title: 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.
abstract: New analogues (2a-p) of the previously reported CB(2) 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 CB(2) 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.
authors.affiliation: Dipartimento Farmaco Chimico Tossicologico, Università di Sassari, Via F. Muroni 23/A, 07100 Sassari, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Murineddu
authors.forename: Paolo
authors.initials: P
authors.lastname: Lazzari
authors.forename: Stefania
authors.initials: S
authors.lastname: Ruiu
authors.forename: Angela
authors.initials: A
authors.lastname: Sanna
authors.forename: Giovanni
authors.initials: G
authors.lastname: Loriga
authors.forename: Ilaria
authors.initials: I
authors.lastname: Manca
authors.forename: Matteo
authors.initials: M
authors.lastname: Falzoi
authors.forename: Christian
authors.initials: C
authors.lastname: Dessì
authors.forename: Maria M
authors.initials: MM
authors.lastname: Curzu
authors.forename: Giorgio
authors.initials: G
authors.lastname: Chelucci
authors.forename: Luca
authors.initials: L
authors.lastname: Pani
authors.forename: Gérard A
authors.initials: GA
authors.lastname: Pinna
mesh_terms: D018922:HL-60 Cells; D006801:Humans; D007192:Indenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis; D010766:Phosphorylation; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: D007192:Indenes; D008024:Ligands; D010880:Piperidines; D011720:Pyrazoles; D043885:Receptor, Cannabinoid, CB2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3