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.
Keywords: HCV inhibitors, HuH-7-derived OR6 assay, pyrrolo[3, 4-d]pyrimidine, Renilla Luciferase (RL) assay.
Current Enzyme Inhibition
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.
Export Options
About this article
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
DOI https://dx.doi.org/10.2174/1573408011666151013204142 |
Print ISSN 1573-4080 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6662 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Oxidised Products of Cholesterol: Their Role in Apoptosis
Current Nutrition & Food Science γ δ T Cell Modulation in Anticancer Treatment
Current Cancer Drug Targets Protein-based Strategies of Molecular Therapy in Allergy
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Advanced Neoplastic Disease as Immunologic, Endocrine and Metabolic Disorder
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry The Role of Obesity in Cardiomyopathy and Nephropathy
Current Pharmaceutical Design Inflamm-Aging, Cytokines and Aging: State of the Art, New Hypotheses on the Role of Mitochondria and New Perspectives from Systems Biology
Current Pharmaceutical Design Proteomic Analysis of the Kidney in Rat Biliary Cirrhosis
Current Proteomics Premature Ageing Prevention: Limitations and Perspectives of Pharmacological Interventions
Current Drug Targets Inflammatory and Vascular Alterations in Sepsis: The Role of Nitric Oxide- Dependent Mechanisms
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Biomarkers of Chronic Kidney Disease - Mineral and Bone Disorder (CKD-MBD), A Review of Published Patents and Patent Applications
Recent Patents on Biomarkers Clinical Profile of Relaxin, a Possible New Drug for Human Use
Current Drug Safety Role of Sirtuins and Calorie Restriction in Neuroprotection: Implications in Alzheimers and Parkinsons Diseases
Current Pharmaceutical Design Adjuvant Activity of Bursal Pentapeptide-(III-V) in Mice Immunized with the H9N2 Avian Influenza Vaccine
Protein & Peptide Letters Multidisciplinary Cancer Therapy with Telomerase-Specific Oncolytic Adenovirus
Current Cancer Therapy Reviews Recent Approaches for Studying the Role of Glia
CNS & Neurological Disorders - Drug Targets Inflammatory Bowel Disease and Celiac Disease: Overlaps in the Pathology and Genetics, and their Potential Drug Targets
Endocrine, Metabolic & Immune Disorders - Drug Targets Microarray Analysis Reveals CCL24/Eotaxin-2 as an Effector of the Pathogenetic Effects Induced by HIV-1 Nef
Current Drug Discovery Technologies Pathophysiology and Prevention of Bronchopulmonary Dysplasia
Current Pediatric Reviews IL28B Polymorphism, Blood Interferon-Alpha Concentration, and Disease Stage of HCV Mono-Infected and HCV-HIV Co-Infected Patients
Current HIV Research Chemogenomics and Parasitology: Small Molecules and Cell-Based Assays to Study Infectious Processes
Combinatorial Chemistry & High Throughput Screening