Abstract
This review traces the origins of the chemical structure of the cyclooxygenase inhibitors celecoxib and rofecoxib. Early results from the search for non-steroid estrogens led to the triaryl-ethylenes such as chlortrianisene. A congener that incorporated a water-solubilizing basic ether grouping unexpectedly led to an estrogen antagonist and eventually the drug clomiphene. Elaboration of the structure gave the widely used drug used to treat breast cancer tamoxifen. Cyclized analogues such as nafoxidine showed equivalent activity but were not pursued. Later elaboration of those structures gave the now-marketed drug raloxifene. An indole analogue, indoxole, (2,3-dianisylindole) surprisingly showed anti-inflammatory activity. An analogue program designed to reduce photosensitivity from that compound eventually led to the discovery that the indole ring could be replaced by a simple thiazole, This resulted in the experimental cyclooxygenase inhibitor itazagrel. This compound incorporates many of the structural features found in celecoxib.
Keywords: cox-2 inhibitor, celecoxib, rofecoxib, chlortrianisene, clomiphene
Current Medicinal Chemistry
Title: Tracing the Origins of COX-2 Inhibitors Structures+
Volume: 9 Issue: 15
Author(s): Dan Lednicer
Affiliation:
Keywords: cox-2 inhibitor, celecoxib, rofecoxib, chlortrianisene, clomiphene
Abstract: This review traces the origins of the chemical structure of the cyclooxygenase inhibitors celecoxib and rofecoxib. Early results from the search for non-steroid estrogens led to the triaryl-ethylenes such as chlortrianisene. A congener that incorporated a water-solubilizing basic ether grouping unexpectedly led to an estrogen antagonist and eventually the drug clomiphene. Elaboration of the structure gave the widely used drug used to treat breast cancer tamoxifen. Cyclized analogues such as nafoxidine showed equivalent activity but were not pursued. Later elaboration of those structures gave the now-marketed drug raloxifene. An indole analogue, indoxole, (2,3-dianisylindole) surprisingly showed anti-inflammatory activity. An analogue program designed to reduce photosensitivity from that compound eventually led to the discovery that the indole ring could be replaced by a simple thiazole, This resulted in the experimental cyclooxygenase inhibitor itazagrel. This compound incorporates many of the structural features found in celecoxib.
Export Options
About this article
Cite this article as:
Lednicer Dan, Tracing the Origins of COX-2 Inhibitors Structures+, Current Medicinal Chemistry 2002; 9 (15) . https://dx.doi.org/10.2174/0929867023369727
DOI https://dx.doi.org/10.2174/0929867023369727 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- 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
-
Interactions of Vascular Endothelial Growth Factor and p53 with miR-195 in Thyroid Carcinoma: Possible Therapeutic Targets in Aggressive Thyroid Cancers
Current Cancer Drug Targets Lone Atrial Fibrillation- A Diagnosis of Exclusion
Current Pharmaceutical Design Focus on Ulcerative Colitis: Stable Gastric Pentadecapeptide BPC 157
Current Medicinal Chemistry From Na+/K+-ATPase and Cardiac Glycosides to Cytotoxicity and Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry Editorial [Hot topic: Natural Antioxidants and their Derivatives:Biology and Clinical Application (Guest Editors: Thea Magrone, Yoshio Kumazawa & Emilio Jirillo)]
Current Topics in Medicinal Chemistry Regulation of Hepatic Transporters by Xenobiotic Receptors
Current Drug Metabolism Synthesis of Mannich Bases by Two Different Methods and Evaluation of their Acetylcholine Esterase and Carbonic Anhydrase Inhibitory Activities
Letters in Drug Design & Discovery In Silico ADME Prediction: Data Sets and Models
Current Computer-Aided Drug Design Pidotimod and Immunological Activation in Individuals Infected with HIV
Current HIV Research Pleural Fluid Analysis for Evaluating Pleural Effusions
Current Respiratory Medicine Reviews Therapeutic Drugs that Behave as Mechanism-Based Inhibitors of Cytochrome P450 3A4
Current Drug Metabolism Sentinel Node Imaging
Current Medical Imaging New Analogues of Mycophenolic Acid
Mini-Reviews in Medicinal Chemistry PET Imaging of Multidrug Resistance in Tumors Using 18F-Fluoropaclitaxel
Current Topics in Medicinal Chemistry Meet Our Editorial Board Member
Current Cancer Drug Targets Anticancer Effects of Garlic and Garlic-derived Compounds for Breast Cancer Control
Anti-Cancer Agents in Medicinal Chemistry Vitamin D and Cystic Fibrosis Lung Disease
Mini-Reviews in Medicinal Chemistry Imidazoles and Benzimidazoles as Tubulin-Modulators for Anti-Cancer Therapy
Current Medicinal Chemistry Rapamycin-loaded Immunoliposomes Functionalized with Trastuzumab: A Strategy to Enhance Cytotoxicity to HER2-positive Breast Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Design, Sar, and Metabolism Study of Crucifereae Family Compound (Spirobrassinin) and its Analogs for Antiangiogenic Potential Targeting Hsp90
Current Proteomics