Abstract
The CB1 receptor is found principally in the central nervous system and is responsible for the overt physiological effects of cannabinoids. In contrast, the CB2 receptor is expressed primarily in the immune system and is responsible for few, if any, obvious behavioral effects. Although many cannabinoid receptor ligands show little, or at best modest, selectivity for either receptor, a number of synthetic compounds are known which have significant selectivity for the CB2 receptor. These include cannabimimetic indoles, such as 1-propyl-2-methyl-3-(1-naphthoyl)indole (JWH-015) and 1-(2,3-dichlorobenzoyl)-2-methyl-3-(2-[1-morpholino] ethyl)-5-methoxyindole (L768242), both of which have good affinity for the CB2 receptor, but weak affinity for the CB1 receptor. Efforts have been made to develop structure-activity relationships (SAR) at CB2 for cannabimimetic indoles, but with limited success. Several derivatives of traditional dibenzopyran based cannabinoids have also been found to have significant selectivity for the CB2 receptor. These include 1- methoxyΔ8-THC derivatives, 1-methoxyΔ8-THC-DMH (L759633), 1-methoxyΔ9(11)-THC-DMH (L759656), and 1-methoxy-3-(1,1-dimethylhexyl)Δ8-THC (JWH-229), plus a number of 1-deoxyΔ8-THC analogues. In particular, 1-deoxy-3-(1,1-dimethylbutyl)Δ8-THC (JWH-133) shows two hundred-fold selectivity for the CB2 receptor. Very recently several compounds belonging to other structural groups have also shown selectivity for the CB2 receptor. This review will describe the current status of the results of these studies and discuss the SAR for these classes of ligands.
Keywords: cannabinoids, deoxy cannabinoids, cb receptor, aminoalkylindoles
Mini-Reviews in Medicinal Chemistry
Title: CB2 Receptor Ligands
Volume: 5 Issue: 7
Author(s): J. W. Huffman
Affiliation:
Keywords: cannabinoids, deoxy cannabinoids, cb receptor, aminoalkylindoles
Abstract: The CB1 receptor is found principally in the central nervous system and is responsible for the overt physiological effects of cannabinoids. In contrast, the CB2 receptor is expressed primarily in the immune system and is responsible for few, if any, obvious behavioral effects. Although many cannabinoid receptor ligands show little, or at best modest, selectivity for either receptor, a number of synthetic compounds are known which have significant selectivity for the CB2 receptor. These include cannabimimetic indoles, such as 1-propyl-2-methyl-3-(1-naphthoyl)indole (JWH-015) and 1-(2,3-dichlorobenzoyl)-2-methyl-3-(2-[1-morpholino] ethyl)-5-methoxyindole (L768242), both of which have good affinity for the CB2 receptor, but weak affinity for the CB1 receptor. Efforts have been made to develop structure-activity relationships (SAR) at CB2 for cannabimimetic indoles, but with limited success. Several derivatives of traditional dibenzopyran based cannabinoids have also been found to have significant selectivity for the CB2 receptor. These include 1- methoxyΔ8-THC derivatives, 1-methoxyΔ8-THC-DMH (L759633), 1-methoxyΔ9(11)-THC-DMH (L759656), and 1-methoxy-3-(1,1-dimethylhexyl)Δ8-THC (JWH-229), plus a number of 1-deoxyΔ8-THC analogues. In particular, 1-deoxy-3-(1,1-dimethylbutyl)Δ8-THC (JWH-133) shows two hundred-fold selectivity for the CB2 receptor. Very recently several compounds belonging to other structural groups have also shown selectivity for the CB2 receptor. This review will describe the current status of the results of these studies and discuss the SAR for these classes of ligands.
Export Options
About this article
Cite this article as:
Huffman W. J., CB2 Receptor Ligands, Mini-Reviews in Medicinal Chemistry 2005; 5 (7) . https://dx.doi.org/10.2174/1389557054368844
DOI https://dx.doi.org/10.2174/1389557054368844 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
Natural Products in Drug Discovery
Natural products have always been one of the important ways of drug discovery due to their novel skeleton and diverse functional group characteristics. According to statistics, between 1981 and 2019, the FDA approved a total of 1,394 small molecule drugs for marketing, of which 930 marketed drugs originated from the ...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
Related Articles
-
Abelson Tyrosine-Protein Kinase 1 as Principal Target for Drug Discovery Against Leukemias. Role of the Current Computer-Aided Drug Design Methodologies
Current Topics in Medicinal Chemistry 2,4,6-Trichlorophenylhydrazine Schiff Bases as DPPH Radical and Super Oxide Anion Scavengers
Medicinal Chemistry Current State and Perspectives of 3D-QSAR
Current Topics in Medicinal Chemistry Implications of Epigenetic Mechanisms and their Targets in Cerebral Ischemia Models
Current Neuropharmacology Efficacy of Yun Zhi (Coriolus versicolor) on Survival in Cancer Patients: Systematic Review and Meta-Analysis
Recent Patents on Inflammation & Allergy Drug Discovery Graphical Abstracts
Medicinal Chemistry A Recent Perspective on Discovery and Development of Diverse Therapeutic Agents Inspired from Isatin Alkaloids
Current Topics in Medicinal Chemistry Design and Synthesis of Tri-substituted Imidazole Derivatives as CD73 Inhibitors for Their Anticancer Activity
Letters in Drug Design & Discovery Arylpiperazines with Affinity Toward a1-Adrenergic Receptors
Current Medicinal Chemistry Integration of Internet of Things with Quantum Dots: A State-of-the-art of Medicine
Current Pharmaceutical Design Biomarkers and Osteosarcoma and IGF
Recent Patents on Biomarkers 1,4-Dihydropyridine Scaffold in Medicinal Chemistry, The Story so Far And Perspectives (Part 1): Action in Ion Channels and GPCRs
Current Medicinal Chemistry Nanoparticle Interaction with Biomolecules: How it Shapes the Nano-Effects on Immunity
Current Bionanotechnology (Discontinued) Aptamer-based Emerging Tools for Viral Biomarker Detection: A Focus on SARS-CoV-2
Current Medicinal Chemistry Structural Aspects of Drugability and Selectivity of Protein Kinases in Inflammation
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Various Novel Erythromycin Derivatives Obtained by Different Modifications: Recent Advance in Macrolide Antibiotics
Mini-Reviews in Medicinal Chemistry Molecular Properties Prediction, Docking Studies, and Antimicrobial Screening of 1,3,4-Thiadiazole and s-Triazole Derivatives
Current Computer-Aided Drug Design Recent Patents in Exhaust Heat Recovery Units
Recent Patents on Mechanical Engineering Exploring Pyrimidine Pharmacophore as Thymidine Monophosphate Kinase Inhibitors for Antitubercular Activity: A Review
Current Topics in Medicinal Chemistry Improving Health Care for Children with Chronic Conditions: Toward a “Wholistic” Approach
Current Pediatric Reviews