title: Trisubstituted Sulfonamides: a New Chemotype for Development of Potent and Selective CB2Receptor Inverse Agonists.
abstract: An extensive exploration of the SAR of a trisubstituted sulfonamides series led to the identification of39, which is a potent and selective CB2receptor inverse agonist (CB2Ki = 5.4 nM, and CB1Ki = 500 nM). The functional properties measured by cAMP assays indicated that the selected compounds were CB2inverse agonists with high potency values (34, EC50= 8.2 nM, and39, EC50= 2.5 nM). Furthermore, an osteoclastogenesis bioassay indicated that trisubstituted sulfonamide compounds showed great inhibition of osteoclast formation.
authors.affiliation: Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA ; Drug Discovery Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA ; College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Ouyang
authors.affiliation: Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA ; Drug Discovery Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Tong
authors.affiliation: Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA ; Drug Discovery Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Rentian
authors.initials: R
authors.lastname: Feng
authors.affiliation: Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA ; Drug Discovery Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA ; Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Kyaw-Zeyar
authors.initials: KZ
authors.lastname: Myint
authors.affiliation: Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA ; Drug Discovery Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA ; Drug Discovery Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA ; Pittsburgh Chemical Methods and Library Development Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA ; Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA ; Department of Structural Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Xiang-Qun
authors.initials: XQ
authors.lastname: Xie
keywords: cannabinoid receptors; inverse agonists; osteoclast inhibitors; trisubstituted sulfonamides
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