title: 1-(2-Carboxyindol-5-yloxy)propan-2-ones as inhibitors of human cytosolic phospholipase A2alpha: synthesis, biological activity, metabolic stability, and solubility.
abstract: Indole-5-carboxylic acids 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 series of structurally related indole-2-carboxylic acids containing 3-aryloxy-2-oxopropoxy residues in position 5 were synthesized and tested for their cPLA(2)alpha-inhibitory potency. Furthermore, the thermodynamic solubility of these compounds and their metabolic stability against rat liver microsomes were evaluated.
authors.affiliation: Institute of Pharmaceutical and Medicinal Chemistry, University of Münster, Hittorfstrasse 58-62, D-48149 Münster, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Fritsche
authors.forename: Alwine Schulze
authors.initials: AS
authors.lastname: Elfringhoff
authors.forename: Jörg
authors.initials: J
authors.lastname: Fabian
authors.forename: Matthias
authors.initials: M
authors.lastname: Lehr
mesh_terms: D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D054513:Group IV Phospholipases A2 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D015394:Molecular Structure; D011422:Propionates / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D011422:Propionates; D054513:Group IV Phospholipases A2