title: Inhibition of secretory phospholipase A2. 2-Synthesis and structure-activity relationship studies of 4,5-dihydro-3-(4-tetradecyloxybenzyl)-1,2,4-4H-oxadiazol-5-one (PMS1062) derivatives specific for group II enzyme.
abstract: We have recently reported the discovery of a series of specific inhibitors of human group IIA phospholipase A(2) (hGIIA PLA(2)) to display promising in vitro and in vivo properties. Here we describe the influence of different structural modifications on the specificity and potency against hGIIA PLA(2) versus porcine group IB PLA(2). The SAR results, as well as the logP and pK(a) values of oxadiazolone determined in this work, provide important information towards the comprehension of the mode of action of this kind of compounds.
authors.affiliation: Unité de Pharmacochimie Moléculaire et Systèmes Membranaires (EA2381), Laboratoire de Pharmacochimie Moléculaire, Université Paris 7-Denis Diderot, Case 7066, 2, Place Jussieu, 75251 Paris Cedex 05, France.
authors.forename: Chang-Zhi
authors.initials: CZ
authors.lastname: Dong
authors.forename: Azali
authors.initials: A
authors.lastname: Ahamada-Himidi
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Plocki
authors.forename: Darina
authors.initials: D
authors.lastname: Aoun
authors.forename: Mohamed
authors.initials: M
authors.lastname: Touaibia
authors.forename: Nadia
authors.initials: N
authors.lastname: Meddad-Bel Habich
authors.forename: Jack
authors.initials: J
authors.lastname: Huet
authors.forename: Catherine
authors.initials: C
authors.lastname: Redeuilh
authors.forename: Jean-Edouard
authors.initials: JE
authors.lastname: Ombetta
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Godfroid
authors.forename: France
authors.initials: F
authors.lastname: Massicot
authors.forename: Françoise
authors.initials: F
authors.lastname: Heymans
mesh_terms: D000478:Alkylation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000145:classification / Q000378:metabolism*; D054467:Phospholipases A2; D013329:Structure-Activity Relationship
chemical_list: C502392:4,5-dihydro-3-(4-tetradecyloxybenzyl)-1,2,4-4H-oxadiazol-5-one; D004791:Enzyme Inhibitors; D010080:Oxazoles; D010741:Phospholipases A; D054467:Phospholipases A2