Polyunsaturated fatty acid anilides as inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT)

被引：7

作者：

Matsuyama, N ^{[1
]}

Kosaka, T ^{[1
]}

Fukuhara, M ^{[1
]}

Soda, Y ^{[1
]}

Mizuno, K ^{[1
]}

机构：

[1] Azwell Inc, R&D Facil, Ibaraki, Osaka 5670806, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1999年 / 9卷 / 14期

关键词：

D O I：

10.1016/S0960-894X(99)00330-3

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of polyunsaturated fatty acid anilides were synthesized and evaluated as ACAT inhibitors. Compound 24 had potent inhibitory activity against microsomal ACAT derived from U937, HepG2 and Caco-2 cell lines. Therefore, it might be expected to act as an antiarteriosclerotic and hypocholesterolemic agent. Interestingly, the ACAT inhibitory potency of 24 varied significantly depending on the source of the enzyme. (C) 1999 Elsevier Science Ltd. All rights reserved.

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页码：2039 / 2042

页数：4

相关论文

共 16 条

[1] Identification of a form of acyl-CoA:cholesterol acyltransferase specific to liver and intestine in nonhuman primates [J].

Anderson, RA ;

Joyce, C ;

Davis, M ;

Reagan, JW ;

Clark, M ;

Shelness, GS ;

Rudel, LL .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (41) :26747-26754

[2] ACAT-2, a second mammalian acyl-CoA:cholesterol acyltransferase -: Its cloning, expression, and characterization [J].

Cases, S ;

Novak, S ;

Zheng, YW ;

Myers, HM ;

Lear, SR ;

Sande, E ;

Welch', CB ;

Lusis, AJ ;

Spencer, TA ;

Krause, BR ;

Erickson, SK ;

Farese, RV .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (41) :26755-26764

[3] Acyl CoA:cholesterol acyltransferase genes and knockout mice [J].

Farese, RV .

CURRENT OPINION IN LIPIDOLOGY, 1998, 9 (02) :119-123

[4]

KINSELLA JE, 1990, AM J CLIN NUTR, V52, P1

[5]

KRAUSE BR, 1993, J LIPID RES, V34, P279

[6] INHIBITORS OF ACYL-COA-CHOLESTEROL ACYLTRANSFERASE .1. SYNTHESIS AND HYPOCHOLESTEROLEMIC ACTIVITY OF DIBENZ[B,E]OXEPIN-11-CARBOXANILIDES [J].

KUMAZAWA, T ;

YANASE, M ;

HARAKAWA, H ;

OBASE, H ;

SHIRAKURA, S ;

OHISHI, E ;

ODA, S ;

KUBO, K ;

YAMADA, K .

JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (06) :804-810

[7] Molecular cloning, functional expression and tissue distribution of rat acyl-coenzyme A:cholesterol acyltransferase [J].

Matsuda, H ;

Hakamata, H ;

Kawasaki, T ;

Sakashita, N ;

Miyazaki, A ;

Takahashi, K ;

Shichiri, M ;

Horiuchi, S .

BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM, 1998, 1391 (02) :193-203

[8] ACAT INHIBITORS AS ANTIATHEROSCLEROTIC AGENTS - COMPOUNDS AND MECHANISMS [J].

MATSUDA, K .

MEDICINAL RESEARCH REVIEWS, 1994, 14 (03) :271-305

[9] Disruption of the acyl-CoA:cholesterol acyltransferase gene in mice: Evidence suggesting multiple cholesterol esterification enzymes in mammals [J].

Meiner, VL ;

Cases, S ;

Myers, HM ;

Sande, ER ;

Bellosta, S ;

Schambelan, M ;

Pitas, RE ;

McGuire, J ;

Herz, J ;

Farese, RV .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (24) :14041-14046

[10] The hypolipidemic action of the ACAT inhibitor HL-004 in hamsters fed normal chow [J].

Murakami, S ;

Ohta, Y ;

Asami, Y ;

Yamagishi, I ;

Toda, Y ;

Sato, M ;

Tomisawa, K .

GENERAL PHARMACOLOGY, 1996, 27 (08) :1383-1386