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
-
Hypertension in Patients with Severe Aortic Stenosis: Emphasis on Antihypertensive Treatment and the Risk of Syncope
Current Hypertension Reviews From Physiome to Pathome: A Systems Biology Model of Major Depressive Disorder and the Psycho-Immune-Neuroendocrine Network
Current Psychiatry Reviews Microwave-Assisted Synthesis of 2,5-Disubstituted-1,3,4-Oxadiazoles
Letters in Organic Chemistry Guide of Hypertensive Crisis Pharmacotherapy
Cardiovascular & Hematological Disorders-Drug Targets Vasopressin in Health and Disease with a Focus on Affective Disorders
Central Nervous System Agents in Medicinal Chemistry Flare-Up Phenomenon of Intradermal Test with Anaphylactic Reaction to Paracetamol (Acetaminophen)
Recent Patents on Inflammation & Allergy Drug Discovery Pegfilgrastim-Apgf (Nyvepria): Biosimilar USFDA Approval for the Treatment of Chemotherapy-induced Febrile Neutropenia and Current Updates on Clinical Trials
Current Drug Targets State of the Art and Development of a Drug-Drug Interaction Large Scale Predictor Based on 3D Pharmacophoric Similarity
Current Drug Metabolism Why is the Inhibition of the Renin-Angiotensin System Effective for Preventing Cardiac Events in Patients with Coronary Risk Factors or Coronary Artery Disease?
Current Cardiology Reviews The Role of IRE1 Signaling in the Central Nervous System Diseases
Current Neuropharmacology Antisense Therapy for Cardiovascular Diseases
Current Pharmaceutical Design Nociceptin/Orphanin FQ Peptide Receptors: Pharmacology and Clinical Implications
Current Drug Targets The Effect of Adult and Pediatric Cardiopulmonary Bypass on Pharmacokinetic and Pharmacodynamic Parameters
Current Clinical Pharmacology Cardiac Biomarkers in Acute Coronary Syndromes: A Review
Current Vascular Pharmacology Impact of Antihypertensive Drug Use on Bone Mineral Density and Osteoporotic Fracture - From an Epidemiological Perspective
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery State of the Art Management of Transfusion-Related Acute Lung Injury (TRALI)
Current Pharmaceutical Design Vascular Inflammation in Hypertension: Targeting Lipid Mediators Unbalance and Nitrosative Stress
Current Hypertension Reviews Microcirculation in Hypertension: An Update on Clinical Significance and Therapy
Current Vascular Pharmacology Towards the Development of Tumor Necrosis Factor (TNF) Sensitizers:Making TNF Work Against Cancer
Current Pharmaceutical Design Inherited Copper Transport Disorders: Biochemical Mechanisms, Diagnosis, and Treatment
Current Drug Metabolism