title: Synthesis, structure-activity relationship, and evaluation of SR141716 analogues: development of central cannabinoid receptor ligands with lower lipophilicity.
abstract: Exploration of the central CB1 cannabinoid receptors using positron emission tomography (PET) will allow for an understanding of the pharmacological and physiological role played by these receptors in the CNS. Current tracers are highly lipophilic compounds that exhibit very high nonspecific to specific binding ratios and as a result are inapt for use in humans. We have synthesized a series of less lipophilic analogues of SR141716 to serve as potential radioligands. Binding affinities of the series and a functional electrophysiological assay of three of our compounds have been presented.
authors.affiliation: Neuroimaging Research Branch and Cellular Neurophysiology Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, USA.
authors.forename: Reeti
authors.initials: R
authors.lastname: Katoch-Rouse
authors.forename: Olga A
authors.initials: OA
authors.lastname: Pavlova
authors.forename: Tara
authors.initials: T
authors.lastname: Caulder
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Hoffman
authors.forename: Alexey G
authors.initials: AG
authors.lastname: Mukhin
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Horti
mesh_terms: D000818:Animals; D048588:Benzoxazines; D002186:Cannabinoids / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D066298:In Vitro Techniques; D008024:Ligands; D008564:Membrane Potentials; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000502:physiology; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077285:Rimonabant; D013329:Structure-Activity Relationship; D014055:Tomography, Emission-Computed
chemical_list: D048588:Benzoxazines; D002186:Cannabinoids; D008024:Ligands; D009025:Morpholines; C471874:N-(1-piperidinyl)-1-(2,4-dichlorophenyl)-4-methyl-5-(4-methoxyphenyl)pyrazolecarboxamide; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D000077285:Rimonabant