RESEARCH ARTICLE
Tricyclic Pyrazoles. Part 5. Novel 1,4-Dihydroindeno[1,2-c]pyrazole CB2 Ligands Using Molecular Hybridization Based on Scaffold Hopping
Gabriele Murineddu a, *, Battistina Asproni a, Stefania Ruiu b, Francesco Deligia a, Matteo Falzoi b, Amedeo Pau a, Brian F Thomas c, Yanan Zhang c, Gérard A Pinna a, Luca Pani b, #, Paolo Lazzari a, d, *
Article Information
Identifiers and Pagination:
Year: 2012Volume: 6
First Page: 1
Last Page: 14
Publisher ID: TOMCJ-6-1
DOI: 10.2174/1874104501206010001
Article History:
Received Date: 11/11/2011Revision Received Date: 7/3/2012
Acceptance Date: 22/3/2012
Electronic publication date: 17/5/2012
Collection year: 2012

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
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.