FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2950308927> ?p ?o ?g. }

• W2950308927 endingPage "3631" @default.
• W2950308927 startingPage "3622" @default.
• W2950308927 abstract "Twenty-three new derivatives of sulfaphenazole (SPA) were synthesized to further explore the topology of the active sites of human liver cytochromes P450 of the 2C subfamily and to find new selective inhibitors of these cytochromes. These compounds are derived from SPA by replacement of the NH(2) and H (of the SO(2)NH function) substituents of SPA with various R(1) and R(2) groups, respectively. Their inhibitory effects were studied on recombinant CYP 2C8, 2C9, 2C18, and 2C19 expressed in yeast. High affinities for CYP 2C9 (IC(50) < 1 microM) were only observed for SPA derivatives having the SO(2)NH function and a relatively small R(1) substituent (R(1) = NH(2), CH(3)). Any increase in the size of R(1) led to a moderate decrease of the affinity, and the N-alkylation of the SO(2)NH function of SPA to a greater decrease of this affinity. The same structural changes led to opposite effects on molecular recognition by CYP 2C8 and 2C18, which generally exhibited similar behaviors. Thus, contrary to CYP 2C9, CYP 2C8 and 2C18 generally prefer neutral compounds with relatively large R(1) and R(2) substituents. CYP 2C19 showed an even lower affinity for anionic compounds than CYP 2C8 and 2C18. However, as CYP 2C8 and 2C18, CYP 2C19 showed a much better affinity for neutral compounds derived from N-alkylation of SPA and for anionic compounds bearing a larger R(1) substituent. One of the new compounds (R(1) = methyl, R(2) = propyl) inhibited all human CYP 2Cs with IC(50) values between 10 and 20 microM, while another one (R(1) = allyl, R(2) = methyl) inhibited all CYP 2Cs except CYP 2C9, and a third one (R(1) = R(2) = methyl) inhibited all CYP 2Cs except CYP 2C8. Only 2 compounds of the 25 tested derivatives were highly selective toward one human CYP 2C; these are SPA and compound 1 (R(1) = CH(3), R(2) = H), which acted as selective CYP 2C9 inhibitors. However, some SPA derivatives selectively inhibited CYP 2C8 and 2C18. Since CYP 2C18 is hardly detectable in human liver, these derivatives could be interesting molecules to selectively inhibit CYP 2C8 in human liver microsomes. Thus, compound 11 (R(1) = NH(2), R(2) = (CH(2))(2)CH(CH(3))(2)) appears to be particularly interesting for that purpose as its IC(50) value for CYP 2C8 is low (3 microM) and 20-fold smaller than those found for CYP 2C9 and 2C19." @default.
• W2950308927 created "2019-06-27" @default.
• W2950308927 creator A5000449092 @default.
• W2950308927 creator A5017663660 @default.
• W2950308927 creator A5025256836 @default.
• W2950308927 creator A5026084893 @default.
• W2950308927 creator A5050418511 @default.
• W2950308927 creator A5067942243 @default.
• W2950308927 date "2001-09-08" @default.
• W2950308927 modified "2023-10-18" @default.
• W2950308927 title "Synthesis of Sulfaphenazole Derivatives and Their Use as Inhibitors and Tools for Comparing the Active Sites of Human Liver Cytochromes P450 of the 2C Subfamily" @default.
• W2950308927 cites W1498118152 @default.
• W2950308927 cites W1508115080 @default.
• W2950308927 cites W1515404266 @default.
• W2950308927 cites W1532212858 @default.
• W2950308927 cites W1543823041 @default.
• W2950308927 cites W1567686906 @default.
• W2950308927 cites W1690359427 @default.
• W2950308927 cites W1775749144 @default.
• W2950308927 cites W1789048542 @default.
• W2950308927 cites W1900675426 @default.
• W2950308927 cites W1971826768 @default.
• W2950308927 cites W1972453313 @default.
• W2950308927 cites W1985570876 @default.
• W2950308927 cites W1995947485 @default.
• W2950308927 cites W2008984280 @default.
• W2950308927 cites W2011826075 @default.
• W2950308927 cites W2057467439 @default.
• W2950308927 cites W2068547598 @default.
• W2950308927 cites W2083833752 @default.
• W2950308927 cites W2094553915 @default.
• W2950308927 cites W2167082309 @default.
• W2950308927 cites W2192742478 @default.
• W2950308927 cites W2949420462 @default.
• W2950308927 cites W994970986 @default.
• W2950308927 doi "https://doi.org/10.1021/jm010861y" @default.
• W2950308927 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11606127" @default.
• W2950308927 hasPublicationYear "2001" @default.
• W2950308927 type Work @default.
• W2950308927 sameAs 2950308927 @default.
• W2950308927 citedByCount "26" @default.
• W2950308927 countsByYear W29503089272012 @default.
• W2950308927 countsByYear W29503089272013 @default.
• W2950308927 countsByYear W29503089272015 @default.
• W2950308927 countsByYear W29503089272018 @default.
• W2950308927 countsByYear W29503089272019 @default.
• W2950308927 countsByYear W29503089272021 @default.
• W2950308927 countsByYear W29503089272022 @default.
• W2950308927 countsByYear W29503089272023 @default.
• W2950308927 crossrefType "journal-article" @default.
• W2950308927 hasAuthorship W2950308927A5000449092 @default.
• W2950308927 hasAuthorship W2950308927A5017663660 @default.
• W2950308927 hasAuthorship W2950308927A5025256836 @default.
• W2950308927 hasAuthorship W2950308927A5026084893 @default.
• W2950308927 hasAuthorship W2950308927A5050418511 @default.
• W2950308927 hasAuthorship W2950308927A5067942243 @default.
• W2950308927 hasConcept C104317684 @default.
• W2950308927 hasConcept C161790260 @default.
• W2950308927 hasConcept C164361826 @default.
• W2950308927 hasConcept C181199279 @default.
• W2950308927 hasConcept C185592680 @default.
• W2950308927 hasConcept C2778689049 @default.
• W2950308927 hasConcept C2780283098 @default.
• W2950308927 hasConcept C41183919 @default.
• W2950308927 hasConcept C50929876 @default.
• W2950308927 hasConcept C55493867 @default.
• W2950308927 hasConcept C71240020 @default.
• W2950308927 hasConceptScore W2950308927C104317684 @default.
• W2950308927 hasConceptScore W2950308927C161790260 @default.
• W2950308927 hasConceptScore W2950308927C164361826 @default.
• W2950308927 hasConceptScore W2950308927C181199279 @default.
• W2950308927 hasConceptScore W2950308927C185592680 @default.
• W2950308927 hasConceptScore W2950308927C2778689049 @default.
• W2950308927 hasConceptScore W2950308927C2780283098 @default.
• W2950308927 hasConceptScore W2950308927C41183919 @default.
• W2950308927 hasConceptScore W2950308927C50929876 @default.
• W2950308927 hasConceptScore W2950308927C55493867 @default.
• W2950308927 hasConceptScore W2950308927C71240020 @default.
• W2950308927 hasIssue "22" @default.
• W2950308927 hasLocation W29503089271 @default.
• W2950308927 hasLocation W29503089272 @default.
• W2950308927 hasOpenAccess W2950308927 @default.
• W2950308927 hasPrimaryLocation W29503089271 @default.
• W2950308927 hasRelatedWork W1585263941 @default.
• W2950308927 hasRelatedWork W1966024327 @default.
• W2950308927 hasRelatedWork W1984949433 @default.
• W2950308927 hasRelatedWork W2115712439 @default.
• W2950308927 hasRelatedWork W2143619931 @default.
• W2950308927 hasRelatedWork W2152598442 @default.
• W2950308927 hasRelatedWork W2311228442 @default.
• W2950308927 hasRelatedWork W2523831781 @default.
• W2950308927 hasRelatedWork W3017862060 @default.
• W2950308927 hasRelatedWork W4241081643 @default.
• W2950308927 hasVolume "44" @default.
• W2950308927 isParatext "false" @default.
• W2950308927 isRetracted "false" @default.
• W2950308927 magId "2950308927" @default.
• W2950308927 workType "article" @default.