title: Tricyclic pyrazoles. Part 2: Synthesis and biological evaluation of novel 4,5-dihydro-1H-benzo[g]indazole-based ligands for cannabinoid receptors.
abstract: A series of 4,5-dihydro-1H-benzo[g]indazole-3-carboxamides (2a-k) as analogues of the previously reported CB(2) ligands 6-chloro- and 6-methyl-1-(2',4'-dichlorophenyl)-N-piperidin-1-yl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamides (1a,b) was synthesized and their affinity and selectivity towards CB(1) and CB(2) receptors were evaluated. Several of the new compounds (2a,b,c,d and i) exhibited CB(1) affinity in the nanomolar range with moderate or negligible affinity towards CB(2) receptors. Compounds 2a and c increased intestinal propulsion in mouse. Their pro-kinetic effects were reversed by the reference CB agonist CP-55,940. Consequently, in vivo CB(1) antagonistic activity was highlighted for these compounds.
authors.affiliation: Dipartimento Farmaco Chimico Tossicologico, Università di Sassari, via F. Muroni 23/A, 07100 Sassari, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Murineddu
authors.forename: Stefania
authors.initials: S
authors.lastname: Ruiu
authors.forename: Jean-Mario
authors.initials: JM
authors.lastname: Mussinu
authors.forename: Giovanni
authors.initials: G
authors.lastname: Loriga
authors.forename: Giuseppe E
authors.initials: GE
authors.lastname: Grella
authors.forename: Mauro A M
authors.initials: MA
authors.lastname: Carai
authors.forename: Paolo
authors.initials: P
authors.lastname: Lazzari
authors.forename: Luca
authors.initials: L
authors.lastname: Pani
authors.forename: Gérard A
authors.initials: GA
authors.lastname: Pinna
mesh_terms: D000818:Animals; D063387:Cannabinoid Receptor Antagonists; D005772:Gastrointestinal Transit / Q000187:drug effects / Q000502:physiology; D007191:Indazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D043882:Receptors, Cannabinoid / Q000378:metabolism; D000077285:Rimonabant; D013329:Structure-Activity Relationship
chemical_list: C503151:4,5-dihydro-1H-benzo(g)indazole; D063387:Cannabinoid Receptor Antagonists; D007191:Indazoles; D008024:Ligands; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D000077285:Rimonabant