title: Sulfonamide derivatives as new potent and selective CB2 cannabinoid receptor agonists.
abstract: A novel series of sulfonamide derivatives 3, the CB(2) receptor agonists, was synthesized and evaluated for activity against the human CB(2) receptor. We first identified sulfonamide 3a, which was obtained by random screening of our in-house chemical library as a moderately active (CB(2) IC(50)=340nM) CB(2) receptor agonist. We then attempted to test its analogues to identify compounds with a high affinity for the CB(2) receptor. One of these, compound 3f, exhibited high affinity for the human CB(2) receptor (IC(50)=16nM) and high selectivity for CB(2) over CB(1) (CB(1) IC(50)/CB(2)IC(50)=106), and behaved as a full CB(2) receptor agonist in the [(35)S]GTPgammaS binding assay (CB(2) EC(50)=7.2nM, E(max)=100%).
authors.affiliation: Medicinal Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd, 1-403 Yoshino-cho, Kita-ku, Saitama-shi, Saitama 331-9530, Japan. hiroshi.ohta@po.rd.taisho.co.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohta
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ishizaka
authors.forename: Mitsukane
authors.initials: M
authors.lastname: Yoshinaga
authors.forename: Aki
authors.initials: A
authors.lastname: Morita
authors.forename: Yasumitsu
authors.initials: Y
authors.lastname: Tomishima
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Toda
authors.forename: Shuji
authors.initials: S
authors.lastname: Saito
mesh_terms: D006801:Humans; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D043885:Receptor, Cannabinoid, CB2; D013449:Sulfonamides