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.
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
J
J
Balzarini
W G
WG
Brouwer
E E
EE
Felauer
E
E
De Clercq
A
A
Karlsson
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