Linked Life Data

1548684

Source:http://linkedlifedata.com/resource/pubmed/id/1548684

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1992-4-17
pubmed:abstractText
In a preliminary communication (J. Med. Chem. 1989, 32, 11-13) a series of perfluoro-N-[4-(1H-tetrazol-5ylmethyl)phenyl]alkana mides (perfluoro anilides I), designed as novel analogues of ciglitazone, were reported to possess oral antidiabetic activity in two genetic animal models of non-insulin-dependent diabetes mellitus (NIDDM): obese (ob/ob) and diabetic (db/db) mice. In this report, the results from a structure-activity relationship (SAR) study of the series I are described. Comprehensive statistical analysis among the 86 analogues screened for blood glucose lowering in ob/ob mice was achieved by a new application of a general statistical procedure which made it possible to make meaningful comparisons between more than 140 separate experiments (N = 2966). Perfluoro anilides I lowered plasma glucose in the hyperglycemic ob/ob and db/db mice but not in euglycemic normal rats. In the hyperinsulinemic ob/ob mouse, decreases in plasma insulin levels paralleled the decline in plasma glucose. Potency and efficacy in the series was shown to be dependent on the length of the perfluorocarbon chain (RF) of I. Optimal activity occurred with the C7 and C8 RF chains. The more extensive SAR studies reported here, indicated that the lipophilic RF chain is the most important structural element of I since neither the phenyl nor tetrazole rings present in anilides I were necessary for antihyperglycemic activity while medium length (C7-C8) RF chains, especially the C7F15 chain, were shown to confer antihyperglycemic activity in ob/ob mice to a wide variety of structures.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
944-53
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Perfluorocarbon-based antidiabetic agents.
pubmed:affiliation
Medicinal Chemistry Department, Wyeth-Ayerst Research, Princeton, New Jersey 08543-8000.
pubmed:publicationType
Journal Article, Comparative Study