New low-density lipoprotein receptor upregulators acting via a novel mechanism

被引：11

作者：

Ashton, MJ ^{[1
]}

Brown, TJ ^{[1
]}

Fenton, G ^{[1
]}

Halley, F ^{[1
]}

Harper, MF ^{[1
]}

Lockey, PM ^{[1
]}

Porter, B ^{[1
]}

Roach, AG ^{[1
]}

Stuttle, KAJ ^{[1
]}

Vicker, N ^{[1
]}

Walsh, RJA ^{[1
]}

机构：

[1] RHONE POULENC RORER,DAGENHAM RES CTR,DAGENHAM RM10 7XS,ESSEX,ENGLAND

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1996年 / 39卷 / 17期

关键词：

D O I：

10.1021/jm960153q

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and biological activity of a new series of benzamides and related compounds that upregulate the expression of the low-density lipoprotein (LDL) receptor in human hepatocytes (HepG2 cells) by a novel mechanism are described. The lead compound, N-[5-[(3-cyclohexylpropionyl)amino]-2-methylphenyl]-4-hydroxybenzamide (1, RPR102359), increased the expression of the LDL receptors in HepG2 cells by 80% when tested at a concentration of 3 mu M. Mevinolin (lovastatin) was found to increase the LDL receptor expression by 70% at the same concentration. In contrast to mevinolin, 1 was found to have no effect on cholesterol biosynthesis in liver homogenates or in HepG2 cells at doses where substantial upregulation of the LDL receptor was observed and thus stimulated LDL receptor expression by a novel mechanism.

引用

页码：3343 / 3356

页数：14

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