title: Synthesis and pharmacological evaluation of analogs of indole-based cannabimimetic agents.
abstract: Aminoalkylindoles (AAIs), although structurally dissimilar from the classical cannabinoids, are known to be capable of binding to cannabinoid receptors and of evoking cannabinomimetic responses. With the aim of investigating the structure-activity relationships (SAR) for the binding of non-classical agonists to CB1 and CB2 cannabinoid receptors, we designed and synthesized a series of indole derivatives. The compounds were tested for their analgesic action by formalin test and compared to WIN 55212-2, an AAI acting to the cannabinoid receptors. In receptor binding assay, compound 5 showed affinity for the CB1 receptor comparable to WIN 55212-2.
authors.affiliation: Dipartimento di Chimica Farmaceutica e Tossicologica, Via D. Montesano 49 Università di Napoli Federico II, Naples, Italy.
authors.forename: Orazio
authors.initials: O
authors.lastname: Mazzoni
authors.forename: Maria V
authors.initials: MV
authors.lastname: Diurno
authors.forename: Antonio M
authors.initials: AM
authors.lastname: di Bosco
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Paolo
authors.initials: P
authors.lastname: Grieco
authors.forename: Giovanni
authors.initials: G
authors.lastname: Esposito
authors.forename: Alessia
authors.initials: A
authors.lastname: Bertamino
authors.forename: Antonio
authors.initials: A
authors.lastname: Calignano
authors.forename: Roberto
authors.initials: R
authors.lastname: Russo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D048588:Benzoxazines / Q000494:pharmacology*; D001665:Binding Sites; D001921:Brain / Q000187:drug effects; D016466:CHO Cells; D002186:Cannabinoids / Q000494:pharmacology*; D003198:Computer Simulation; D006224:Cricetinae; D003412:Cricetulus; D007211:Indoles / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D048588:Benzoxazines; D002186:Cannabinoids; D007211:Indoles; D009025:Morpholines; D009281:Naphthalenes; D043884:Receptor, Cannabinoid, CB1; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone