FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1967081234> ?p ?o ?g. }

• W1967081234 endingPage "3792" @default.
• W1967081234 startingPage "3781" @default.
• W1967081234 abstract "The 4-hydroxy-5,6-dihydropyrone template was utilized as a flexible scaffolding from which to build potent active site inhibitors of HIV protease. Dihydropyrone 1c (5,6-dihydro-4-hydroxy-6-phenyl-3-[(2-phenylethyl)thio]-2H-pyran-2-one) was modeled in the active site of HIV protease utilizing a similar binding mode found for the previously reported 4-hydroxybenzopyran-2-ones. Our model led us to pursue the synthesis of 6,6-disubstituted dihydropyrones with the aim of filling S1 and S2 and thereby increasing the potency of the parent dihydropyrone 1c which did not fill S2. Toward this end we attached various hydrophobic and hydrophilic side chains at the 6-position of the dihydropyrone to mimic the natural and unnatural amino acids known to be effective substrates at P2 and P2‘. Parent dihydropyrone 1c (IC50 = 2100 nM) was elaborated into compounds with greater than a 100-fold increase in potency [18c, IC50 = 5 nM, 5-(3,6-dihydro-4-hydroxy-6-oxo-2-phenyl-5-[2-phenylethyl)thio]-2H-pyran-2-yl)pentanoic acid and 12c, IC50 = 51 nM, 5,6-dihydro-4-hydroxy-6-phenyl-6-(2-phenylethyl)-3-[(2-phenylethyl)thio]-2H-pyran-2-one]. Optimization of the 3-position fragment to fill S1‘ and S2‘ afforded potent HIV protease inhibitor 49 [IC50 = 10 nM, 3-[(2-tert-butyl-5-methylphenyl)sulfanyl]-5,6-dihydro-4-hydroxy-6-phenyl-6-(2-phenylethyl)-2H-pyran-2-one]. The resulting low molecular weight compounds (<475) have one or no chiral centers and are readily synthesized." @default.
• W1967081234 created "2016-06-24" @default.
• W1967081234 creator A5000652843 @default.
• W1967081234 creator A5007926534 @default.
• W1967081234 creator A5010449409 @default.
• W1967081234 creator A5013231547 @default.
• W1967081234 creator A5037802350 @default.
• W1967081234 creator A5038325057 @default.
• W1967081234 creator A5042392280 @default.
• W1967081234 creator A5043483484 @default.
• W1967081234 creator A5051234649 @default.
• W1967081234 creator A5057108969 @default.
• W1967081234 creator A5059100174 @default.
• W1967081234 creator A5059514180 @default.
• W1967081234 creator A5063555643 @default.
• W1967081234 creator A5067669966 @default.
• W1967081234 creator A5068182846 @default.
• W1967081234 creator A5070728610 @default.
• W1967081234 creator A5074223898 @default.
• W1967081234 creator A5077395512 @default.
• W1967081234 creator A5077816909 @default.
• W1967081234 creator A5079526758 @default.
• W1967081234 creator A5081334103 @default.
• W1967081234 creator A5088905337 @default.
• W1967081234 date "1997-11-01" @default.
• W1967081234 modified "2023-09-22" @default.
• W1967081234 title "4-Hydroxy-5,6-dihydropyrones. 2. Potent Non-Peptide Inhibitors of HIV Protease" @default.
• W1967081234 cites W1973792042 @default.
• W1967081234 cites W1993088940 @default.
• W1967081234 cites W2023189985 @default.
• W1967081234 cites W2040591694 @default.
• W1967081234 cites W2055129166 @default.
• W1967081234 cites W2058329882 @default.
• W1967081234 cites W2062772519 @default.
• W1967081234 cites W2078887153 @default.
• W1967081234 cites W2949621144 @default.
• W1967081234 cites W3025319364 @default.
• W1967081234 doi "https://doi.org/10.1021/jm970615f" @default.
• W1967081234 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9371244" @default.
• W1967081234 hasPublicationYear "1997" @default.
• W1967081234 type Work @default.
• W1967081234 sameAs 1967081234 @default.
• W1967081234 citedByCount "45" @default.
• W1967081234 countsByYear W19670812342012 @default.
• W1967081234 countsByYear W19670812342013 @default.
• W1967081234 countsByYear W19670812342014 @default.
• W1967081234 countsByYear W19670812342016 @default.
• W1967081234 countsByYear W19670812342018 @default.
• W1967081234 crossrefType "journal-article" @default.
• W1967081234 hasAuthorship W1967081234A5000652843 @default.
• W1967081234 hasAuthorship W1967081234A5007926534 @default.
• W1967081234 hasAuthorship W1967081234A5010449409 @default.
• W1967081234 hasAuthorship W1967081234A5013231547 @default.
• W1967081234 hasAuthorship W1967081234A5037802350 @default.
• W1967081234 hasAuthorship W1967081234A5038325057 @default.
• W1967081234 hasAuthorship W1967081234A5042392280 @default.
• W1967081234 hasAuthorship W1967081234A5043483484 @default.
• W1967081234 hasAuthorship W1967081234A5051234649 @default.
• W1967081234 hasAuthorship W1967081234A5057108969 @default.
• W1967081234 hasAuthorship W1967081234A5059100174 @default.
• W1967081234 hasAuthorship W1967081234A5059514180 @default.
• W1967081234 hasAuthorship W1967081234A5063555643 @default.
• W1967081234 hasAuthorship W1967081234A5067669966 @default.
• W1967081234 hasAuthorship W1967081234A5068182846 @default.
• W1967081234 hasAuthorship W1967081234A5070728610 @default.
• W1967081234 hasAuthorship W1967081234A5074223898 @default.
• W1967081234 hasAuthorship W1967081234A5077395512 @default.
• W1967081234 hasAuthorship W1967081234A5077816909 @default.
• W1967081234 hasAuthorship W1967081234A5079526758 @default.
• W1967081234 hasAuthorship W1967081234A5081334103 @default.
• W1967081234 hasAuthorship W1967081234A5088905337 @default.
• W1967081234 hasConcept C142462285 @default.
• W1967081234 hasConcept C181199279 @default.
• W1967081234 hasConcept C185592680 @default.
• W1967081234 hasConcept C202751555 @default.
• W1967081234 hasConcept C2776714187 @default.
• W1967081234 hasConcept C2776980637 @default.
• W1967081234 hasConcept C2777505907 @default.
• W1967081234 hasConcept C2777583353 @default.
• W1967081234 hasConcept C2777752497 @default.
• W1967081234 hasConcept C2779281246 @default.
• W1967081234 hasConcept C2779389986 @default.
• W1967081234 hasConcept C2781143361 @default.
• W1967081234 hasConcept C2781253882 @default.
• W1967081234 hasConcept C2993143319 @default.
• W1967081234 hasConcept C3013748606 @default.
• W1967081234 hasConcept C41183919 @default.
• W1967081234 hasConcept C512399662 @default.
• W1967081234 hasConcept C55493867 @default.
• W1967081234 hasConcept C57992300 @default.
• W1967081234 hasConcept C71240020 @default.
• W1967081234 hasConcept C71924100 @default.
• W1967081234 hasConceptScore W1967081234C142462285 @default.
• W1967081234 hasConceptScore W1967081234C181199279 @default.
• W1967081234 hasConceptScore W1967081234C185592680 @default.
• W1967081234 hasConceptScore W1967081234C202751555 @default.
• W1967081234 hasConceptScore W1967081234C2776714187 @default.
• W1967081234 hasConceptScore W1967081234C2776980637 @default.

• next