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
-
The Role of Oxidative Stress on Necrotizing Enterocolitis in Very Low Birth Weight Infants
Current Pediatric Reviews Sudden Infant Death Syndrome: Implications of Altered Physiological Control During Sleep
Current Pediatric Reviews Monoamino Oxidase A: An Interesting Pharmacological Target for the Development of Multi-Target QSAR
Mini-Reviews in Medicinal Chemistry Obstructive Sleep Apnoea Syndrome and Diabetes. Fortuitous Association or Interaction?
Current Diabetes Reviews Ligand-Based Peptide Design and Combinatorial Peptide Libraries to Target G Protein-Coupled Receptors
Current Pharmaceutical Design Polypharmacy in Cardiovascular Medicine: Problems and Promises!
Cardiovascular & Hematological Agents in Medicinal Chemistry α-Synuclein Misfolding and Neurodegenerative Diseases
Current Protein & Peptide Science Innovative Therapeutic Strategies for Restoring Lymphocyte Functions in Septic Patients
Inflammation & Allergy - Drug Targets (Discontinued) Can We Move Forward After ADVANCE?
Vascular Disease Prevention (Discontinued) Sex Steroid Hormones, Cardiovascular Diseases and The Metabolic Syndrome
Cardiovascular & Hematological Agents in Medicinal Chemistry The Pharmacological Management of Delirium in Critical Illness
Current Drug Therapy HIF Prolyl 4-Hydroxylases and their Potential as Drug Targets
Current Pharmaceutical Design Therapeutic Perspectives of Inhibitors of Endocannabinoid Degradation
Current Drug Targets - CNS & Neurological Disorders Vasopressin-Receptor Antagonists: A New Class of Agents for the Treatment of Hyponatremia
Endocrine, Metabolic & Immune Disorders - Drug Targets Healthy Properties of Garlic
Current Nutrition & Food Science Structural and Functional Characterization of a γ-Type Phospholipase A2 Inhibitor from Bothrops jararacussu Snake Plasma
Current Topics in Medicinal Chemistry Optical and Multimodal Peptide-Based Probes for In Vivo Molecular Imaging
Anti-Cancer Agents in Medicinal Chemistry Barker and Brenner: A Basis for Hypertension?
Current Hypertension Reviews Antiprotozoal Agents: An Overview
Anti-Infective Agents in Medicinal Chemistry N-Acetylcysteine for the Treatment of Obsessive-Compulsive Disorder
Current Psychiatry Reviews