Linked Life Data

11428921

Source:http://linkedlifedata.com/resource/pubmed/id/11428921

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2001-6-28
pubmed:abstractText
This paper describes the synthesis and physical and biological effects of introducing different substituents at the alpha-position of the tryptophan containing neurokinin-1 receptor antagonist [(R)-2-(1H-indol-3-yl)-1-methyl-1-((S)-1-phenyl-ethylcarbamoyl)-ethyl]-carbamic acid benzofuran-2-ylmethyl ester (CI 1021). The described compounds all exhibit less than 5 nM binding affinities for the human neurokinin-1 receptor and selectivity over the tachykinin NK(2) and NK(3) receptor subtypes. Application of variable temperature nuclear magnetic resonance spectroscopy studies of the amide and urethane protons was utilized to determine the existence of an intramolecular hydrogen bond. This intramolecular hydrogen bond increases the apparent lipophilicity to allow increased central nervous system penetration and pharmacological activity (gerbil foot tap test) in the case of the highest affinity compound [(S)-1-dimethylaminomethyl-2-(1H-indol-3-yl)-1-((S)-1-phenyl-ethylcarbamoyl)-ethyl]-carbamic acid benzofuran-2-ylmethyl ester (PD 174424) over those analogues that could not form an intramolecular hydrogen bond.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2276-85
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Utilization of an intramolecular hydrogen bond to increase the CNS penetration of an NK(1) receptor antagonist.
pubmed:affiliation
Pfizer Global Research and Development, Cambridge University Forvie Site, Robinson Way, Cambridge CB2 2QB, UK.
pubmed:publicationType
Journal Article