Tricyclic pyrazoles. 4. Synthesis and biological evaluation of analogues of the robust and selective CB2 cannabinoid ligand 1-(2 ',4 '-dichlorophenyl)-6-methyl-N-piperidin-1-yl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamide

摘要

New analogues (2a-p) of the previously reported CB2 ligands 6-methyl- and 6-chloro-1-(2',4'-dichlorophenyl)-N-piperidin-1-yl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamides (1a,b) have been synthesized and evaluated for cannabinoid receptor affinity. One example, 1-(2',4'-dichlorophenyl)-6-methyl-N-cyclohexyilamine-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamide (2a) was shown to have single digit nanomolar affinity for cannabinoid CB2 receptors. Furthermore, compounds 2a and 2b, as well as lead structures 1a, b, were also shown to be agonist in an in vitro model based on human promyelocytic leukemia HL-60 cells.