title: Structure-activity relationship studies on 1-(5-carboxyindol-1-yl)-propan-2-one inhibitors of human cytosolic phospholipase A2α: variation of the activated ketone moiety.
abstract: Indole-5-carboxylic acids with 3-aryloxy-2-oxopropyl residues in position 1 have been found to be potent inhibitors of human cytosolic phospholipase A(2)α (cPLA(2)α). In course of structure-activity relationship studies, we investigated the effect of the substitution of the electrophilic ketone group in the middle part of the molecule by other polar residues, such as hydroxyimino, azido, acyloxy, acylamino, urea and carbamate, on enzyme inhibition. With an IC(50) of 1.7 μM against cPLA(2)α from human platelets, the 4-fluorophenylcarbamate derivative 23f was the most active of the compounds tested.
authors.affiliation: Institute of Pharmaceutical and Medicinal Chemistry, University of Münster, Münster, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Kaptur
authors.forename: Alwine Schulze
authors.initials: AS
authors.lastname: Elfringhoff
authors.forename: Matthias
authors.initials: M
authors.lastname: Lehr
mesh_terms: D003600:Cytosol / Q000201:enzymology*; D006801:Humans; D007659:Ketones / Q000378:metabolism*; D054467:Phospholipases A2 / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D007659:Ketones; D054467:Phospholipases A2