Linked Life Data

8536341

Source:http://linkedlifedata.com/resource/pubmed/id/8536341

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1996-2-8
pubmed:abstractText
Three new lactam-conformationally restricted arginine derivatives, 1-butyl-3-(6,7-dimethoxy-2-naphthylsulfonyl)-3-(3-guanidinoprop yl)-substituted gamma-, delta-, and epsilon-lactams (2-4), were synthesized on the basis of backbone modification of the lead structure, 6,7-dimethoxy-2-naphthylsulfonylarginine n-butylmethylamide (1). We tested these compounds for inhibitory activity toward thrombin and other trypsin-like enzymes (trypsin, factor Xa, plasmin, and kallikrein). All the compounds synthesized (1-4) potently inhibited thrombin with IC50 values of 0.75, 0.70, 0.92, and 3.2 microM, respectively; they inhibited thrombin over 40-fold more effectively than the other enzymes tested. The gamma-lactam (2) with the most profound inhibitory activity toward thrombin was a reversible inhibitor with a Ki of 0.26 microM. Compound 2 also showed better thrombin selectivity than the lead compound (1). The lactam-conformational restriction of arylsulfonylarginine amides, especially gamma-lactam, has thus proved to be a useful device for the improvement of antithrombotic activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0009-2363
pubmed:author
pubmed:issnType
Print
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1683-91
pubmed:dateRevised
2000-12-18
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Lactam-conformationally restricted analogs of N alpha-arylsulfonyl arginine amide: design, synthesis and inhibitory activity toward thrombin and related enzymes.
pubmed:affiliation
Research Institute, Fuji Chemical Industries, Ltd, Toyama, Japan.
pubmed:publicationType
Journal Article