New Approaches in the Design and Development of Cannabinoid Receptor Ligands: Multifunctional and Bivalent Compounds

• Published in: ChemMedChem 2015-05, Vol.10 (5), p.773-786
• Main Authors: Nimczick, Martin, Decker, Michael
• Format: Article
• Language: English
• Subjects: bivalent ligands; Cannabinoid Receptor Agonists - chemical synthesis; Cannabinoid Receptor Agonists - chemistry; Cannabinoid Receptor Agonists - pharmacology; Cannabinoid Receptor Antagonists - chemical synthesis; Cannabinoid Receptor Antagonists - chemistry; Cannabinoid Receptor Antagonists - pharmacology; cannabinoid receptors; Drug Design; drug design strategies; G protein-coupled receptors; Humans; Ligands; Molecular Structure; multifunctional ligands; Receptors, Cannabinoid - metabolism
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.201500041

Since the identification of the endocannabinoid system, two G protein‐coupled receptors (GPCRs) of this complex system were identified and characterized: cannabinoid receptors type 1 (CB1R) and type 2 (CB2R). In addition to orthosteric and subsequently allosteric ligands, new strategies have been used to target CBRs. Bivalent ligands and multifunctional ligands acting at diverse biological targets have been designed, synthesized, and characterized for both CBRs. Due to their altered receptor binding and pharmacological profiles, they are interesting tools to explore CBR functions and their interactions with other physiological systems. Moreover, this approach may bear therapeutic advantages in the therapy of CBR‐related disorders, especially multifactorial diseases. Promising prospects include anorectics with fewer side effects, analgesics with decreased tolerance, and therapeutics with multiple pharmacological activities for the treatment of cancer, inflammation, multiple sclerosis, Huntington’s and Alzheimer’s diseases. Bivalent and multifunctional ligands acting at diverse biological targets were recently designed, synthesized and characterized for both cannabinoid receptor subtypes (CBRs). Due to their altered receptor binding and pharmacological profiles, they represent interesting tools to explore CBR functions and their interactions with other physiological systems. Moreover, this approach may bear therapeutic advantages in the therapy of CBR‐related disorders, especially multifactorial diseases.