Linked Life Data

1433189

Source:http://linkedlifedata.com/resource/pubmed/id/1433189

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
1992-11-27
pubmed:abstractText
A thorough analysis of the mechanism of inhibition of human leukocyte elastase (HLE) by a monocyclic beta-lactam and the mechanism of beta-lactam hydrolysis led to the preparation of potent and highly stable inhibitors of HLE. This work led to the identification of 4-[(4-carboxyphenyl)-oxy]-3,3-diethyl-1- [[(phenylmethyl)amino]carbonyl]-2-azetidinone (2) as the first orally active inhibitor of human leukocyte elastase (HLE). Analogs of 2 with different substituents on the urea N were synthesized and evaluated for their activity in vitro against HLE as well as in vivo in a hamster lung hemorrhage model. Compounds with a methyl or a methoxy group in the para position of the benzene ring were very potent in both assays. The results are discussed on the basis of the proposed model for the binding of this class of inhibitors to HLE and a possible mechanism of inhibition is presented.
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
16
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
N
pubmed:pagination
3745-54
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Orally active beta-lactam inhibitors of human leukocyte elastase-1. Activity of 3,3-diethyl-2-azetidinones.
pubmed:affiliation
Department of Medicinal Chemical Research, Merck Research Laboratories, Rahway, New Jersey 07065.
pubmed:publicationType
Journal Article