Synthesis and in vitro activity of pyrrolo[3,4-d]pyrimidine-2,5-diones as potential non-nucleoside HCV inhibitors

Amany S. Mostafa, Serry A. El Bialy, Waleed A. Bayoumi, Youki Ueda, Masanori Ikeda, Nobuyuki Kato, Ali M. Abdelal

Research output: Contribution to journalArticle

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 μM) showed moderate anti-HCV activity; while compounds 9c, 9e and 9h showed weak activity.

Original languageEnglish
Pages (from-to)170-176
Number of pages7
JournalCurrent Enzyme Inhibition
Volume12
Issue number2
Publication statusPublished - Aug 1 2016

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Renilla Luciferases
Amines
Assays
Derivatives
Screening
Substitution reactions
pyrimidine
In Vitro Techniques

Keywords

  • HCV inhibitors
  • HuH-7-derived OR6 assay
  • Pyrrolo[3,4-d]pyrimidine
  • Renilla luciferase (RL) assay

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Drug Discovery

Cite this

Synthesis and in vitro activity of pyrrolo[3,4-d]pyrimidine-2,5-diones as potential non-nucleoside HCV inhibitors. / Mostafa, Amany S.; El Bialy, Serry A.; Bayoumi, Waleed A.; Ueda, Youki; Ikeda, Masanori; Kato, Nobuyuki; Abdelal, Ali M.

In: Current Enzyme Inhibition, Vol. 12, No. 2, 01.08.2016, p. 170-176.

Research output: Contribution to journalArticle

Mostafa, Amany S. ; El Bialy, Serry A. ; Bayoumi, Waleed A. ; Ueda, Youki ; Ikeda, Masanori ; Kato, Nobuyuki ; Abdelal, Ali M. / Synthesis and in vitro activity of pyrrolo[3,4-d]pyrimidine-2,5-diones as potential non-nucleoside HCV inhibitors. In: Current Enzyme Inhibition. 2016 ; Vol. 12, No. 2. pp. 170-176.
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