title: Design of new potent and selective secretory phospholipase A2 inhibitors. Part 5: synthesis and biological activity of 1-alkyl-4-[4,5-dihydro-1,2,4-[4H]-oxadiazol-5-one-3-ylmethylbenz-4'-yl(oyl)] piperazines.
abstract: Among the different PLA(2)s identified to date, the group IIA secretory PLA(2) (sPLA(2) GIIA) is implied in diverse pathological conditions. In this work we describe the synthesis, inhibitory activities, and structure-activity relationships (SAR) of a new class of substituted piperazine derivatives. The in vitro fluorimetric assay using two groups of enzymes, GIB and GIIA, revealed several compounds as highly potent inhibitors (IC(50)=0.1 microM). The in vivo activity assessed by ip or per os administration in a carrageenan-induced edema test in rats showed that two compounds proved to be as potent as indomethacin (10 mg/kg).
authors.affiliation: Laboratoire de Pharmacochimie Moléculaire, Unité de Pharmacochimie Moléculaire et Systèmes Membranaires E.A. 2381, Université Paris 7-Denis Diderot, Case 7066, 2 Place Jussieu, 75251 Paris Cedex 05, France.
authors.forename: Latifa
authors.initials: L
authors.lastname: Boukli
authors.forename: Mohamed
authors.initials: M
authors.lastname: Touaibia
authors.forename: Nadia
authors.initials: N
authors.lastname: Meddad-Belhabich
authors.forename: Atimé
authors.initials: A
authors.lastname: Djimdé
authors.forename: Chang-Ha
authors.initials: CH
authors.lastname: Park
authors.forename: Jung-Joo
authors.initials: JJ
authors.lastname: Kim
authors.forename: Joo-Hyoung
authors.initials: JH
authors.lastname: Yoon
authors.forename: Aazdine
authors.initials: A
authors.lastname: Lamouri
authors.forename: Françoise
authors.initials: F
authors.lastname: Heymans
mesh_terms: D000478:Alkylation; D000818:Animals; D001554:Benzene / Q000737:chemistry*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006859:Hydrogen / Q000737:chemistry*; D008745:Methylation; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D054497:Phospholipases A2, Secretory / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D004791:Enzyme Inhibitors; D010080:Oxazoles; D010879:Piperazines; D006859:Hydrogen; D054497:Phospholipases A2, Secretory; D001554:Benzene