6533b85bfe1ef96bd12bac24
RESEARCH PRODUCT
2-(2,6-Dihalophenyl)-3-(pyrimidin-2-yl)-1,3-thiazolidin-4-ones as non-nucleoside HIV-1 reverse transcriptase inhibitors.
Anna-maria MonforteJan BalzariniPietro MonforteAlba ChimirriMaria ZappalàA CarboneE. De ClercqChristophe PannecouqueA. Raosubject
NNRTI3-Thiazolidin-4-onesAnti-HIV activity13-Thiazolidin-4-oneNNRTIs; 1; 3-Thiazolidin-4-ones; anti-HIVAnti-HIV Agents1Drug Evaluation PreclinicalMutation MissenseBiologyVirus ReplicationVirusStructure-Activity RelationshipVirologyDrug Resistance ViralmedicineStructure–activity relationshipCytotoxicityPharmacologyReverse-transcriptase inhibitorMolecular Structurevirus diseasesanti-HIVSettore CHIM/08 - Chimica FarmaceuticaMolecular biologyIn vitroReverse transcriptaseThiazolesPyrimidinesViral replicationAmino Acid SubstitutionNNRTIsHIV-1Reverse Transcriptase InhibitorsNucleosidemedicine.drugdescription
Several 1,3-thiazolidin-4-ones bearing a 2,6-dihalophenyl group at C-2 and a substituted pyrimidin-2-yl ring at the N-3 were synthesised and evaluated as anti-HIV agents. The results of the in vitro tests showed that some of them were highly effective inhibitors of human immunodeficiency virus type-1 (HIV-1) replication at 10–40 nM concentrations with minimal cytotoxicity. Structure–activity relationship studies revealed that the nature of the substituents at the 2 and 3 positions of the thiazolidinone nucleus had a significant impact on the in vitro anti-HIV activity of this class of potent antiretroviral agents. The compounds had significantly reduced activity against the characteristic NNRTI-resistant virus mutants (bearing the K103N and Y181C RT mutations), thereby acting as non-nucleoside HIV-1 reverse transcriptase (RT) inhibitors (NNRTIs).
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2004-01-01 | Antiviral research |