Discovery of 1,1-dioxo-1,2,6-thiadiazine-5-carboxamide derivatives as cannabinoid-like molecules with agonist and antagonist activity.
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.
Cano
Carolina
C
Instituto de Química Médica, CSIC, Juan de la Cierva 3, 28006 Madrid, Spain.
Goya
Pilar
P
Paez
Juan Antonio
JA
Girón
Rocío
R
Sánchez
Eva
E
Martín
María Isabel
MI
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
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