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.
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.
Dong
Chang-Zhi
CZ
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.
Ahamada-Himidi
Azali
A
Plocki
Stéphanie
S
Aoun
Darina
D
Touaibia
Mohamed
M
Meddad-Bel Habich
Nadia
N
Huet
Jack
J
Redeuilh
Catherine
C
Ombetta
Jean-Edouard
JE
Godfroid
Jean-Jacques
JJ
Massicot
France
F
Heymans
Françoise
F
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
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