FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2895065338> ?p ?o ?g. }

• W2895065338 endingPage "48" @default.
• W2895065338 startingPage "37" @default.
• W2895065338 abstract "A series of novel pyridine-substituted piperidine derivatives were discovered as low nanomolar Ls-AChBP ligands with α7 nAChR partial agonism or antagonism activities. A high-resolution antagonist-bound Ls-AChBP complex was successfully resolved with a classic Loop C opening phenomenon and unique sulfur-π interactions which deviated from our previous docking mode to a large extent. With the knowledge of the co-complex, 27 novel piperidine derivatives were designed and synthesized. The structure-activity relationships (SARs) of the aromatic and pyridine regions were well established and binding modes were illustrated with the help of molecular docking which indicated that interactions with Trp 143 and the “water bridge” are essential for the high binding affinities. Halogen bonding as well as the space around 5′- or 6′- position of the pyridine ring was also proposed to influence the binding conformation of the compounds. Notably, two enantiomers of compound 2 showed opposite functions toward α7 nAChR and compound (S)-2 showed sub-nanomolar affinity (Ki = 0.86 nM) on Ls-AChBP and partial agonism (pEC50 = 4.69 ± 0.11,Emax = 36.1%) on α7 nAChR with reasonable pharmacokinetics (PK) properties and fine ability of blood-brain-barrier (BBB) penetration. This study provided promising hits to develop candidates targeting nAChR-related CNS diseases." @default.
• W2895065338 created "2018-10-12" @default.
• W2895065338 creator A5000432967 @default.
• W2895065338 creator A5001054661 @default.
• W2895065338 creator A5003856071 @default.
• W2895065338 creator A5008978214 @default.
• W2895065338 creator A5013456838 @default.
• W2895065338 creator A5015728065 @default.
• W2895065338 creator A5019891864 @default.
• W2895065338 creator A5022499603 @default.
• W2895065338 creator A5031156888 @default.
• W2895065338 creator A5032295514 @default.
• W2895065338 creator A5040391223 @default.
• W2895065338 creator A5049873519 @default.
• W2895065338 creator A5050672997 @default.
• W2895065338 creator A5063944023 @default.
• W2895065338 creator A5079024647 @default.
• W2895065338 creator A5079924199 @default.
• W2895065338 creator A5084161145 @default.
• W2895065338 date "2018-12-01" @default.
• W2895065338 modified "2023-10-12" @default.
• W2895065338 title "Discovery, cocrystallization and biological evaluation of novel piperidine derivatives as high affinity Ls-AChBP ligands possessing α7 nAChR activities" @default.
• W2895065338 cites W1447565288 @default.
• W2895065338 cites W1502233726 @default.
• W2895065338 cites W1539796472 @default.
• W2895065338 cites W1568332152 @default.
• W2895065338 cites W1865643442 @default.
• W2895065338 cites W1935354256 @default.
• W2895065338 cites W1969095345 @default.
• W2895065338 cites W1975118796 @default.
• W2895065338 cites W1990818258 @default.
• W2895065338 cites W2006425659 @default.
• W2895065338 cites W2009428104 @default.
• W2895065338 cites W2010022125 @default.
• W2895065338 cites W2010752451 @default.
• W2895065338 cites W2015971354 @default.
• W2895065338 cites W2016797595 @default.
• W2895065338 cites W2033083825 @default.
• W2895065338 cites W2034292442 @default.
• W2895065338 cites W2045776462 @default.
• W2895065338 cites W2049592631 @default.
• W2895065338 cites W2052323648 @default.
• W2895065338 cites W2056268811 @default.
• W2895065338 cites W2060488758 @default.
• W2895065338 cites W2064221775 @default.
• W2895065338 cites W2066193597 @default.
• W2895065338 cites W2068516782 @default.
• W2895065338 cites W2071608242 @default.
• W2895065338 cites W2076063811 @default.
• W2895065338 cites W2082044483 @default.
• W2895065338 cites W2082242341 @default.
• W2895065338 cites W2093542942 @default.
• W2895065338 cites W2097345469 @default.
• W2895065338 cites W2120584765 @default.
• W2895065338 cites W2125200874 @default.
• W2895065338 cites W2128845098 @default.
• W2895065338 cites W2141246891 @default.
• W2895065338 cites W2146608786 @default.
• W2895065338 cites W2148677994 @default.
• W2895065338 cites W2164004007 @default.
• W2895065338 cites W2169051367 @default.
• W2895065338 cites W2178504779 @default.
• W2895065338 cites W2187857211 @default.
• W2895065338 cites W2194028553 @default.
• W2895065338 cites W2337882792 @default.
• W2895065338 cites W2418421815 @default.
• W2895065338 cites W2539097406 @default.
• W2895065338 cites W2560558729 @default.
• W2895065338 cites W2725119232 @default.
• W2895065338 cites W2738907897 @default.
• W2895065338 cites W2951178485 @default.
• W2895065338 cites W323852231 @default.
• W2895065338 doi "https://doi.org/10.1016/j.ejmech.2018.09.073" @default.
• W2895065338 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30317024" @default.
• W2895065338 hasPublicationYear "2018" @default.
• W2895065338 type Work @default.
• W2895065338 sameAs 2895065338 @default.
• W2895065338 citedByCount "1" @default.
• W2895065338 countsByYear W28950653382023 @default.
• W2895065338 crossrefType "journal-article" @default.
• W2895065338 hasAuthorship W2895065338A5000432967 @default.
• W2895065338 hasAuthorship W2895065338A5001054661 @default.
• W2895065338 hasAuthorship W2895065338A5003856071 @default.
• W2895065338 hasAuthorship W2895065338A5008978214 @default.
• W2895065338 hasAuthorship W2895065338A5013456838 @default.
• W2895065338 hasAuthorship W2895065338A5015728065 @default.
• W2895065338 hasAuthorship W2895065338A5019891864 @default.
• W2895065338 hasAuthorship W2895065338A5022499603 @default.
• W2895065338 hasAuthorship W2895065338A5031156888 @default.
• W2895065338 hasAuthorship W2895065338A5032295514 @default.
• W2895065338 hasAuthorship W2895065338A5040391223 @default.
• W2895065338 hasAuthorship W2895065338A5049873519 @default.
• W2895065338 hasAuthorship W2895065338A5050672997 @default.
• W2895065338 hasAuthorship W2895065338A5063944023 @default.
• W2895065338 hasAuthorship W2895065338A5079024647 @default.
• W2895065338 hasAuthorship W2895065338A5079924199 @default.
• W2895065338 hasAuthorship W2895065338A5084161145 @default.
• W2895065338 hasConcept C155647269 @default.

• next