|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
12
|
|
pubmed:dateCreated |
2007-6-4
|
|
pubmed:abstractText |
Based on X-ray crystallographic data of complexes of chlorodysinosin A with the enzyme thrombin, a series of analogs were synthesized varying the nature of the P(1), P(2), and P(3) pharmacophoric sites and the central octahydroindole carboxyamide core. In general, introduction of a hydrophobic substituent on the d-leucine amide residue dramatically improved the inhibition of the enzyme. This is rationalized based on a better fit of the P(3) subunit in the hydrophobic S(3) enzyme site. Single digit nanomolar inhibition expressed as IC(50) was observed for several analogs.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jun
|
|
pubmed:issn |
0960-894X
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
15
|
|
pubmed:volume |
17
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
3480-5
|
|
pubmed:dateRevised |
2010-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:17428662-Amides,
pubmed-meshheading:17428662-Antithrombins,
pubmed-meshheading:17428662-Crystallography, X-Ray,
pubmed-meshheading:17428662-Hydrophobic and Hydrophilic Interactions,
pubmed-meshheading:17428662-Indoles,
pubmed-meshheading:17428662-Inhibitory Concentration 50,
pubmed-meshheading:17428662-Leucine,
pubmed-meshheading:17428662-Models, Chemical,
pubmed-meshheading:17428662-Oligopeptides,
pubmed-meshheading:17428662-Structure-Activity Relationship,
pubmed-meshheading:17428662-Thrombin
|
|
pubmed:year |
2007
|
|
pubmed:articleTitle |
Structure-based organic synthesis of unnatural aeruginosin hybrids as potent inhibitors of thrombin.
|
|
pubmed:affiliation |
Department of Chemistry, Université de Montréal, PO Box 6128, Station, Centre-Ville, Montréal, QC, Canada H3C 3J7. Stephen.hanessian@umontreal.ca
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
