发明名称 |
2-OXAMIDE INHIBITORS OF PHOSPHOLIPASE A2 ACTIVITY AND CELLULAR ARACHIDONATE RELEASE BASED ON DIPEPTIDES AND PSEUDOPEPTIDES |
摘要 |
The disclosure provides a series of 2-oxoamides based on dipeptides and pseudodipeptides, which were synthesized and their activities toward two human intracellular phospholipases A2 (GIVA CPLA2 and GVIA 1PLA2) and one human secretory phospholipase A2 (GV sPLA2) were evaluated. Derivatives containing a free carboxyl group are selective GIVA cPLA2 inhibitors. A derivative based on the ethyl ester of an ether pseudodipeptide is the first 2-oxoamide, which preferentially inhibits GVIA iPLA2. The effect of 2-oxoamides on the generation of arachidonic acid from RAW 264.7 macrophages was also studied. It was found that selective GIVA cPLA2 inhibitors preferentially inhibited cellular arachidonic acid release; in which one pseudodipeptide gave an IC50 value of 2 µM. |
申请公布号 |
WO2010123832(A2) |
申请公布日期 |
2010.10.28 |
申请号 |
WO2010US31644 |
申请日期 |
2010.04.19 |
申请人 |
THE REGENTS OF THE UNIVERSITY OF CALIFORNIA;DENNIS, EDWARD;KOKOTOS, GEORGE;CONSTANTINOU-KOKOTOU, VIOLETTA |
发明人 |
DENNIS, EDWARD;KOKOTOS, GEORGE;CONSTANTINOU-KOKOTOU, VIOLETTA |
分类号 |
C07C233/56;A61K31/16;A61P29/00 |
主分类号 |
C07C233/56 |
代理机构 |
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代理人 |
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地址 |
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