gsk1265744 and HIV-Infections

Although a relatively wide range of therapeutic options is currently available for the treatment of HIV/AIDS, it is still among the most serious and virulent diseases and is associated with a high mortality rate. Integrase strand transfer inhibitors (INSTIs), e.g., FDA-approved dolutegravir (DTG), bictegravir (BIC) and cabotegravir (CAB), have recently been included in standard highly active antiretroviral therapy (HAART) schemes as one of the five major components responsible for the most beneficial clinical outcome. In this paper, we describe a combinatorial amide synthesis, biological evaluation and in silico modeling of new INSTIs containing heteroaromatic bioisosteric substitution instead of the well-studied halogen-substituted benzyl fragment. With the focus on the mentioned diversity point, a medium-sized library of compounds was selected for synthesis. A biological study revealed that many molecules were highly active INSTIs (EC

Topics: Animals; Computer Simulation; HIV Infections; HIV Integrase; HIV Integrase Inhibitors; HIV-1; Humans; Male; Models, Molecular; Molecular Docking Simulation; Mutation; Oxazoles; Pyridones; Rats; Rats, Sprague-Dawley; Virus Replication