Linked Life Data

19904934

Source:http://linkedlifedata.com/resource/pubmed/id/19904934

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-1-8
pubmed:abstractText
Human leukocyte elastase (HLE) is a serine protease stored in and secreted from neutrophils that plays a determinant role in the pathogenesis of several lung diseases. 4-Oxo-beta-lactams, previously reported as acylating agents of porcine pancreatic elastase, were found to be selective and potent inhibitors of HLE. Structure-activity relationship analysis showed that inhibitory activity is very sensitive to the nature of C-3 substituents, with small alkyl substituents such as a gem-diethyl group improving the inhibitory potency when compared to gem-methyl benzyl or ethyl benzyl counterparts. 4-Oxo-beta-lactams containing a heteroarylthiomethyl group on the para position of an N(1)-aryl moiety afforded highly potent and selective inhibition of HLE, even at a very low inhibitor to enzyme ratio, as shown by the k(on) value of 3.24 x 10(6) M(-1) s(-1) for 6f. The corresponding ortho isomers were 40- to 90-fold less potent.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1520-4804
pubmed:author
pubmed:issnType
Electronic
pubmed:day
14
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
241-53
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
4-Oxo-beta-lactams (azetidine-2,4-diones) are potent and selective inhibitors of human leukocyte elastase.
pubmed:affiliation
iMed.UL, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't