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Synthesis of Novel Derivatives of 4-Amino-3-(2-Furyl)-5-Mercapto-1,2,4-Triazole as Potential HIV-1 NNRTIs
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
* Author to whom correspondence should be addressed.
Received: 21 July 2007; in revised form: 17 August 2007 / Accepted: 20 August 2007 / Published: 22 August 2007
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 μM) and against HIV-1 reverse transcriptase (IC50 = 43.5 μM), which provided a good lead for further optimization.
Keywords: s-Triazole; Alkylation; Aminomethylation; Synthesis; HIV-1 NNRTIs
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Wu, J.; Liu, X.; Cheng, X.; Cao, Y.; Wang, D.; Li, Z.; Xu, W.; Pannecouque, C.; Witvrouw, M.; De Clercq, E. Synthesis of Novel Derivatives of 4-Amino-3-(2-Furyl)-5-Mercapto-1,2,4-Triazole as Potential HIV-1 NNRTIs. Molecules 2007, 12, 2003-2016.
Wu J, Liu X, Cheng X, Cao Y, Wang D, Li Z, Xu W, Pannecouque C, Witvrouw M, De Clercq E. Synthesis of Novel Derivatives of 4-Amino-3-(2-Furyl)-5-Mercapto-1,2,4-Triazole as Potential HIV-1 NNRTIs. Molecules. 2007; 12(8):2003-2016.
Wu, Jingde; Liu, Xinyong; Cheng, Xianchao; Cao, Yuan; Wang, Defeng; Li, Zhong; Xu, Wenfang; Pannecouque, Christophe; Witvrouw, Myriam; De Clercq, Erik. 2007. "Synthesis of Novel Derivatives of 4-Amino-3-(2-Furyl)-5-Mercapto-1,2,4-Triazole as Potential HIV-1 NNRTIs." Molecules 12, no. 8: 2003-2016.