Description of a bivalent cannabinoid ligand with hypophagic properties.
A series of bivalent cannabinoid ligands is proposed. The synthesis of double amides based on the rimonabant structure separated by an alkyl chain and the evaluation of their affinities for cannabinoid receptors are reported. The data of 4d confirmed that a bivalent structure is a suitable scaffold for CB1 cannabinoid receptor binding. The compound 4d was selected for in vitro and in vivo pharmacological evaluations. Moreover, intraperitoneal administration of 4d to food-deprived rats resulted in a dose-dependent inhibition of feeding that was maintained up to 240 min.
Instituto de Química Médica, CSIC, Madrid, Spain.
Cristina
C
Fernández-Fernández
Juan
J
Decara
Francisco J
FJ
Bermúdez-Silva
Eva
E
Sánchez
Paula
P
Morales
María
M
Gómez-Cañas
María
M
Gómez-Ruíz
Luis F
LF
Callado
Pilar
P
Goya
Fernando
F
Rodríguez de Fonseca
M Isabel
MI
Martín
Javier
J
Fernández-Ruíz
J Javier
JJ
Meana
Nadine
N
Jagerovic
D000818:Animals; D063387:Cannabinoid Receptor Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D015195:Drug Design; D005247:Feeding Behavior / Q000187:drug effects*; D005508:Food Deprivation; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*; D000077285:Rimonabant; D013329:Structure-Activity Relationship; D014162:Transfection
D063387:Cannabinoid Receptor Antagonists; D008024:Ligands; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant