2-(2,6-Dihalophenyl)-3-(pyrimidin-2-yl)-1,3-thiazolidin-4-ones as non-nucleoside HIV-1 reverse transcriptase inhibitors

• Published in: Antiviral research Vol. 63; no. 2; pp. 79 - 84
• Main Authors: Rao, A, Balzarini, J, Carbone, A, Chimirri, A, De Clercq, E, Monforte, A.M, Monforte, P, Pannecouque, C, Zappalà, M
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.08.2004; Elsevier
• Subjects: 1,3-Thiazolidin-4-ones; Amino Acid Substitution; Anti-HIV activity; Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacology; Anti-HIV Agents - toxicity; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Drug Evaluation, Preclinical; Drug Resistance, Viral - genetics; HIV-1 - drug effects; HIV-1 - growth & development; Human immunodeficiency virus 1; Medical sciences; Molecular Structure; Mutation, Missense; NNRTIs; Pharmacology. Drug treatments; Pyrimidines - chemical synthesis; Pyrimidines - chemistry; Pyrimidines - pharmacology; Pyrimidines - toxicity; Reverse Transcriptase Inhibitors - chemical synthesis; Reverse Transcriptase Inhibitors - chemistry; Reverse Transcriptase Inhibitors - pharmacology; Reverse Transcriptase Inhibitors - toxicity; Structure-Activity Relationship; Thiazoles - chemical synthesis; Thiazoles - chemistry; Thiazoles - pharmacology; Thiazoles - toxicity; Virus Replication - drug effects; Anti-HIV activity; NNRTIs; 1,3-Thiazolidin-4-ones; Immunopathology; HIV-1 virus; Non nucleoside compound; Retroviridae; AIDS; Immune deficiency; Lentivirus; Infection; Virus; Viral disease; Reverse transcriptase inhibitor; Antiviral; Human immunodeficiency virus
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2004.03.004

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).