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.