Abstract
This review covers recent progress in the discovery of selective glucocorticoid receptor (GR) antagonists. Potential therapeutic applications of selective GR antagonists are described including the pharmacological rationale and, in some cases, clinical evidence that underlies these proposed uses. Disease areas that are discussed are Cushings syndrome, psychotic depression, diabetes, obesity, Alzheimers disease, neuropathic pain, drug abuse, and glaucoma. Methods for evaluating GR antagonist properties (binding, functional, and in vivo assays) are briefly covered. Early research on steroidal ligands which led to the identification of the non-selective GR antagonist RU-486 (mifepristone) and the GR-selective steroid RU-43044 is reviewed as is subsequent work on related steroidal compounds. Structure activity relationships (SAR) of nonsteroidal GR antagonists from the following structural classes are presented: octahydrophenanthrenes, spirocyclic dihydropyridines, triphenylmethanes and diaryl ethers, chromenes, dibenzyl anilines, dihydroisoquinolines, pyrimidinediones, azadecalins, and aryl pyrazolo azadecalins.
Keywords: Glucocorticoid receptor antagonist, GR antagonist, nuclear receptor, mifepristone
Current Topics in Medicinal Chemistry
Title: Glucocorticoid Receptor Antagonists
Volume: 8 Issue: 9
Author(s): Robin D. Clark
Affiliation:
Keywords: Glucocorticoid receptor antagonist, GR antagonist, nuclear receptor, mifepristone
Abstract: This review covers recent progress in the discovery of selective glucocorticoid receptor (GR) antagonists. Potential therapeutic applications of selective GR antagonists are described including the pharmacological rationale and, in some cases, clinical evidence that underlies these proposed uses. Disease areas that are discussed are Cushings syndrome, psychotic depression, diabetes, obesity, Alzheimers disease, neuropathic pain, drug abuse, and glaucoma. Methods for evaluating GR antagonist properties (binding, functional, and in vivo assays) are briefly covered. Early research on steroidal ligands which led to the identification of the non-selective GR antagonist RU-486 (mifepristone) and the GR-selective steroid RU-43044 is reviewed as is subsequent work on related steroidal compounds. Structure activity relationships (SAR) of nonsteroidal GR antagonists from the following structural classes are presented: octahydrophenanthrenes, spirocyclic dihydropyridines, triphenylmethanes and diaryl ethers, chromenes, dibenzyl anilines, dihydroisoquinolines, pyrimidinediones, azadecalins, and aryl pyrazolo azadecalins.
Export Options
About this article
Cite this article as:
Clark D. Robin, Glucocorticoid Receptor Antagonists, Current Topics in Medicinal Chemistry 2008; 8 (9) . https://dx.doi.org/10.2174/156802608784535011
DOI https://dx.doi.org/10.2174/156802608784535011 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Heart Failure in Minority Populations - Impediments to Optimal Treatment in Australian Aborigines
Current Cardiology Reviews Classical Inhibitors of NOX NAD(P)H Oxidases Are Not Specific
Current Drug Metabolism Ivabradine: The Hope for a Good Treatment of Ischemic Heart Disease
Current Medicinal Chemistry Bcl-2 Proteins: Targets and Tools for Chemosensitisation of Tumor Cells
Current Medicinal Chemistry - Anti-Cancer Agents Synthesis and Applications of Bisheterocyclic Compounds
Current Organic Synthesis Saltatory and Sinusoidal Fetal Heart Rate (FHR) Patterns and significance of FHR ‘Overshoots’
Current Women`s Health Reviews Therapeutic Modulation of Glutamate Receptors in Major Depressive Disorder
Current Neuropharmacology Dose Related Patterns of Ventricular Arrhythmia due to Carvedilol Withdrawal in Patients with Systolic Heart Failure
Current Drug Safety Vascular Adenosine Receptors; Potential Clinical Applications
Current Vascular Pharmacology Isolated Perioperative Hypertension: Clinical Implications & Contemporary Treatment Strategies
Current Hypertension Reviews In-hospital Falls in Older Patients: The Risk Factors and The Role of Hyponatraemia
Current Aging Science Vicious Cycles Within the Neuropathophysiologic Mechanisms of Alzheimers Disease
Current Alzheimer Research Review of Topiramate: An Antiepileptic for the Treatment of Alcohol Dependence
Current Drug Abuse Reviews Pulmonary Hypertension in COPD: Pathophysiology and Therapeutic Targets
Current Drug Targets Potential New Targets for Antithrombotic Therapy
Current Pharmaceutical Design Scleroderma Renal Crisis Accompanied by New-Onset Pulmonary Hypertension: An Acute Systemic Endothelial Injury? Case Report and Literature Review
Inflammation & Allergy - Drug Targets (Discontinued) Biologic Therapy in Immune Mediated Inflammatory Disease: Basic Science and Clinical Concepts
Current Drug Safety Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease
Current Neuropharmacology Functional and Molecular Ultrasound Imaging: Concepts and Contrast Agents
Current Medicinal Chemistry Hydrogen Sulphide: Biopharmacological Roles in the Cardiovascular System and Pharmaceutical Perspectives
Current Medicinal Chemistry