Potent inhibitors of lipoprotein-associated phospholipase A2: Benzaldehyde O-heterocycle-4-carbonyloxime = 강력한 Lp-PLA2의 억제제인 벤즈알데히드 O-헤테로사이클-4-카르보닐옥심의 개발

Cited 24 time in scopus
Metadata Downloads
Title
Potent inhibitors of lipoprotein-associated phospholipase A2: Benzaldehyde O-heterocycle-4-carbonyloxime = 강력한 Lp-PLA2의 억제제인 벤즈알데히드 O-헤테로사이클-4-카르보닐옥심의 개발
Author(s)
Hyung Jae Jung; Yong-Dae Park; Ho Yong Park; I Y Jeong; Tae Sook JeongWoo Song Lee
Bibliographic Citation
Bioorganic & Medicinal Chemistry Letters, vol. 16, no. 21, pp. 5576-5579
Publication Year
2006
Abstract
A series of multi-substituted oximes were prepared and their potencies for inhibiting lipoprotein-associated phospholipase A2 (Lp-PLA2) activity were evaluated in vitro. Among them, compounds 3a, 3b, and 3m were identified to display a micromolar potency for inhibiting Lp-PLA2 in whole human plasma and isolated human LDL. Based on these results, structure-activity relationship was studied on modification of three parts of R1, R2, and R3 to identify a potent pharmacophore for Lp-PLA2. In an attempt to introduce various functional groups at R2 and R3, we discovered that replacement of less lipophilic groups led to an increase of inhibitory activity. Among the tested oxime derivatives, cyano- and morpholino-substituted analogue 4f at R2 and R3 had the highest potency with an IC50 value of 0.05 μM in whole human plasma.
Keyword
Lp-PLA2 inhibitor
ISSN
0960-894X
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bmcl.2006.08.031
Type
Article
Appears in Collections:
Jeonbuk Branch Institute > Functional Biomaterial Research Center > 1. Journal Articles
Division of Biomedical Research > Microbiome Convergence Research Center > 1. Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.