Perspectives of Cannabinoid Type 2 Receptor (CB2R) Ligands in Neurodegenerative Disorders: Structure-Affinity Relationship (SAfiR) and Structure-Activity Relationship (SAR) Studies.
Francesco SpinelliElena CapparelliCarmen AbateNicola A ColabufoMarialessandra ContinoPublished in: Journal of medicinal chemistry (2017)
Up-regulation of CB2R on activated microglial cells, the first step in neurodegeneration, has been widely demonstrated, and this finding makes the receptor a promising target in the early diagnosis and treatment of several neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and multiple sclerosis (MS). The development of CB2R PET ligands could help demonstrate the neurodegenerative pathogenesis, thus providing useful tools for characterizing the role of neuroinflammation in the progression of these disorders. CB2R agonists and inverse agonists have emerged as neuroprotective agents, and CB2R agonists have entered several clinical trials. CB2R ligands have therefore received great attention, and different molecular scaffolds have been selected to target CB2R subtypes. This review is focused on structure-activity relationship (SAR) and structure-affinity relationship (SAfiR) studies performed on different scaffolds with the aim to identify the molecular features useful for the design of both therapeutic and diagnostic agents.
Keyphrases
- structure activity relationship
- multiple sclerosis
- clinical trial
- lipopolysaccharide induced
- induced apoptosis
- computed tomography
- randomized controlled trial
- tissue engineering
- traumatic brain injury
- lps induced
- mass spectrometry
- ms ms
- oxidative stress
- brain injury
- cell cycle arrest
- spinal cord
- study protocol
- pet ct
- cell death
- mild cognitive impairment
- cerebral ischemia
- pet imaging
- phase ii
- subarachnoid hemorrhage
- placebo controlled