Synthesis of Novel Derivatives of4-Amino-3-(2-Furyl)-5-Mercapto-1,2,4-Triazole asPotential HIV-1 NNRTIs

Molecules

Jingde Wu¹  Xinyong Liu¹  Xianchao Cheng¹  Yuan Cao¹  Defeng Wang¹  Zhong Li¹  Wenfang Xu¹  Christophe Pannecouque²  Myriam Witvrouw² 

[1] Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, No.44, Wenhuaxi Road, Jinan, 250012, P.R. China;Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium; E-mail:

关键词: s-Triazole;    Alkylation;    Aminomethylation;    Synthesis;    HIV-1 NNRTIs;   

DOI  :  10.3390/12082003

来源: mdpi

【 摘 要 】

A series of 5-alkylthio (2a-d), 4-arylideneamino (3a-d) and 4-arylideneamino-5-alkylthio derivatives (4a-f) of 4-amino-3-(2-furyl)-5-mercapto-1,2,4-triazole (1) were synthesized by alkylation of the parent compound with alkyl halides and condensation with aldehydes, respectively. Sulfanyl dimers 5a-d and 4-iminomethyl dimer 6 were correspondingly prepared by reaction with alkane dibromides and 1,4-diformylbenzene. Mannich base 7 was also synthesized by aminomethylation of the 3-sulfanyltriazole 1 at the N₁ position. The newly designed and synthesized substituted s-triazole derivatives were assayed for anti-HIV-1 activity by examination of their inhibition of HIV-1-induced cytopathogenicity in MT-4 cells and by determination of their inhibitory effect on HIV-1 reverse transcriptase. Compound 4e was found to be the most active inhibitor against HIV-1 replication in cell culture (EC₅₀ = 12 μM) and against HIV-1 reverse transcriptase (IC₅₀ = 43.5 μM), which provided a good lead for further optimization.

【 授权许可】

Unknown   
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