Linked Life Data

8149456

Source:http://linkedlifedata.com/resource/pubmed/id/8149456

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1994-5-11
pubmed:abstractText
The design, synthesis and structure-activity relationships of transition-state inhibitors containing the dihydroxyethylene isostere at the scissile site are described. The compounds with (2S,3R,4S)-4-amino-5-cyclohexyl-1-morpholino-2,3-pentanediol at the P1-P1 site are potent renin inhibitors. (2S,3R,4S)-4-[N-[(2S)-3-Ethylsulfonyl-2-(1-naphthylmethyl)propiony l]-L- norleucyl]amino-5-cyclohexyl-1-morpholino-2,3-pentanediol (2) (BW-175), which is the most potent inhibitor (IC50: 3.3 nM against human renin) in this series, poorly inhibits cathepsin D (IC50: 26000 nM) and pepsin (IC50: > 100000 nM), and thus it is specific for renin. Compound 2 contains only one amino acid and showed an oral bioavailability of 2.8% at 10 mg/kg and 9.7% at 30 mg/kg in rats. The interaction between renin and inhibitor 2 is discussed on the basis of molecular modeling studies.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0009-2363
pubmed:author
pubmed:issnType
Print
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
306-13
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Renin inhibitors. III. Synthesis and structure-activity relationships of transition-state inhibitors containing dihydroxyethylene isostere at the P1-P1 site.
pubmed:affiliation
Structural Biology & Chemistry, Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Ibaraki, Japan.
pubmed:publicationType
Journal Article