title: Tricyclic Pyrazoles. Part 5. Novel 1,4-Dihydroindeno[1,2-c]pyrazole CB2 Ligands Using Molecular Hybridization Based on Scaffold Hopping.
abstract: In search of new selective CB2 ligands, the synthesis and preliminary biological evaluation of novel 1,4-dihydroindeno[1,2-c]pyrazole hybrids of the highly potent prototypicals 5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-N-fenchyl-1H-pyrazole-3-carboxamide 1 and 1-(2,4-dichlorophenyl)-6-methyl-N-(piperidin-1-yl)-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamide 2 are detailed.We postulated that the introduction of those pharmacophoric elements essential for activity of 1 in the tricyclic core of 2 might provide CB2 ligands with further improved receptor selectivity and biological activity. Among the compounds, 6-chloro-7-methyl-1-(2,4-dichlorophenyl)-N-fenchyl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamide (22) exhibited low two digit nanomolar affinity for the cannabinoid CB2R and maintained a high level of CB2-selectivity.
authors.affiliation: Dipartimento di Chimica e Farmacia, Università di Sassari, Via F. Muroni 23/A, 07100 Sassari, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Murineddu
authors.forename: Battistina
authors.initials: B
authors.lastname: Asproni
authors.forename: Stefania
authors.initials: S
authors.lastname: Ruiu
authors.forename: Francesco
authors.initials: F
authors.lastname: Deligia
authors.forename: Matteo
authors.initials: M
authors.lastname: Falzoi
authors.forename: Amedeo
authors.initials: A
authors.lastname: Pau
authors.forename: Brian F
authors.initials: BF
authors.lastname: Thomas
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Gérard A
authors.initials: GA
authors.lastname: Pinna
authors.forename: Luca
authors.initials: L
authors.lastname: Pani
authors.forename: Paolo
authors.initials: P
authors.lastname: Lazzari