Matches in SemOpenAlex for { <https://semopenalex.org/work/W2004594927> ?p ?o ?g. }
Showing items 1 to 94 of
94
with 100 items per page.
- W2004594927 endingPage "1523" @default.
- W2004594927 startingPage "1513" @default.
- W2004594927 abstract "Endothelin-1 is the most potent peptidic vasoconstrictor discovered to date. The final step of posttranslational processing of this peptide is the conversion of its precursor by endothelin-converting enzyme-1 (ECE-1), a metalloprotease which displays high amino acid sequence identity with neutral endopeptidase 24.11 (NEP) especially at the catalytic center. A series of potent and selective arylacetylene-containing ECE-1 inhibitors have been prepared. (S,S)-3-Cyclohexyl-2-[[5-(2,4-difluorophenyl)-2-[(phosphonomethyl)amino]pent-4-ynoyl]amino]propionic acid (47), an arylacetylene amino phosphonate dipeptide, was found to inhibit ECE-1 and NEP with IC50 values of 14 nM and 2 μM, respectively. Similarly, (S)-[[1-[(2-biphenyl-4-ylethyl)carbamoyl]-4-(2-fluorophenyl)but-3-ynyl]amino]methyl]phosphonic acid (56), an arylacetylene amino phosphonate amide, had IC50's of 33 nM and 6.5 μM for ECE-1 and NEP, respectively. Slight modification of the aryl moiety was found to have dramatic effects on ECE-1/NEP selectivity. The 2-fluoro dipeptide analogue, (S,S)-2-[[5-(2-fluorophenyl)-2-[(phosphonomethyl)amino]pent-4-ynoyl]amino]-4-methylpentanoic acid (40), showed a 72-fold selectivity for ECE-1 over NEP, while the 3-fluoro dipeptide analogue, (S,S)-2-[[5-(3-fluorophenyl)-2-[(phosphonomethyl)amino]pent-4-ynoyl]amino]-4-methylpentanoic acid (22), was equipotent for ECE-1 and NEP. Several of these inhibitors were shown to be potent in blocking ET-1 production in vivo as demonstrated by the big ET-1-induced pressor response in rats. These potent inhibitors are the most selective for ECE-1 reported to date and are envisaged to have a variety of therapeutic applications." @default.
- W2004594927 created "2016-06-24" @default.
- W2004594927 creator A5006480894 @default.
- W2004594927 creator A5008609343 @default.
- W2004594927 creator A5012825132 @default.
- W2004594927 creator A5023777417 @default.
- W2004594927 creator A5029571998 @default.
- W2004594927 creator A5045292582 @default.
- W2004594927 creator A5065799721 @default.
- W2004594927 creator A5073449379 @default.
- W2004594927 creator A5074065418 @default.
- W2004594927 creator A5077663312 @default.
- W2004594927 date "1998-04-01" @default.
- W2004594927 modified "2023-09-30" @default.
- W2004594927 title "Design and Synthesis of Potent, Selective Inhibitors of Endothelin-Converting Enzyme" @default.
- W2004594927 cites W1545907965 @default.
- W2004594927 cites W1895241692 @default.
- W2004594927 cites W1967051892 @default.
- W2004594927 cites W1970028957 @default.
- W2004594927 cites W1989968601 @default.
- W2004594927 cites W1995640200 @default.
- W2004594927 cites W2004151231 @default.
- W2004594927 cites W2011013688 @default.
- W2004594927 cites W2011693511 @default.
- W2004594927 cites W2022035094 @default.
- W2004594927 cites W2042879584 @default.
- W2004594927 cites W2047607813 @default.
- W2004594927 cites W2091828117 @default.
- W2004594927 cites W2092842648 @default.
- W2004594927 cites W2285606889 @default.
- W2004594927 cites W2951131630 @default.
- W2004594927 cites W2952722544 @default.
- W2004594927 cites W4237731454 @default.
- W2004594927 doi "https://doi.org/10.1021/jm970787c" @default.
- W2004594927 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9554884" @default.
- W2004594927 hasPublicationYear "1998" @default.
- W2004594927 type Work @default.
- W2004594927 sameAs 2004594927 @default.
- W2004594927 citedByCount "49" @default.
- W2004594927 countsByYear W20045949272013 @default.
- W2004594927 countsByYear W20045949272014 @default.
- W2004594927 countsByYear W20045949272015 @default.
- W2004594927 countsByYear W20045949272016 @default.
- W2004594927 countsByYear W20045949272017 @default.
- W2004594927 countsByYear W20045949272019 @default.
- W2004594927 countsByYear W20045949272020 @default.
- W2004594927 countsByYear W20045949272023 @default.
- W2004594927 crossrefType "journal-article" @default.
- W2004594927 hasAuthorship W2004594927A5006480894 @default.
- W2004594927 hasAuthorship W2004594927A5008609343 @default.
- W2004594927 hasAuthorship W2004594927A5012825132 @default.
- W2004594927 hasAuthorship W2004594927A5023777417 @default.
- W2004594927 hasAuthorship W2004594927A5029571998 @default.
- W2004594927 hasAuthorship W2004594927A5045292582 @default.
- W2004594927 hasAuthorship W2004594927A5065799721 @default.
- W2004594927 hasAuthorship W2004594927A5073449379 @default.
- W2004594927 hasAuthorship W2004594927A5074065418 @default.
- W2004594927 hasAuthorship W2004594927A5077663312 @default.
- W2004594927 hasConcept C185592680 @default.
- W2004594927 hasConcept C2777626080 @default.
- W2004594927 hasConcept C2779138802 @default.
- W2004594927 hasConcept C2779281246 @default.
- W2004594927 hasConcept C515207424 @default.
- W2004594927 hasConcept C55493867 @default.
- W2004594927 hasConcept C71240020 @default.
- W2004594927 hasConceptScore W2004594927C185592680 @default.
- W2004594927 hasConceptScore W2004594927C2777626080 @default.
- W2004594927 hasConceptScore W2004594927C2779138802 @default.
- W2004594927 hasConceptScore W2004594927C2779281246 @default.
- W2004594927 hasConceptScore W2004594927C515207424 @default.
- W2004594927 hasConceptScore W2004594927C55493867 @default.
- W2004594927 hasConceptScore W2004594927C71240020 @default.
- W2004594927 hasIssue "9" @default.
- W2004594927 hasLocation W20045949271 @default.
- W2004594927 hasLocation W20045949272 @default.
- W2004594927 hasOpenAccess W2004594927 @default.
- W2004594927 hasPrimaryLocation W20045949271 @default.
- W2004594927 hasRelatedWork W2008473455 @default.
- W2004594927 hasRelatedWork W2009273288 @default.
- W2004594927 hasRelatedWork W2047688858 @default.
- W2004594927 hasRelatedWork W2074988859 @default.
- W2004594927 hasRelatedWork W2097481889 @default.
- W2004594927 hasRelatedWork W2789704176 @default.
- W2004594927 hasRelatedWork W2949153590 @default.
- W2004594927 hasRelatedWork W2951494344 @default.
- W2004594927 hasRelatedWork W3185508373 @default.
- W2004594927 hasRelatedWork W2519877416 @default.
- W2004594927 hasVolume "41" @default.
- W2004594927 isParatext "false" @default.
- W2004594927 isRetracted "false" @default.
- W2004594927 magId "2004594927" @default.
- W2004594927 workType "article" @default.