Linked Life Data

17933529

Source:http://linkedlifedata.com/resource/pubmed/id/17933529

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2007-11-6
pubmed:abstractText
A new series of pyrazole-based factor Xa inhibitors have been identified as part of our ongoing efforts to optimize previously reported clinical candidate razaxaban. Concern over the possible formation of primary aniline metabolites via amide hydrolysis led to the replacement of the primary amide linker between the pyrazole and phenyl moieties with secondary amides. This was accomplished by replacing the aniline with a variety of heterobicycles, of which indolines were the most potent. The indoline series demonstrated subnanomolar factor Xa binding K(i)s, modest to high selectivity versus other serine proteases, and good in vitro clotting activity. A small number of indoline fXa inhibitors were profiled in a dog pharmacokinetic model, one of which demonstrated pharmacokinetic parameters similar to that of clinical candidate razaxaban.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1464-3405
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6481-8
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Design, structure-activity relationship, and pharmacokinetic profile of pyrazole-based indoline factor Xa inhibitors.
pubmed:affiliation
Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400 Princeton, NJ 08542-5400, USA.
pubmed:publicationType
Journal Article, Comparative Study