 protease inhibitors that encompasses a tertiary alcohol as part of the transition-state mimicking scaffold, up to 56 times more potent compounds were obtained exhibiting EC50 values down to 3 nM. Three of the inhibitors also displayed excellent activity against selected resistant isolates of HIV-1. The synthesis of 25 new and optically pure HIV-1 protease inhibitors is reported, along with methods for elongation of the inhibitor P1′ side chain using microwave-accelerated, palladium-catalyzed cross-coupling reactions, the biological evaluation, and X-ray data obtained from one of the most potent analogues cocrystallized with both the wild type and the L63P, V82T, I84 V mutant of the HIV-1 protease.
