Linked Life Data

19046881

Source:http://linkedlifedata.com/resource/pubmed/id/19046881

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-12-26
pubmed:abstractText
We previously disclosed a series of highly potent FXa inhibitors bearing alpha-substituted (CH(2)NR(1)R(2)) phenylcyclopropyl P4 moieties in the pyrazolodihydropyridone core system. Herein, we describe our continuous SAR efforts in this series. Effects of the C-3 substitution of the pyrazolodihydropyridone core and the alpha-substitution (R group) of the cyclopropyl ring on FXa binding affinity (FXa K(i)), human plasma anticoagulant activity (PT EC(2x)) and permeability are discussed. A set of compounds obtained from optimization of the R group and the C-3 substituent were orally bioavailable in dogs. Furthermore, representative compounds were highly efficacious in the rabbit arterio-venous shunt thrombosis model (EC(50)s=29-81nM).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1464-3405
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
462-8
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Highly efficacious factor Xa inhibitors containing alpha-substituted phenylcycloalkyl P4 moieties.
pubmed:affiliation
Research and Discovery, Bristol-Myers Squibb Company, P.O. Box 5400, Princeton, NJ 08543-5400, USA. jennifer.qiao@bms.com
pubmed:publicationType
Journal Article