Activity of various thiocarboxanilide derivatives against wild-type and several mutant human immunodeficiency virus type 1 strains.
A large variety of carboxanilide derivates in which the original oxathiin moiety present in the prototype compound UC84 was replaced by a non-cyclic lipophilic entity has been evaluated for their inhibitory effect against wild-type human immunodeficiency virus type 1 (HIV-1/IIIB) and several mutant viruses derived thereof (i.e. HIV-1/138-Lys, HIV-1/181-Cys, HIV-1/106-Ala and HIV-1/100-IIe). Isopropoxy was the most favorable substituent resulting in molecules that were markedly inhibitory to the wild-type (EC50 0.004-0.04 microgram/ml) as well as the mutant HIV-1 strains (EC50 0.06-0.75 microgram/ml). In this respect, they proved superior to several other HIV-1-specific non-nucleoside reverse transcriptase inhibitors (NNRTIs) that are currently the subject of clinical trials. One of the most potent HIV-1 inhibitors among the thiocarboxanilide derivatives, namely UC38, selected for a mutant virus strain in which Lys at position 101 and Gly at position 190 of the reverse transcriptase was replaced by Glu.
Balzarini
J
J
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Brouwer
W G
WG
Felauer
E E
EE
De Clercq
E
E
Karlsson
A
A
D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D001565:Benzoates / Q000737:chemistry / Q000494:pharmacology; D002261:Carboxin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D004352:Drug Resistance, Microbial; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D009154:Mutation; D012194:RNA-Directed DNA Polymerase / Q000187:drug effects; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000737:chemistry / Q000494:pharmacology
D000998:Antiviral Agents; D001565:Benzoates; C070134:NSC 615985; D018894:Reverse Transcriptase Inhibitors; D013859:Thiocarbamates; C083308:NSC 629243; D002261:Carboxin; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase