Linked Life Data

7582985

Source:http://linkedlifedata.com/resource/pubmed/id/7582985

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1995-12-18
pubmed:abstractText
A series of 3-(3-guanidinopropyl)-azetidin-2-one derivatives was prepared and evaluated as inhibitors of cleavage of synthetic substrates in vitro by the serine proteases thrombin, trypsin and plasmin. The N-unsubstituted, 4-phenethyl derivative 9a demonstrated weak inhibition of these enzymes but acetylation of the beta-lactam N atom afforded 9b, an effective, time-dependent inhibitor of thrombin and a potent inhibitor of plasmin. Variation of the 4-position of the beta-lactam ring was examined in conjunction with different N-substituents to provide a series of potent, time-dependent inhibitors of thrombin. A C-4 substituent was essential for good inhibitory properties and, in general, polar C-4 substituents enhanced the selectivity of inhibition for thrombin compared to plasmin. A trans relationship between the C-4 and C-3 substituents was found to be superior to a cis disposition whilst homologation of the guanidinopropyl side chain to that of a guanidinobutyl moiety reduced activity. Several compounds were effective inhibitors of thrombin-induced clot formation in human plasma in vitro but activity in this assay did not correlate well with inhibition of thrombin-induced cleavage of a synthetic substrate, presumably a consequence of inherent chemical instability and degradation in plasma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0968-0896
pubmed:author
pubmed:issnType
Print
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1123-43
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Azetidin-2-one derivatives as inhibitors of thrombin.
pubmed:affiliation
Division of Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492-7660, USA.
pubmed:publicationType
Journal Article, Comparative Study