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

doi:10.2174/1573408011666151013204142

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 journal › Article › peer-review

1 Citation (Scopus)

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 language	English
Pages (from-to)	170-176
Number of pages	7
Journal	Current Enzyme Inhibition
Volume	12
Issue number	2
DOIs	https://doi.org/10.2174/1573408011666151013204142
Publication status	Published - Aug 1 2016

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

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10.2174/1573408011666151013204142

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

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.",

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

author = "Mostafa, {Amany S.} and {El Bialy}, {Serry A.} and Bayoumi, {Waleed A.} and Youki Ueda and Masanori Ikeda and Nobuyuki Kato and Abdelal, {Ali M.}",

year = "2016",

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doi = "10.2174/1573408011666151013204142",

language = "English",

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journal = "Current Enzyme Inhibition",

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T1 - Synthesis and in vitro activity of pyrrolo[3,4-d]pyrimidine-2,5-diones as potential non-nucleoside HCV inhibitors

AU - Mostafa, Amany S.

AU - El Bialy, Serry A.

AU - Bayoumi, Waleed A.

AU - Ueda, Youki

AU - Ikeda, Masanori

AU - Kato, Nobuyuki

AU - Abdelal, Ali M.

PY - 2016/8/1

Y1 - 2016/8/1

N2 - 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.

AB - 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.

KW - HCV inhibitors

KW - HuH-7-derived OR6 assay

KW - Pyrrolo[3,4-d]pyrimidine

KW - Renilla luciferase (RL) assay

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JO - Current Enzyme Inhibition

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IS - 2

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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