Activity of various thiocarboxanilide derivatives against wild-type and several mutant human immunodeficiency virus type 1 strains

Amino Acid Substitutions at Position 190 of Human Immunodeficiency Virus Type 1 Reverse Transcriptase Increase Susceptibility to Delavirdine and Impair Virus Replication

“…Previous studies have demonstrated that resistance to NNRTI drugs, specifically quinoxilanes, carboxanilides, and piperizines, is conferred by several amino acid substitutions at position 190 of HIV-1 RT (2,4,16,18,28). In these studies, drug-resistant viruses were selected in vitro by serial cultivation of HIV-1 in the presence of increasing drug concentrations.…”

Binding of the Second Generation Non-nucleoside Inhibitor S-1153 to HIV-1 Reverse Transcriptase Involves Extensive Main Chain Hydrogen Bonding

“…So-called "first generation" NNRTI drugs, such as nevirapine and delavirdine (U-90152), are generally very susceptible to the effects of single point resistance mutations within RT (6,7). In contrast, more recent "second generation" NNRTIs, such as efavirenz (DMP-266) (8), the carboxanlide, UC-781 (9), and certain quinoxalines (10), demonstrate much greater resilience to the presence of such mutations within RT.…”

Non-Nucleoside Reverse Transcriptase Inhibitors: The NNRTI Boom

“…UC 84 completely protected CEM-SS cells infected with HIV-1 from the cytopathic effect of HIV with an EC 50 value ranging from 0.1 µM to 1.0 µM, depending on the infectivity condition (Bader et al, 1991). UC 84 served as a lead (Balzarini et al, 1995) and consists of an oxathiin moiety (part a), a carboxamide group (part b) and a 2-chlorobenzoic acid (part c) that is esterified with an isopropyl group (part d) (Figure 13).…”