title: Facile synthesis, ex-vivo and in vitro screening of 3-sulfonamide derivative of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide (SR141716) a potent CB1 receptor antagonist.
abstract: Facile synthesis of biaryl pyrazole sulfonamide derivative of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide (SR141716, 1) and an investigation of the effect of replacement of the -CO group in the compound 1 by the -SO(2) group in the aminopiperidine region is reported. Primary ex-vivo pharmacological testing and in vitro screening of sulfonamide derivative 2 showed the loss of CB1 receptor antagonism.
authors.affiliation: Department of Medicinal Chemistry, Zydus Research Centre, Cadila Healthcare Ltd., Sarkhej-Bavla N. H.8A, Moraiya, Ahmedabad 382210, India. brijeshsrivastava@zyduscadila.com
authors.forename: Brijesh
authors.initials: B
authors.lastname: Kumar Srivastava
authors.forename: Rina
authors.initials: R
authors.lastname: Soni
authors.forename: Jayendra Z
authors.initials: JZ
authors.lastname: Patel
authors.forename: Satadru
authors.initials: S
authors.lastname: Jha
authors.forename: Sandeep A
authors.initials: SA
authors.lastname: Shedage
authors.forename: Neha
authors.initials: N
authors.lastname: Gandhi
authors.forename: Kalapatapu V V M
authors.initials: KV
authors.lastname: Sairam
authors.forename: Vishwanath
authors.initials: V
authors.lastname: Pawar
authors.forename: Nisha
authors.initials: N
authors.lastname: Sadhwani
authors.forename: Prasenjit
authors.initials: P
authors.lastname: Mitra
authors.forename: Mukul R
authors.initials: MR
authors.lastname: Jain
authors.forename: Pankaj R
authors.initials: PR
authors.lastname: Patel
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D020128:Inhibitory Concentration 50; D051379:Mice; D008956:Models, Chemical; D008968:Molecular Conformation; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D000077285:Rimonabant; D013449:Sulfonamides / Q000737:chemistry*
chemical_list: D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D013449:Sulfonamides; D000077285:Rimonabant