Synthesis and pharmacological evaluation of analogs of indole-based cannabimimetic agents.
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.
Mazzoni
Orazio
O
Dipartimento di Chimica Farmaceutica e Tossicologica, Via D. Montesano 49 Università di Napoli Federico II, Naples, Italy.
Diurno
Maria V
MV
di Bosco
Antonio M
AM
Novellino
Ettore
E
Grieco
Paolo
P
Esposito
Giovanni
G
Bertamino
Alessia
A
Calignano
Antonio
A
Russo
Roberto
R
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
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