title: Structure-activity relationships of indole cytosolic phospholipase A(2)alpha inhibitors: substrate mimetics.
abstract: An SAR effort focused on generating cPLA(2)alpha inhibitors using a substrate mimetic approach is reported. Indole inhibitors of cPLA(2)alpha with promising pharmacokinetic parameters that were active in both an isolated enzyme assay and in cell-based assays were discovered. Modeling these compounds into the cPLA(2)alpha structure validated the assumptions made at the start of the SAR effort.
authors.affiliation: Departments of Chemical and Screening Sciences, Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA. jmckew@wyeth.com
authors.forename: John C
authors.initials: JC
authors.lastname: McKew
authors.forename: Frank
authors.initials: F
authors.lastname: Lovering
authors.forename: James D
authors.initials: JD
authors.lastname: Clark
authors.forename: Jean
authors.initials: J
authors.lastname: Bemis
authors.forename: YiBin
authors.initials: Y
authors.lastname: Xiang
authors.forename: Marina
authors.initials: M
authors.lastname: Shen
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Juan C
authors.initials: JC
authors.lastname: Alvarez
authors.forename: Diane
authors.initials: D
authors.lastname: Joseph-McCarthy
mesh_terms: D001665:Binding Sites; D054513:Group IV Phospholipases A2; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D008968:Molecular Conformation; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011487:Protein Conformation; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: D007202:Indicators and Reagents; D007211:Indoles; D010741:Phospholipases A; D054513:Group IV Phospholipases A2