title: 1-(5-Carboxy- and 5-carbamoylindol-1-yl)propan-2-ones as inhibitors of human cytosolic phospholipase A2alpha: bioisosteric replacement of the carboxylic acid and carboxamide moiety.
abstract: Indole-5-carboxylic acids and -carboxamides with 3-aryloxy-2-oxopropyl residues in position 1 were previously reported to be potent inhibitors of cytosolic phospholipase A(2)alpha (cPLA(2)alpha) isolated from human platelets. In continuation of our attempts to develop novel cPLA(2)alpha inhibitors, a number of derivatives of these substances characterized by bioisosteric replacement of the carboxylic acid and carboxamide functionality, respectively, were prepared. The results of the biological evaluation of the obtained compounds enabled us to gain further insight into structural features critical for cPLA(2)alpha inhibition.
authors.affiliation: Institute of Pharmaceutical and Medicinal Chemistry, University of Münster, Hittorfstrasse 58-62, D-48149 Münster, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Hess
authors.forename: Alwine
authors.initials: A
authors.lastname: Schulze Elfringhoff
authors.forename: Matthias
authors.initials: M
authors.lastname: Lehr
mesh_terms: D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D054513:Group IV Phospholipases A2; D006801:Humans; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D011407:Propane / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D007211:Indoles; D010741:Phospholipases A; D054513:Group IV Phospholipases A2; D011407:Propane