SYNTHESIS AND HYPOCHOLESTEROLEMIC ACTIVITY OF 6,7-DIHYDRO-4H-PYRAZOLO[1,5-A]PYRROLO[3,4-D]PYRIMIDINE-5,8-DIONES, NOVEL INHIBITORS OF ACYLCOA-CHOLESTEROL O-ACYLTRANSFERASE

被引：28

作者：

LARSEN, SD

SPILMAN, CH

BELL, FP

DINH, DM

MARTINBOROUGH, E

WILSON, GJ

机构：

[1] Metabolic Diseases Research, Upjohn Company, Kalamazoo

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1991年 / 34卷 / 05期

关键词：

D O I：

10.1021/jm00109a028

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of 6,7-dihydro-4H-pyrazolo[1,5-a]pyrrolo[3,4-d]pyrimidine-5,8-dione inhibitors of the enzyme acyl-CoA:cholesterol O-acyltransferase is described. A number of these derivatives were found to be potent modulators of serum lipoprotein levels in cholesterol-fed rats. Further evaluation of one of the most effective analogues confirmed that it was significantly blocking the absorption of cholesterol from the gut.

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页码：1721 / 1727

页数：7

相关论文

共 35 条

[1] SYNTHESIS + MUSCLE RELAXANT PROPERTIES OF 3-AMINO-4-ARYLPYRAZOLES [J].

ANDERSON, EL ;

GREENE, LC ;

REIFF, HE ;

LAFFERTY, JJ ;

CASEY, JE .

JOURNAL OF MEDICINAL CHEMISTRY, 1964, 7 (03) :259-&

[2]

AUZZI G, 1978, FARMACO-ED SCI, V33, P14

[3] THE EFFECT OF LIDOCAINE ON CHOLESTEROL INFLUX, ESTERIFICATION, AND ACCUMULATION IN CULTURED-CELLS [J].

BELL, FP ;

ROTHBLAT, GH ;

BAMBERGER, M .

CANADIAN JOURNAL OF BIOCHEMISTRY, 1982, 60 (10) :967-971

[4] CHLORPROMAZINE INHIBITS ARTERIAL ACAT AND REDUCES ARTERIAL CHOLESTEROL AND CHOLESTERYL ESTER ACCUMULATION IN CHOLESTEROL-FED RABBITS [J].

BELL, FP ;

SCHAUB, RG .

ARTERIOSCLEROSIS, 1986, 6 (01) :42-49

[5]

BELL FP, 1986, PHARM CONTROL HYPERL, P409

[6]

Checchi S., 1956, GAZZ CHIM ITAL, V86, P631

[7] POTENTIAL ANTIATHEROSCLEROTIC AGENTS .5. AN ACYL-COA - CHOLESTEROL O-ACYLTRANSFERASE INHIBITOR WITH HYPOCHOLESTEROLEMIC ACTIVITY [J].

DEVRIES, VG ;

SCHAFFER, SA ;

LARGIS, EE ;

DUTIA, MD ;

WANG, CH ;

BLOOM, JD ;

KATOCS, AS .

JOURNAL OF MEDICINAL CHEMISTRY, 1986, 29 (07) :1131-1133

[8] POTENTIAL ANTIATHEROSCLEROTIC AGENTS .6. HYPOCHOLESTEROLEMIC TRISUBSTITUTED UREA ANALOGS [J].

DEVRIES, VG ;

BLOOM, JD ;

DUTIA, MD ;

KATOCS, AS ;

LARGIS, EE .

JOURNAL OF MEDICINAL CHEMISTRY, 1989, 32 (10) :2318-2325

[9]

Dymek W, 1966, Acta Pol Pharm, V23, P207

[10]

HEIDER JG, 1983, J LIPID RES, V24, P1127

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