FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2891135075> ?p ?o ?g. }

• W2891135075 endingPage "1855" @default.
• W2891135075 startingPage "1847" @default.
• W2891135075 abstract "Some quinoline-containing c-Met kinase inhibitors are aldehyde oxidase (AO) substrates. 3-Substituted quinoline triazolopyridine analogs were synthesized to understand the electron-donating and steric hindrance effects on AO-mediated metabolism. Metabolic stability studies for these quinoline analogs were carried out in liver cytosol from mice, rats, cynomolgus monkeys, and humans. Several 3-N–substituted analogs were found to be unstable in monkey liver cytosolic incubations (half-life, <10 minutes), and five of them (63, 53, 51, 11, and 71) were chosen for additional mechanistic studies. Mono-oxygenation on the quinoline ring was identified by liquid chromatography tandem mass spectrometry. Metabolite formation was inhibited by the AO inhibitors menadione and raloxifene, but not by the xanthine oxidase inhibitor allopurinol. It was found that small electron-donating groups at the 3-quinoline moiety made the analogs more susceptible to AO metabolism, whereas large 3-substituents could reverse the trend. Although species differences were observed, this trend was applicable to all species tested. Small electron-donating substituents at the 3-quinoline moiety increased both affinity (decreased Michaelis constant) and <i>V</i>_max maximum velocity toward AO in kinetic studies, whereas large substituents decreased both parameters probably as a result of steric hindrance. Based on our analysis, a common structural feature with high AO liability was proposed. Our finding could provide useful information for chemists to minimize potential AO liability when designing quinoline analogs." @default.
• W2891135075 created "2018-09-27" @default.
• W2891135075 creator A5010266153 @default.
• W2891135075 creator A5036759944 @default.
• W2891135075 creator A5064560621 @default.
• W2891135075 creator A5072513253 @default.
• W2891135075 creator A5084434322 @default.
• W2891135075 date "2018-09-12" @default.
• W2891135075 modified "2023-10-03" @default.
• W2891135075 title "Metabolism of c-Met Kinase Inhibitors Containing Quinoline by Aldehyde Oxidase, Electron Donating, and Steric Hindrance Effect" @default.
• W2891135075 cites W1489147212 @default.
• W2891135075 cites W1986811179 @default.
• W2891135075 cites W1992031126 @default.
• W2891135075 cites W2012209374 @default.
• W2891135075 cites W2023589339 @default.
• W2891135075 cites W2048949364 @default.
• W2891135075 cites W2058342217 @default.
• W2891135075 cites W2073597573 @default.
• W2891135075 cites W2073863010 @default.
• W2891135075 cites W2091094760 @default.
• W2891135075 cites W2107723834 @default.
• W2891135075 cites W2114112097 @default.
• W2891135075 cites W2118666253 @default.
• W2891135075 cites W2119432174 @default.
• W2891135075 cites W2120931971 @default.
• W2891135075 cites W2130647693 @default.
• W2891135075 cites W2132129561 @default.
• W2891135075 cites W2142198771 @default.
• W2891135075 cites W2156944722 @default.
• W2891135075 cites W2233464627 @default.
• W2891135075 cites W2315921289 @default.
• W2891135075 cites W2318573979 @default.
• W2891135075 cites W2327451947 @default.
• W2891135075 cites W2328212946 @default.
• W2891135075 cites W2514112267 @default.
• W2891135075 cites W2593129097 @default.
• W2891135075 cites W2604139305 @default.
• W2891135075 cites W2605332436 @default.
• W2891135075 cites W2746820070 @default.
• W2891135075 cites W2771257540 @default.
• W2891135075 cites W2796070144 @default.
• W2891135075 doi "https://doi.org/10.1124/dmd.118.081919" @default.
• W2891135075 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30209037" @default.
• W2891135075 hasPublicationYear "2018" @default.
• W2891135075 type Work @default.
• W2891135075 sameAs 2891135075 @default.
• W2891135075 citedByCount "17" @default.
• W2891135075 countsByYear W28911350752019 @default.
• W2891135075 countsByYear W28911350752020 @default.
• W2891135075 countsByYear W28911350752021 @default.
• W2891135075 countsByYear W28911350752022 @default.
• W2891135075 countsByYear W28911350752023 @default.
• W2891135075 crossrefType "journal-article" @default.
• W2891135075 hasAuthorship W2891135075A5010266153 @default.
• W2891135075 hasAuthorship W2891135075A5036759944 @default.
• W2891135075 hasAuthorship W2891135075A5064560621 @default.
• W2891135075 hasAuthorship W2891135075A5072513253 @default.
• W2891135075 hasAuthorship W2891135075A5084434322 @default.
• W2891135075 hasBestOaLocation W28911350751 @default.
• W2891135075 hasConcept C178790620 @default.
• W2891135075 hasConcept C181199279 @default.
• W2891135075 hasConcept C185592680 @default.
• W2891135075 hasConcept C201194858 @default.
• W2891135075 hasConcept C2776309666 @default.
• W2891135075 hasConcept C2776568683 @default.
• W2891135075 hasConcept C2777477808 @default.
• W2891135075 hasConcept C2778102346 @default.
• W2891135075 hasConcept C2779840689 @default.
• W2891135075 hasConcept C55493867 @default.
• W2891135075 hasConcept C71240020 @default.
• W2891135075 hasConceptScore W2891135075C178790620 @default.
• W2891135075 hasConceptScore W2891135075C181199279 @default.
• W2891135075 hasConceptScore W2891135075C185592680 @default.
• W2891135075 hasConceptScore W2891135075C201194858 @default.
• W2891135075 hasConceptScore W2891135075C2776309666 @default.
• W2891135075 hasConceptScore W2891135075C2776568683 @default.
• W2891135075 hasConceptScore W2891135075C2777477808 @default.
• W2891135075 hasConceptScore W2891135075C2778102346 @default.
• W2891135075 hasConceptScore W2891135075C2779840689 @default.
• W2891135075 hasConceptScore W2891135075C55493867 @default.
• W2891135075 hasConceptScore W2891135075C71240020 @default.
• W2891135075 hasIssue "12" @default.
• W2891135075 hasLocation W28911350751 @default.
• W2891135075 hasLocation W28911350752 @default.
• W2891135075 hasOpenAccess W2891135075 @default.
• W2891135075 hasPrimaryLocation W28911350751 @default.
• W2891135075 hasRelatedWork W1977241997 @default.
• W2891135075 hasRelatedWork W1982450728 @default.
• W2891135075 hasRelatedWork W2030067016 @default.
• W2891135075 hasRelatedWork W2035149549 @default.
• W2891135075 hasRelatedWork W2039483887 @default.
• W2891135075 hasRelatedWork W2050501218 @default.
• W2891135075 hasRelatedWork W2127000772 @default.
• W2891135075 hasRelatedWork W2950651423 @default.
• W2891135075 hasRelatedWork W2952072666 @default.
• W2891135075 hasRelatedWork W181344459 @default.
• W2891135075 hasVolume "46" @default.
• W2891135075 isParatext "false" @default.

• next