Matches in SemOpenAlex for { <https://semopenalex.org/work/W2953450003> ?p ?o ?g. }
- W2953450003 endingPage "2331" @default.
- W2953450003 startingPage "2331" @default.
- W2953450003 abstract "Glycogen synthase kinase-3β (GSK-3β) represents a relevant drug target for the treatment of neurodegenerative pathologies including Alzheimer’s disease. We herein report on the optimization of a novel class of GSK-3β inhibitors based on the tofacitinib-derived screen hit 3-((3R,4R)-3-((7-chloro-9H-pyrimido[4,5-b]indol-4-yl)(methyl)amino)-4-methylpiperidin-1-yl)-3-oxopropanenitrile (1). We synthesized a series of 19 novel 7-chloro-9H-pyrimido[4,5-b]indole-based derivatives and studied their structure–activity relationships with focus on the cyanoacetyl piperidine moiety. We unveiled the crucial role of the nitrile group and its importance for the activity of this compound series. A successful rigidization approach afforded 3-(3aRS,7aSR)-(1-(7-chloro-9H-pyrimido[4,5-b]indol-4-yl)octahydro-6H-pyrrolo[2,3-c]pyridin-6-yl)-propanenitrile (24), which displayed an IC50 value of 130 nM on GSK-3β and was further characterized by its metabolic stability. Finally, we disclosed the putative binding modes of the most potent inhibitors within the ATP binding site of GSK-3β by 1 µs molecular dynamics simulations." @default.
- W2953450003 created "2019-07-12" @default.
- W2953450003 creator A5010351902 @default.
- W2953450003 creator A5020943735 @default.
- W2953450003 creator A5029608207 @default.
- W2953450003 creator A5031324853 @default.
- W2953450003 creator A5035785939 @default.
- W2953450003 creator A5054574030 @default.
- W2953450003 creator A5082165691 @default.
- W2953450003 creator A5082294371 @default.
- W2953450003 date "2019-06-25" @default.
- W2953450003 modified "2023-10-01" @default.
- W2953450003 title "Design, Synthesis and Biological Evaluation of 7-Chloro-9H-pyrimido[4,5-b]indole-based Glycogen Synthase Kinase-3β Inhibitors" @default.
- W2953450003 cites W114839291 @default.
- W2953450003 cites W1496316111 @default.
- W2953450003 cites W1555947589 @default.
- W2953450003 cites W1972169338 @default.
- W2953450003 cites W1976499671 @default.
- W2953450003 cites W1978714931 @default.
- W2953450003 cites W1980456750 @default.
- W2953450003 cites W1983055247 @default.
- W2953450003 cites W1983236550 @default.
- W2953450003 cites W1988062260 @default.
- W2953450003 cites W1995629248 @default.
- W2953450003 cites W2001519848 @default.
- W2953450003 cites W2012953173 @default.
- W2953450003 cites W2021740841 @default.
- W2953450003 cites W2030205108 @default.
- W2953450003 cites W2031168104 @default.
- W2953450003 cites W2045809294 @default.
- W2953450003 cites W2047617378 @default.
- W2953450003 cites W2059191006 @default.
- W2953450003 cites W2061650979 @default.
- W2953450003 cites W2062934426 @default.
- W2953450003 cites W2066418831 @default.
- W2953450003 cites W2068360914 @default.
- W2953450003 cites W2075970098 @default.
- W2953450003 cites W2083308747 @default.
- W2953450003 cites W2104273768 @default.
- W2953450003 cites W2109559253 @default.
- W2953450003 cites W2119584760 @default.
- W2953450003 cites W2123271072 @default.
- W2953450003 cites W2127322768 @default.
- W2953450003 cites W2145808065 @default.
- W2953450003 cites W2152877278 @default.
- W2953450003 cites W2552904983 @default.
- W2953450003 cites W2568182039 @default.
- W2953450003 cites W2584919896 @default.
- W2953450003 cites W2611860612 @default.
- W2953450003 cites W2726737661 @default.
- W2953450003 cites W2750791471 @default.
- W2953450003 cites W2784189902 @default.
- W2953450003 cites W2784635559 @default.
- W2953450003 cites W2902995853 @default.
- W2953450003 cites W2912818999 @default.
- W2953450003 cites W2921872615 @default.
- W2953450003 cites W2941799317 @default.
- W2953450003 cites W3136918052 @default.
- W2953450003 cites W4376849538 @default.
- W2953450003 cites W93208105 @default.
- W2953450003 cites W2016522334 @default.
- W2953450003 doi "https://doi.org/10.3390/molecules24122331" @default.
- W2953450003 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6630214" @default.
- W2953450003 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31242571" @default.
- W2953450003 hasPublicationYear "2019" @default.
- W2953450003 type Work @default.
- W2953450003 sameAs 2953450003 @default.
- W2953450003 citedByCount "10" @default.
- W2953450003 countsByYear W29534500032020 @default.
- W2953450003 countsByYear W29534500032021 @default.
- W2953450003 countsByYear W29534500032022 @default.
- W2953450003 countsByYear W29534500032023 @default.
- W2953450003 crossrefType "journal-article" @default.
- W2953450003 hasAuthorship W2953450003A5010351902 @default.
- W2953450003 hasAuthorship W2953450003A5020943735 @default.
- W2953450003 hasAuthorship W2953450003A5029608207 @default.
- W2953450003 hasAuthorship W2953450003A5031324853 @default.
- W2953450003 hasAuthorship W2953450003A5035785939 @default.
- W2953450003 hasAuthorship W2953450003A5054574030 @default.
- W2953450003 hasAuthorship W2953450003A5082165691 @default.
- W2953450003 hasAuthorship W2953450003A5082294371 @default.
- W2953450003 hasBestOaLocation W29534500031 @default.
- W2953450003 hasConcept C181199279 @default.
- W2953450003 hasConcept C182996813 @default.
- W2953450003 hasConcept C184235292 @default.
- W2953450003 hasConcept C185592680 @default.
- W2953450003 hasConcept C192118531 @default.
- W2953450003 hasConcept C192527728 @default.
- W2953450003 hasConcept C2776568683 @default.
- W2953450003 hasConcept C2781462491 @default.
- W2953450003 hasConcept C55493867 @default.
- W2953450003 hasConcept C71240020 @default.
- W2953450003 hasConceptScore W2953450003C181199279 @default.
- W2953450003 hasConceptScore W2953450003C182996813 @default.
- W2953450003 hasConceptScore W2953450003C184235292 @default.
- W2953450003 hasConceptScore W2953450003C185592680 @default.
- W2953450003 hasConceptScore W2953450003C192118531 @default.
- W2953450003 hasConceptScore W2953450003C192527728 @default.