Rao A, Balzarini J, Carbone A, Chimirri A, De Clercq E, Monforte A M, Monforte P, Pannecouque C, Zappalà M
Dipartimento Farmaco-Chimico, Università di Messina, viale Annunziata 98168 Messina, Italy.
Antiviral Res. 2004 Aug;63(2):79-84. 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).
合成了几种在C-2位带有2,6-二卤代苯基且在N-3位带有取代嘧啶-2-基环的1,3-噻唑烷-4-酮，并将其作为抗HIV药物进行评估。体外试验结果表明，其中一些化合物在10 - 40 nM浓度下是人类免疫缺陷病毒1型（HIV-1）复制的高效抑制剂，且细胞毒性极小。构效关系研究表明，噻唑烷酮核2位和3位取代基的性质对这类强效抗逆转录病毒药物的体外抗HIV活性有显著影响。这些化合物对具有特征性NNRTI抗性的病毒突变体（携带K103N和Y181C RT突变）的活性显著降低，从而作为非核苷类HIV-1逆转录酶（RT）抑制剂（NNRTIs）发挥作用。
