title: Synthesis of novel derivatives of 4-amino-3-(2-furyl)-5-mercapto-1,2,4-triazole as potential HIV-1 NNRTIs.
abstract: 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 microM) and against HIV-1 reverse transcriptase (IC50 = 43.5 microM), which provided a good lead for further optimization.
authors.affiliation: Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, No.44, Wenhuaxi Road, Jinan, 250012, PR China.
authors.forename: Jingde
authors.initials: J
authors.lastname: Wu
authors.forename: Xinyong
authors.initials: X
authors.lastname: Liu
authors.forename: Xianchao
authors.initials: X
authors.lastname: Cheng
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cao
authors.forename: Defeng
authors.initials: D
authors.lastname: Wang
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xu
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.forename: Myriam
authors.initials: M
authors.lastname: Witvrouw
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: C524607:4-amino-3-(2-furyl)-5-mercapto-1,2,4-triazole; D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D013438:Sulfhydryl Compounds; D014230:Triazoles