title: Discovery of 1,1-dioxo-1,2,6-thiadiazine-5-carboxamide derivatives as cannabinoid-like molecules with agonist and antagonist activity.
abstract: A series of new 2-substituted 1,1-dioxo-1,2,6-thiadiazine-5-carboxylate derivatives have been prepared from monosubstituted sulfamides in order to obtain N-substituted 1,1-dioxo-1,2,6-thiadiazine-5-carboxamides as novel cannabinoid derivatives, analogues of Rimonabant (SR141716A). Their potential functional activity on cannabinoid receptors has been evaluated in vitro and in vivo in mice, showing that two compounds (37 and 39) behave as cannabinoid agonists in vitro. Their potency is lower than that of the reference compound, WIN 55,212-2, but their efficacy is similar to that of this cannabinoid agonist, although no in vivo activity is observed. Another derivative (38) behaves as a cannabinoid antagonist both in vitro and in vivo, being its efficacy and potency similar to that of the well-known antagonist SR141716A.
authors.affiliation: Instituto de Química Médica, CSIC, Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Cano
authors.forename: Pilar
authors.initials: P
authors.lastname: Goya
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Paez
authors.forename: Rocío
authors.initials: R
authors.lastname: Girón
authors.forename: Eva
authors.initials: E
authors.lastname: Sánchez
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Martín
mesh_terms: D000818:Animals; D048588:Benzoxazines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D002186:Cannabinoids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D002375:Catalepsy; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D007035:Hypothermia; D007274:Injections, Intraperitoneal; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D009025:Morpholines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D009281:Naphthalenes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D010147:Pain Measurement; D010880:Piperidines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D011720:Pyrazoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D043882:Receptors, Cannabinoid; D000077285:Rimonabant; D013237:Stereoisomerism; D013829:Thiadiazines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects
chemical_list: D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D013829:Thiadiazines; 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