PubMed | University of Sassari, CNR Institute of Neuroscience and Italy; KemoTech Srl
Type: | Journal: European journal of medicinal chemistry | Year: 2014
A series of dihydrothienocyclopentapyrazole-based derivatives was synthesized and evaluated for the affinity at CB1 and CB2 receptors. The major term, the 6-methyl-1-(1,4-dichlorophenyl)-N-piperidinyl)-1,4-dihydrothieno[2,3-4,5]cyclopenta[1,2-c]pyrazole-3-carboxamide (6a), displayed a high affinity and good selectivity for CB2 receptors (Ki values of 2.30nM for CB2 receptor and 440nM for CB1 receptors respectively). Subsequent analogue preparation resulted in the identification of compounds such as 6b, 6d, 6e, 6k, 6l, 6m, 6s and 6t that showed 1.3-485 fold selectivity for CB2 receptors with potencies in the 1.1-7.2nM range. These compounds profiled as full agonists at CB2 receptor in an inhibition assay of P-ERK 1/2 up regulation in HL-60 cells.