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Arzneimittelforschung 2002; 52(11): 833-839
DOI: 10.1055/s-0031-1299976
Antibiotics · Antiviral Drugs · Chemotherapeutics · Cytostatics
Editio Cantor Verlag Aulendorf (Germany)

Synthesis and Evaluation of Anti-HIV-1 and Anti-HSV-1 Activities of 4H-[1,2,4]-Triazolo [1,5-a]pyrimidin-5-one Derivatives

Atef A. Abdel-Hafez
a   Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Toyama, Japan
b   Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut, Egypt
,
Hosny A. H. Elsherief
c   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt
,
Michiko Jo
a   Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Toyama, Japan
,
Masahiko Kurokawa
d   School of Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Toyama, Japan
,
Kimiyasu Shiraki
d   School of Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Toyama, Japan
,
Takuya Kawahata
e   Osaka Prefectural Institute of Public Health, Osaka, Japan
,
Toru Otake
e   Osaka Prefectural Institute of Public Health, Osaka, Japan
,
Norio Nakamura
a   Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Toyama, Japan
,
Masao Hattori
a   Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Toyama, Japan
› Author Affiliations
Further Information

Publication History

Publication Date:
26 December 2011 (online)

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Summary

In a one pot procedure, 18 compounds of 7-(substituted phenyl)-2-substituted-6,7-dihydro-4H-[1,2,4]triazolo[1,5-a] pyrimidin-5-one derivatives (16–33) have been synthesized. 3(5)-Amino-5(3)-substi-tuted-1,2,4-triazole derivatives (7–12) were used as synthones which were cyclo-condensed by fusion with substituted methyl cinnamate esters (13–15) to afford the target compounds (16–33). In an effort to develop new non-nucleoside antiviral agents, compounds 16–33 were evaluated for their anti-HIV-1 and anti- HSV-1 activities. Complete inhibition of the proliferation of HIV-1 viruses was achieved by compounds 22, 23 and 24 at concentrations of 25, 25 and 50 µg/ml, respectively. 7-Phenyl-2-(n-pentyl)-6,7-dihy-dro-4H-[1,2,4]triazolo[1,5-a]pyrimidin-5-one (19) exhibited potential activity against HSV-I with 88 % reduction in the viral plaques. The suggested marked specificity of this class of compounds as anti-HIV-1 and HSV-1 agents is discussed.

Zusammenfassung

Synthese und Evaluierung der Anti-HIV-1- und Anti-HSV-1-Aktivität von 4H-[1,2,4]-Triazolo[1,5-a]pyrimidin-5-on-Derivativen

In einem einstufigen Verfahren wurden 18 Verbindungen von 7-(substituierten Phenyl)-2-substituierten-6,7-dihydro-4H-[1,2,4] triazolo[1,5-a]pyrimidin-5-on-Derivaten (16–33) synthetisiert. 3(5)-Amino-5(3)-subsituierte-1,2,4-triazol Derivate (7–12) wurden als Synthone verwendet, mittels derer durch Cyclokon-densation mit substituierten Methyl-Zimtsäureestern (13–15) die Zielstrukturen (16–33) entstanden. Um neue nicht-nucleosidische antivirale Wirkstoffe zu entwickeln, wurden die Verbindungen 16–33 auf ihre Anti-HIV-1- und Anti-HSV-1-Aktivität geprüft. Eine vollständige Hemmung des Wachstums der HIV-1-Viren wurde bei den Verbindungen 22–24 bei Konzentrationen von 25, 25 und 50 mg/ml erreicht. 7-Phenyl-2-(n-pentyl)-6,7-dihydro-4-[1,2,4]triazolo [1,5-a]pyri-midin-5-on 19 zeigte Aktivität gegen HSV-1 bei einer 88 % igen Verminderung der Viren. Die ausgeprägte Spezifität dieser Klasse von Verbindungen als Anti-HIV-1- und HSV-1-Wirkstoffe wird diskutiert.

Key words

Anti-HIV-1 agents - Anti-HSV-1 agents - Antiviral agents, non-nucleoside - 4H-[1,2,4]Triazolo-[1,5-a] pyrimidin-5-ones, antiviral activities, synthesis