Synthesis And Anti-HIV-1Activities Of2-(N-Arylsulfonyllindol-3-Yl)-3-Aryl-l,3-Thi Azolidin-4-Ones

Acquired immune deficiency syndrome (AIDS) is caused by the humanimmunodeficiency virus (HIV) which has strong infectivity, resulting in loss of lymphocytefunction, serious damage to lymphoid tissue, decreasing immune function and even thecollapse of immune system. In the past two decades, twenty-five drugs, including nucleosideviral reverse transcriptase (R^T) inhibitors, non-nucleoside R^T inhibitors, protease inhibitors,integrase inhibitor and fusion (or entry) inhibitors, were approved for clinical use in the world.However, these drugs have only limited clinical benefit because of their side effects and theemergence of viral variants resistant to HIV-1inhibitors. Now, the study on the new and safeHIV-1inhibitors is still important for medical research.In this paper, twenty-one2-(N-arylsulfonylindol-3-yl)-3-aryl-1,3-thiazolidin-4-ones weresynthesized and preliminarily evaluated as HIV-1inhibitors in vitro. Their structures wereconfirmed by1H NMR^, EI-MS and IR^. Among all compounds, compounds4n and4pdisplayed the potent anti-HIV-1activities with EC₅₀values of3.48and8.61μg/mL, and TIvalues of34.08and>23.22, respectively.The structure-activity relationships (SAR^s) demonstrated that introduction of R²as4-Cland R³as H or3-Cl could afford the more promising and potent compounds. When R²and R³were H, the compound containing R¹as6-Me was less potent than that having R¹as H; whileR²as3-NO2and R³as4-Me, the compound with R¹as6-Me was more potent than thathaving R¹as H. Additionally, introduction of R²as4-Cl could afford the potent compounds.When the chlorine atom of the substituent R²of4n was substituted by the bromine atom togive4u, the anti-HIV-1activity of4u was reduced sharply. It suggested that the introductionof the chlorine atom at4-postion on the arylsulfonyl ring was important for the anti-HIV-1activity.