Synthesis and In Vitro Activity of Pyrrolo[3,4-d]pyrimidine-2,5-diones as Potential Non-nucleoside HCV Inhibitors

Title:Synthesis and In Vitro Activity of Pyrrolo[3,4-d]pyrimidine-2,5-diones as Potential Non-nucleoside HCV Inhibitors

Volume: 12 Issue: 2

Author(s): Amany S. Mostafa, Serry A. El Bialy, Waleed A. Bayoumi, Youki Ueda, Masanori Ikeda, Nobuyuki Kato and Ali M. Abdelal

Affiliation:

Keywords: HCV inhibitors, HuH-7-derived OR6 assay, pyrrolo[3, 4-d]pyrimidine, Renilla Luciferase (RL) assay.

Abstract: A new series of 1-methyl-4-phenyl-6-substituted-3,4,6,7-tetrahydro-1H-pyrrolo[3,4- d]pyrimidine-2,5-diones (9a-h) were investigated as potential non-nucleoside anti-HCV, through Renilla luciferase (RL) assay using HuH-7-derived OR6 assay system. The target derivatives 9a-h were synthesized in moderate to good yields through nucleophilic substitution, followed by subsequent cyclocondensation of the 6-bromomethyl dihydropyrimidine derivative 8 with the appropriate primary amine. Biological screening revealed that compound 9a (EC50 of 28 M) showed moderate anti-HCV activity; while compounds 9c, 9e and 9h showed weak activity.

Cite this article as:

Mostafa S. Amany, Bialy A. El Serry, Bayoumi A. Waleed, Ueda Youki, Ikeda Masanori, Kato Nobuyuki and Abdelal M. Ali, Synthesis and In Vitro Activity of Pyrrolo[3,4-d]pyrimidine-2,5-diones as Potential Non-nucleoside HCV Inhibitors, Current Enzyme Inhibition 2016; 12 (2) . https://dx.doi.org/10.2174/1573408011666151013204142