title: Modulation of Wnt signaling through inhibition of secreted frizzled-related protein I (sFRP-1) with N-substituted piperidinyl diphenylsulfonyl sulfonamides.
abstract: The diphenylsulfonyl sulfonamide scaffold represented by 1 (WAY-316606) are small molecule inhibitors of the secreted protein sFRP-1, an endogenous antagonist of the secreted glycoprotein Wnt. Modulators of the Wnt pathway have been proposed as anabolic agents for the treatment of osteoporosis or other bone-related disorders. Details of the structure-activity relationships and biological activity from the first structural class of this scaffold will be discussed.
authors.affiliation: Chemical and Screening Sciences, Wyeth Research, Collegeville, Pennsylvania 19426, USA. moorew2@wyeth.com
authors.forename: William J
authors.initials: WJ
authors.lastname: Moore
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Kern
authors.forename: Ramesh
authors.initials: R
authors.lastname: Bhat
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Commons
authors.forename: Shoichi
authors.initials: S
authors.lastname: Fukayama
authors.forename: Igor
authors.initials: I
authors.lastname: Goljer
authors.forename: Girija
authors.initials: G
authors.lastname: Krishnamurthy
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Magolda
authors.forename: Lisa
authors.initials: L
authors.lastname: Nogle
authors.forename: Keith
authors.initials: K
authors.lastname: Pitts
authors.forename: Barb
authors.initials: B
authors.lastname: Stauffer
authors.forename: Eugene J
authors.initials: EJ
authors.lastname: Trybulski
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Welmaker
authors.forename: Matthew
authors.initials: M
authors.lastname: Wilson
authors.forename: Peter V N
authors.initials: PV
authors.lastname: Bodine
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D020128:Inhibitory Concentration 50; D047908:Intracellular Signaling Peptides and Proteins; D007536:Isomerism; D051379:Mice; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry*; D011485:Protein Binding; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D012886:Skull / Q000187:drug effects; D013329:Structure-Activity Relationship; D013424:Sulfanilamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D000099274:Frizzled-Related Proteins
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D010880:Piperidines; D011506:Proteins; D013424:Sulfanilamides; D051153:Wnt Proteins; D000099274:Frizzled-Related Proteins; C032727:piperidine