FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4281388081> ?p ?o ?g. }

• W4281388081 abstract "Tricyclic tetrahydrooxazolo[4,5-h]-[3]benzazepin-9-ols 22 were designed as phenol bioisosteres of tetrahydro-3-benzazepine-1,7-diols. Key features of the synthesis are the introduction of the trifluoromethylsulfonyl and allyl protective groups at the heterocyclic N-atoms. Two methods were developed to convert the triflyl-protected ketone 16 into tricyclic alcohols 21 bearing various N-substituents. According to the first method, trifluoromethanesulfinate was removed by K2 CO3 . Following the selective reduction of the imino moiety of 17 with NaBH(OAc)3 afforded the aminoketone 18, which was reductively alkylated and reduced. According to the second method, both the imine and the ketone of the iminoketone 17 were reduced with NaBH4 to yield the aminoalcohol 20, which was alkylated or reductively alkylated to form tertiary amines 21f-21r. In the last step, the allyl protective group of 21 was removed with RhCl3 and HCl to obtain oxazolones 22. In receptor binding studies using [3 H]ifenprodil as radioligand ketone, 22m showed the highest GluN2B affinity (Ki = 88 nM). However, a reduced affinity toward GluN2B subunit-containing N-methyl- d-aspartate (NMDA) receptors was observed for oxazolones 22 compared to bioisosteric 3-benzazepine-1,7-diols. High selectivity of 22m for the ifenprodil binding site of GluN2B-NMDA receptors over the 1-(1-phenylcyclohexyl)piperidine binding site and σ2 receptors was observed, but only negligible selectivity over σ1 receptors. In two-electrode voltage clamp experiments, the 4-phenylbutyl derivative 22d (Ki = 422 nM) demonstrated 80% inhibition of ion flux at a concentration of 1 µM. The differences in GluN2B affinity and inhibitory activity are explained by docking studies. In conclusion, 22d is regarded as a novel scaffold of highly potent GluN1/GluN2B antagonists." @default.
• W4281388081 created "2022-05-25" @default.
• W4281388081 creator A5003084740 @default.
• W4281388081 creator A5015679062 @default.
• W4281388081 creator A5040260186 @default.
• W4281388081 creator A5046838535 @default.
• W4281388081 creator A5053327437 @default.
• W4281388081 creator A5061053817 @default.
• W4281388081 creator A5071739030 @default.
• W4281388081 date "2022-05-23" @default.
• W4281388081 modified "2023-09-29" @default.
• W4281388081 title "Phenol—Benzoxazolone bioisosteres: Synthesis and biological evaluation of tricyclic GluN2B‐selective <i>N</i>‐methyl‐<scp>d</scp>‐aspartate receptor antagonists" @default.
• W4281388081 cites W1499205986 @default.
• W4281388081 cites W1918693803 @default.
• W4281388081 cites W1966517040 @default.
• W4281388081 cites W1974718824 @default.
• W4281388081 cites W1978901759 @default.
• W4281388081 cites W1981907642 @default.
• W4281388081 cites W1994673500 @default.
• W4281388081 cites W2012641732 @default.
• W4281388081 cites W2015411250 @default.
• W4281388081 cites W2022133719 @default.
• W4281388081 cites W2024380057 @default.
• W4281388081 cites W2025302434 @default.
• W4281388081 cites W2037852973 @default.
• W4281388081 cites W2038090524 @default.
• W4281388081 cites W2039974695 @default.
• W4281388081 cites W2045651297 @default.
• W4281388081 cites W2053702542 @default.
• W4281388081 cites W2055862612 @default.
• W4281388081 cites W2057620319 @default.
• W4281388081 cites W2065771857 @default.
• W4281388081 cites W2074631079 @default.
• W4281388081 cites W2080980389 @default.
• W4281388081 cites W2086721196 @default.
• W4281388081 cites W2089094370 @default.
• W4281388081 cites W2100063864 @default.
• W4281388081 cites W2107339318 @default.
• W4281388081 cites W2108909652 @default.
• W4281388081 cites W2111117466 @default.
• W4281388081 cites W2116064503 @default.
• W4281388081 cites W2124134368 @default.
• W4281388081 cites W2125440566 @default.
• W4281388081 cites W2139976683 @default.
• W4281388081 cites W2205882274 @default.
• W4281388081 cites W2324507733 @default.
• W4281388081 cites W2594072479 @default.
• W4281388081 cites W2727496056 @default.
• W4281388081 cites W2739505366 @default.
• W4281388081 cites W2782108388 @default.
• W4281388081 cites W2805313681 @default.
• W4281388081 cites W2901034219 @default.
• W4281388081 cites W2913019761 @default.
• W4281388081 cites W2953278621 @default.
• W4281388081 cites W2984556569 @default.
• W4281388081 cites W3025135002 @default.
• W4281388081 cites W3120600822 @default.
• W4281388081 cites W4214738631 @default.
• W4281388081 doi "https://doi.org/10.1002/ardp.202200147" @default.
• W4281388081 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35606894" @default.
• W4281388081 hasPublicationYear "2022" @default.
• W4281388081 type Work @default.
• W4281388081 citedByCount "2" @default.
• W4281388081 countsByYear W42813880812022 @default.
• W4281388081 countsByYear W42813880812023 @default.
• W4281388081 crossrefType "journal-article" @default.
• W4281388081 hasAuthorship W4281388081A5003084740 @default.
• W4281388081 hasAuthorship W4281388081A5015679062 @default.
• W4281388081 hasAuthorship W4281388081A5040260186 @default.
• W4281388081 hasAuthorship W4281388081A5046838535 @default.
• W4281388081 hasAuthorship W4281388081A5053327437 @default.
• W4281388081 hasAuthorship W4281388081A5061053817 @default.
• W4281388081 hasAuthorship W4281388081A5071739030 @default.
• W4281388081 hasBestOaLocation W42813880811 @default.
• W4281388081 hasConcept C118792377 @default.
• W4281388081 hasConcept C155647269 @default.
• W4281388081 hasConcept C161790260 @default.
• W4281388081 hasConcept C164361826 @default.
• W4281388081 hasConcept C170493617 @default.
• W4281388081 hasConcept C178790620 @default.
• W4281388081 hasConcept C185592680 @default.
• W4281388081 hasConcept C2776568683 @default.
• W4281388081 hasConcept C2776573223 @default.
• W4281388081 hasConcept C2777738585 @default.
• W4281388081 hasConcept C2778498671 @default.
• W4281388081 hasConcept C2778851735 @default.
• W4281388081 hasConcept C2780376555 @default.
• W4281388081 hasConcept C2781132042 @default.
• W4281388081 hasConcept C55493867 @default.
• W4281388081 hasConcept C67018056 @default.
• W4281388081 hasConcept C67847695 @default.
• W4281388081 hasConcept C71240020 @default.
• W4281388081 hasConceptScore W4281388081C118792377 @default.
• W4281388081 hasConceptScore W4281388081C155647269 @default.
• W4281388081 hasConceptScore W4281388081C161790260 @default.
• W4281388081 hasConceptScore W4281388081C164361826 @default.
• W4281388081 hasConceptScore W4281388081C170493617 @default.
• W4281388081 hasConceptScore W4281388081C178790620 @default.
• W4281388081 hasConceptScore W4281388081C185592680 @default.
• W4281388081 hasConceptScore W4281388081C2776568683 @default.

• next