Abstract
Branched sugar nucleosides have attracted much attention due to their biological activities. We have demonstrated that epoxysugar nucleosides serve as versatile precursor for the stereo-defined synthesis of these nucleoside derivatives on the basis of its ring opening with organoaluminum or organosilicon reagents. In this review article, novel methods for the synthesis of nucleoside analogues branched at the 1' and 4'-position will be described. During this study, we could discover an anti-HIV agent, 4'-ethynylstavudine (Festinavir).
Festinavir showed more potent anti-HIV activity than the parent compound stavudine (d4T). Other significant properties of Festinavir are as follows: 1) much less toxic to various cells and also to mitochondorial DNA synthesis than d4T, 2) better substrate for human thymidine kinase than d4T, 3) resistant not only to chemical glycosidic bond cleavage but also to catabolism by thymidine phosphorylase, 4) the activity improves in the presence of a major mutation, K103N, associated with resistance to non-nucleoside reverse transcriptase inhibitors. Detailed profile of the antiviral activities, biology and pharmacology of Festinavir are also described.
Keywords: Epoxide, sugar, nucleoside, organoaluminum reagent, NRTIs, stavudine, anti-HIV-1 agent
Current Pharmaceutical Design
Title:From the Chemistry of Epoxy-Sugar Nucleosides to the Discovery of Anti-HIV Agent 4'-ethynylstavudine-Festinavir
Volume: 19 Issue: 10
Author(s): Kazuhiro Haraguchi, Shingo Takeda, Yutaka Kubota, Hiroki Kumamoto, Hiromichi Tanaka, Takayuki Hamasaki, Masanori Baba, Elijah Paintsil and Yung-Chi Cheng
Affiliation:
Keywords: Epoxide, sugar, nucleoside, organoaluminum reagent, NRTIs, stavudine, anti-HIV-1 agent
Abstract: Branched sugar nucleosides have attracted much attention due to their biological activities. We have demonstrated that epoxysugar nucleosides serve as versatile precursor for the stereo-defined synthesis of these nucleoside derivatives on the basis of its ring opening with organoaluminum or organosilicon reagents. In this review article, novel methods for the synthesis of nucleoside analogues branched at the 1' and 4'-position will be described. During this study, we could discover an anti-HIV agent, 4'-ethynylstavudine (Festinavir).
Festinavir showed more potent anti-HIV activity than the parent compound stavudine (d4T). Other significant properties of Festinavir are as follows: 1) much less toxic to various cells and also to mitochondorial DNA synthesis than d4T, 2) better substrate for human thymidine kinase than d4T, 3) resistant not only to chemical glycosidic bond cleavage but also to catabolism by thymidine phosphorylase, 4) the activity improves in the presence of a major mutation, K103N, associated with resistance to non-nucleoside reverse transcriptase inhibitors. Detailed profile of the antiviral activities, biology and pharmacology of Festinavir are also described.
Export Options
About this article
Cite this article as:
Haraguchi Kazuhiro, Takeda Shingo, Kubota Yutaka, Kumamoto Hiroki, Tanaka Hiromichi, Hamasaki Takayuki, Baba Masanori, Paintsil Elijah and Cheng Yung-Chi, From the Chemistry of Epoxy-Sugar Nucleosides to the Discovery of Anti-HIV Agent 4'-ethynylstavudine-Festinavir, Current Pharmaceutical Design 2013; 19 (10) . https://dx.doi.org/10.2174/1381612811319100011
DOI https://dx.doi.org/10.2174/1381612811319100011 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- 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
- Announcements
Related Articles
-
Advances in Oncolytic Virus Therapy for Glioma
Recent Patents on CNS Drug Discovery (Discontinued) The Misuse of Prescription Opioids: A Threat for Europe?
Current Drug Abuse Reviews How Recent Patents Have Changed our Clinical Approach in Cardio-Thoracic Surgery
Recent Patents on Regenerative Medicine Cancer Therapy: Targeting Mitochondria and other Sub-cellular Organelles
Current Pharmaceutical Design The Use of n-3 Polyunsaturated Fatty Acids as Therapeutic Agents for Inflammatory Diseases
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Renin-Angiotensin System in Central Nervous System Diseases and its Interaction with COVID-19
Current Medicinal Chemistry Clinical Implications of Recent Insights into the Structural Biology of Beta2 Adrenoceptors
Current Drug Targets Ω-3 Polyunsaturated Fatty Acids and Immune-Mediated Diseases: Inflammatory Bowel Disease and Rheumatoid Arthritis
Current Pharmaceutical Design Secondary Radiation-Induced Bone Tumours Demonstrate a High Degree of Genomic Instability Predictive of a Poor Prognosis
Current Genomics Prospects for Gene Therapy of Osteopetrosis
Current Gene Therapy VEGF, Angiopoietin-1 and -2 in Bronchial Asthma: New Molecular Targets in Airway Angiogenesis and Microvascular Remodeling
Recent Patents on Inflammation & Allergy Drug Discovery Defining and Managing Expectations for Early Immunotherapy Cancer Trials
Reviews on Recent Clinical Trials Gonioprobe, an Innovative Gamma-probe to Guide Parathyroid Radioguided Surgery: First Clinical Experiences with Navigator and Lock-ontarget Functions
Current Radiopharmaceuticals On the Diversity of Oxidative Bioactivation Reactions on Nitrogen- Containing Xenobiotics
Current Drug Metabolism Periostin as a Heterofunctional Regulator of Cardiac Development and Disease
Current Genomics Sirtuins: Novel Players in Male Reproductive Health
Current Medicinal Chemistry Deregulation of the Akt Pathway in Human Cancer
Current Cancer Drug Targets Application of dsRNA in Cancer Immunotherapy: Current Status and Future Trends
Anti-Cancer Agents in Medicinal Chemistry Synthesis and Applications of Bisheterocyclic Compounds
Current Organic Synthesis Nutritional Modulation of Terminal End Buds: Its Relevance to Breast Cancer Prevention
Current Cancer Drug Targets