Linked Life Data

9784116

Source:http://linkedlifedata.com/resource/pubmed/id/9784116

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
1998-11-23
pubmed:abstractText
A series of N-alkyl-N-[(fluorophenoxy)benzyl]-N'-arylureas were prepared and evaluated for their ability to inhibit intestinal acyl-CoA:cholesterol O-acyltransferase and to inhibit accumulation of cholesteryl esters in macrophages in vitro. In vivo hypocholesterolemic activity was assessed in cholesterol-fed rats by oral administration as a dietary admixture and/or by gavage in a PEG400 vehicle. Modification of the alkyl substituent on the N'-aryl moiety and on the urea nitrogen significantly influenced macrophage assay in vitro. Toxicological study revealed a distinct relationship between macrophage assay and the toxicity observed in adrenal glands of rabbits treated with representatives of this series of compounds. Investigations utilizing the macrophage assay as an indicator for adrenal toxicity led to the identification of compounds 1g (FR190809) and 1k (FR186485, or FR195249 as its hydrochloride salt) as potent, nonadrenotoxic, orally efficacious ACAT inhibitors irrespective of the administration method.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4408-20
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Inhibitors of acyl-CoA:cholesterol O-acyltransferase. 3. Discovery of a novel series of N-alkyl-N-[(fluorophenoxy)benzyl]-N'-arylureas with weak toxicological effects on adrenal glands.
pubmed:affiliation
Medicinal Chemistry Research Laboratories, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Company Ltd., 2-1-6 Kashima, Yodogawa-ku, Osaka 532-8514, Japan.
pubmed:publicationType
Journal Article, In Vitro