title: Non-aromatic A-ring replacement in the triaryl bis-sulfone CB2 receptor inhibitors.
abstract: The triaryl bis-sulfone 1 was modified by converting the aryl A-ring to a piperidine ring. The piperidine ring was further elaborated to a spirocyclopropyl piperidine moiety. The effect on CB2 binding potency, rat calcium channel affinity, and CYP 2C9 inhibition is described.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033-0539, USA. eric.gilbert@spcorp.com
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Gilbert
authors.forename: Guowei
authors.initials: G
authors.lastname: Zhou
authors.forename: Michael K C
authors.initials: MK
authors.lastname: Wong
authors.forename: Ling
authors.initials: L
authors.lastname: Tong
authors.forename: Bandarpalle B
authors.initials: BB
authors.lastname: Shankar
authors.forename: Chunli
authors.initials: C
authors.lastname: Huang
authors.forename: Joseph
authors.initials: J
authors.lastname: Kelly
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lavey
authors.forename: Stuart W
authors.initials: SW
authors.lastname: McCombie
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Razia
authors.initials: R
authors.lastname: Rizvi
authors.forename: Youhao
authors.initials: Y
authors.lastname: Dong
authors.forename: Youheng
authors.initials: Y
authors.lastname: Shu
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kozlowski
authors.forename: Neng-Yang
authors.initials: NY
authors.lastname: Shih
authors.forename: R William
authors.initials: RW
authors.lastname: Hipkin
authors.forename: Waldemar
authors.initials: W
authors.lastname: Gonsiorek
authors.forename: Asra
authors.initials: A
authors.lastname: Malikzay
authors.forename: Charles A
authors.initials: CA
authors.lastname: Lunn
authors.forename: Len
authors.initials: L
authors.lastname: Favreau
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lundell
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System; D054314:Drug Inverse Agonism; D006801:Humans; D010880:Piperidines / Q000737:chemistry; D051381:Rats; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D013450:Sulfones / Q000138:chemical synthesis* / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D015220:Calcium Channels; D010880:Piperidines; D043885:Receptor, Cannabinoid, CB2; D013449:Sulfonamides; D013450:Sulfones; C032727:piperidine; D003577:Cytochrome P-450 Enzyme System