Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-4-9
pubmed:abstractText
Direct inhibition of blood coagulation factors such as thrombin, factor VIIa, and factor Xa has shown great promise for treating thrombosis disorders. Inhibitors of these serine proteases have been designed, synthesized, and evaluated. Small molecule thrombin inhibitors typically contain P(1)-P(2)-P(3) components targeting the active binding site. Structure optimizations on the P(1) position and the P(3) position have been done extensively, but the P(2) position has not been as thoroughly studied as the other positions. Thrombin inhibitors with a rigid bicyclic P(2) unit are interesting compounds with a more defined conformation. Aeruginosins are a family of naturally occurring small molecules that exhibit serine protease inhibition activities; their structures are typically tetrapeptides with an unusual bicyclic amino acid core structure occupying the P(2) position. About 21 compounds sharing the same core structure have been isolated and identified so far, and their analogs have also been synthesized. In this review, the Structure Activity Relationship (SAR) of these compounds against thrombin and other serine proteases and their potential as antithrombotic agents will be discussed. The binding modes to thrombin and other factors of the coagulation cascade and the preparation of the aeruginosin core structure will be summarized. Besides the aeruginosin family, the SAR of other small molecule serine protease inhibitors with a rigid bicyclic P(2) unit will also be covered.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1875-6182
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
147-65
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Aeruginosin analogs and other compounds with rigid bicyclic structure as potential antithrombotic agents.
pubmed:affiliation
Department of Chemistry, University of New Orleans, New Orleans, LA 70148, USA. gwang2@uno.edu
pubmed:publicationType
Journal Article, Review