title: Control of chronic inflammation with pathway selective estrogen receptor ligands.
abstract: The discovery of novel intervention points in the inflammatory pathway has been a focus of drug development in recent years. We have identified pathway selective ligands for the estrogen receptor (ER) that inhibit NF-kappaB mediated inflammatory gene expression causing a reduction of cytokines, chemokines, adhesion molecules and inflammatory enzymes. SAR development of a series of 4-(Indazol-3-yl)-phenols has led to the identification of WAY-169916 an orally active non-steroidal ligand with the potential use in the treatment of inflammatory diseases without the classical proliferative effects associated with non-selective estrogens.
authors.affiliation: Chemical and Screening Sciences, Wyeth Research, 500 Arcola Rd, Collegeville, PA 19426, USA. steffar@wyeth.com
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Steffan
authors.forename: Edward
authors.initials: E
authors.lastname: Matelan
authors.forename: Mark A
authors.initials: MA
authors.lastname: Ashwell
authors.forename: William J
authors.initials: WJ
authors.lastname: Moore
authors.forename: William R
authors.initials: WR
authors.lastname: Solvibile
authors.forename: Eugene
authors.initials: E
authors.lastname: Trybulski
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Chadwick
authors.forename: Susan
authors.initials: S
authors.lastname: Chippari
authors.forename: Thomas
authors.initials: T
authors.lastname: Kenney
authors.forename: Richard C
authors.initials: RC
authors.lastname: Winneker
authors.forename: Amy
authors.initials: A
authors.lastname: Eckert
authors.forename: Lisa
authors.initials: L
authors.lastname: Borges-Marcucci
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Adelman
authors.forename: Zhang
authors.initials: Z
authors.lastname: Xu
authors.forename: Lydia
authors.initials: L
authors.lastname: Mosyak
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Harnish
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002908:Chronic Disease; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology*; D008024:Ligands; D015394:Molecular Structure; D011720:Pyrazoles / Q000627:therapeutic use*; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors* / Q000276:immunology*; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008024:Ligands; D011720:Pyrazoles; D011960:Receptors, Estrogen; C499198:WAY-169916