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-1
H
-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.