Cannabinoid receptor ligands are potential candidates for the therapy of chronic pain, neuroinflammatory diseases, cancer and obesity. In preceding studies the relevance and structure-activity relationships (SAR) of pyrazole derivatives have been consolidated and clarified, and in the process three series of tricyclic compounds as 1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazoles, 4,5-dihydro-1H-benzo[g]indazoles and 1,4-dihydroindeno[1,2-c]pyrazoles emerged as potent cannabinoid receptor ligands. In the present study five new series of 1,4-dihydroindeno[1,2-c]pyrazole and 1H-benzo[g]indazole carboxamides containing a cyclopropyl, cyclopentyl or cycloexyl substituent were designed and synthesized to evaluate their affinities towards CB1 and CB2 receptors. Among these derivatives, compound 38Am, exibits a high affinity for CB2 receptor (Ki = 4.48nM) together with remarkable selectivity (KiCB1/KiCB1 = 2232). It is interesting to note, in a in vitro neuroinflammatory test, that compound 3Am shows antagonist activity. Unexpectedly, compound 38Aa possess a agonistic biological profile
