FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2111489648> ?p ?o ?g. }

• W2111489648 endingPage "1390" @default.
• W2111489648 startingPage "1375" @default.
• W2111489648 abstract "Novel azepane derivatives were prepared and evaluated for protein kinase B (PKB-alpha) and protein kinase A (PKA) inhibition. The original (-)-balanol-derived lead structure (4R)-4-(2-fluoro-6-hydroxy-3-methoxy-benzoyl)-benzoic acid (3R)-3-[(pyridine-4-carbonyl)amino]-azepan-4-yl ester (1) (IC(50) (PKB-alpha) = 5 nM) which contains an ester moiety was found to be plasma unstable and therefore unsuitable as a drug. Based upon molecular modeling studies using the crystal structure of the complex between PKA and 1, the five compounds N-[(3R,4R)-4-[4-(2-fluoro-6-hydroxy-3-methoxy-benzoyl)-benzoylamino]-azepan-3-yl]-isonicotinamide (4), (3R,4R)-N-[4-[4-(2-fluoro-6-hydroxy-3-methoxy-benzoyl)-benzyloxy]-azepan-3-yl]-isonicotinamide (5), N-[(3R,4S)-4-[4-(2-fluoro-6-hydroxy-3-methoxy-benzoyl)-phenylamino]-methyl]-azepan-3-yl)-isonicotinamide (6), N-[(3R,4R)-4-[4-(2-fluoro-6-hydroxy-3-methoxy-benzoyl)-benzylamino]-azepan-3-yl]-isonicotinamide (7), and N-[(3R,4S)-4-(4-[trans-2-[4-(2-fluoro-6-hydroxy-3-methoxy-benzoyl)-phenyl]-vinyl]-azepan-3-yl)-isonicotinamide (8) with linkers isosteric to the ester were designed, synthesized, and tested for in vitro inhibitory activity against PKA and PKB-alpha and for plasma stability in mouse plasma.(1) Compound 4 was found to be plasma stable and highly active (IC(50) (PKB-alpha) = 4 nM). Cocrystals with PKA were obtained for 4, 5, and 8 and analyzed for binding interactions and conformational changes in the ligands and protein in order to rationalize the different activities of the molecules." @default.
• W2111489648 created "2016-06-24" @default.
• W2111489648 creator A5003651055 @default.
• W2111489648 creator A5023628374 @default.
• W2111489648 creator A5055491224 @default.
• W2111489648 creator A5058422727 @default.
• W2111489648 creator A5063495689 @default.
• W2111489648 creator A5063901716 @default.
• W2111489648 creator A5065929958 @default.
• W2111489648 creator A5071243262 @default.
• W2111489648 creator A5075378760 @default.
• W2111489648 creator A5078782770 @default.
• W2111489648 creator A5079073352 @default.
• W2111489648 date "2004-02-17" @default.
• W2111489648 modified "2023-10-16" @default.
• W2111489648 title "Structure-Based Optimization of Novel Azepane Derivatives as PKB Inhibitors" @default.
• W2111489648 cites W1509578301 @default.
• W2111489648 cites W1639582946 @default.
• W2111489648 cites W1942192923 @default.
• W2111489648 cites W1956617330 @default.
• W2111489648 cites W1979012323 @default.
• W2111489648 cites W1980467950 @default.
• W2111489648 cites W1987589595 @default.
• W2111489648 cites W1992688100 @default.
• W2111489648 cites W1997611649 @default.
• W2111489648 cites W1997926000 @default.
• W2111489648 cites W2010035812 @default.
• W2111489648 cites W2016974200 @default.
• W2111489648 cites W2028231353 @default.
• W2111489648 cites W2038953220 @default.
• W2111489648 cites W2039193709 @default.
• W2111489648 cites W2039984482 @default.
• W2111489648 cites W2047759371 @default.
• W2111489648 cites W2061260658 @default.
• W2111489648 cites W2085233944 @default.
• W2111489648 cites W2087098399 @default.
• W2111489648 cites W2088472722 @default.
• W2111489648 cites W2096286606 @default.
• W2111489648 cites W2103413641 @default.
• W2111489648 cites W2118536740 @default.
• W2111489648 cites W2118882532 @default.
• W2111489648 cites W2120018526 @default.
• W2111489648 cites W2122231827 @default.
• W2111489648 cites W2141760087 @default.
• W2111489648 cites W2147114673 @default.
• W2111489648 cites W2147398227 @default.
• W2111489648 cites W2155492508 @default.
• W2111489648 cites W2286987765 @default.
• W2111489648 cites W2330787097 @default.
• W2111489648 cites W2344620397 @default.
• W2111489648 cites W2388163742 @default.
• W2111489648 cites W2615442617 @default.
• W2111489648 doi "https://doi.org/10.1021/jm0310479" @default.
• W2111489648 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/14998327" @default.
• W2111489648 hasPublicationYear "2004" @default.
• W2111489648 type Work @default.
• W2111489648 sameAs 2111489648 @default.
• W2111489648 citedByCount "91" @default.
• W2111489648 countsByYear W21114896482012 @default.
• W2111489648 countsByYear W21114896482013 @default.
• W2111489648 countsByYear W21114896482014 @default.
• W2111489648 countsByYear W21114896482015 @default.
• W2111489648 countsByYear W21114896482016 @default.
• W2111489648 countsByYear W21114896482017 @default.
• W2111489648 countsByYear W21114896482018 @default.
• W2111489648 countsByYear W21114896482019 @default.
• W2111489648 countsByYear W21114896482020 @default.
• W2111489648 countsByYear W21114896482021 @default.
• W2111489648 countsByYear W21114896482022 @default.
• W2111489648 crossrefType "journal-article" @default.
• W2111489648 hasAuthorship W2111489648A5003651055 @default.
• W2111489648 hasAuthorship W2111489648A5023628374 @default.
• W2111489648 hasAuthorship W2111489648A5055491224 @default.
• W2111489648 hasAuthorship W2111489648A5058422727 @default.
• W2111489648 hasAuthorship W2111489648A5063495689 @default.
• W2111489648 hasAuthorship W2111489648A5063901716 @default.
• W2111489648 hasAuthorship W2111489648A5065929958 @default.
• W2111489648 hasAuthorship W2111489648A5071243262 @default.
• W2111489648 hasAuthorship W2111489648A5075378760 @default.
• W2111489648 hasAuthorship W2111489648A5078782770 @default.
• W2111489648 hasAuthorship W2111489648A5079073352 @default.
• W2111489648 hasConcept C115624301 @default.
• W2111489648 hasConcept C155647269 @default.
• W2111489648 hasConcept C178790620 @default.
• W2111489648 hasConcept C181199279 @default.
• W2111489648 hasConcept C185592680 @default.
• W2111489648 hasConcept C202751555 @default.
• W2111489648 hasConcept C2776568683 @default.
• W2111489648 hasConcept C2777246417 @default.
• W2111489648 hasConcept C2777752112 @default.
• W2111489648 hasConcept C2778844314 @default.
• W2111489648 hasConcept C2779485729 @default.
• W2111489648 hasConcept C2779728014 @default.
• W2111489648 hasConcept C55493867 @default.
• W2111489648 hasConcept C71240020 @default.
• W2111489648 hasConceptScore W2111489648C115624301 @default.
• W2111489648 hasConceptScore W2111489648C155647269 @default.
• W2111489648 hasConceptScore W2111489648C178790620 @default.

• next