Matches in SemOpenAlex for { <https://semopenalex.org/work/W2791192392> ?p ?o ?g. }
- W2791192392 endingPage "2489" @default.
- W2791192392 startingPage "2472" @default.
- W2791192392 abstract "Rational design of a novel template of naphthyridinones rapidly led to PDE4 inhibitors with subnanomolar enzymatic potencies. X-ray crystallography confirmed the binding mode of this novel template. We achieved compounds with double-digit picomolar enzymatic potencies through further structure-based design by targeting both the PDE4 enzyme metal-binding pocket and occupying the solvent-filled pocket. A strategy for lung retention and long duration of action based on low aqueous solubility was followed. In vivo efficacies were measured in a rat lung neutrophilia model by suspension microspray and dry powder administration. Suspension microspray of potent compounds showed in vivo efficacy with a clear dose–response. Despite sustained lung levels, dry powder administration performed much less well and without proper dose–response, highlighting clear differences between the two formulations. This indicates a deficiency in the low aqueous solubility strategy for long duration lung efficacy." @default.
- W2791192392 created "2018-03-29" @default.
- W2791192392 creator A5000337644 @default.
- W2791192392 creator A5005759357 @default.
- W2791192392 creator A5011244775 @default.
- W2791192392 creator A5011422133 @default.
- W2791192392 creator A5020762035 @default.
- W2791192392 creator A5033902407 @default.
- W2791192392 creator A5045445557 @default.
- W2791192392 creator A5048709948 @default.
- W2791192392 creator A5050123453 @default.
- W2791192392 creator A5052223568 @default.
- W2791192392 creator A5062369842 @default.
- W2791192392 creator A5064904778 @default.
- W2791192392 creator A5075670014 @default.
- W2791192392 creator A5083380380 @default.
- W2791192392 creator A5087429346 @default.
- W2791192392 creator A5090600841 @default.
- W2791192392 date "2018-03-05" @default.
- W2791192392 modified "2023-10-10" @default.
- W2791192392 title "4-Amino-7,8-dihydro-1,6-naphthyridin-5(6<i>H</i>)-ones as Inhaled Phosphodiesterase Type 4 (PDE4) Inhibitors: Structural Biology and Structure–Activity Relationships" @default.
- W2791192392 cites W1544297197 @default.
- W2791192392 cites W1598648925 @default.
- W2791192392 cites W1604295258 @default.
- W2791192392 cites W1661704183 @default.
- W2791192392 cites W1850634138 @default.
- W2791192392 cites W1902502662 @default.
- W2791192392 cites W1906064124 @default.
- W2791192392 cites W1968620174 @default.
- W2791192392 cites W1977459493 @default.
- W2791192392 cites W1979687697 @default.
- W2791192392 cites W1997277329 @default.
- W2791192392 cites W2000025492 @default.
- W2791192392 cites W2002126352 @default.
- W2791192392 cites W2006701954 @default.
- W2791192392 cites W2007854090 @default.
- W2791192392 cites W2008442440 @default.
- W2791192392 cites W2008525757 @default.
- W2791192392 cites W2012155961 @default.
- W2791192392 cites W2018654936 @default.
- W2791192392 cites W2024599181 @default.
- W2791192392 cites W2029299795 @default.
- W2791192392 cites W2040752703 @default.
- W2791192392 cites W2052400036 @default.
- W2791192392 cites W2054621899 @default.
- W2791192392 cites W2054968345 @default.
- W2791192392 cites W2056348676 @default.
- W2791192392 cites W2061444940 @default.
- W2791192392 cites W2065538057 @default.
- W2791192392 cites W2066491159 @default.
- W2791192392 cites W2077556050 @default.
- W2791192392 cites W2079212311 @default.
- W2791192392 cites W2083802556 @default.
- W2791192392 cites W2086790377 @default.
- W2791192392 cites W2091640827 @default.
- W2791192392 cites W2095222470 @default.
- W2791192392 cites W2097771640 @default.
- W2791192392 cites W2125446149 @default.
- W2791192392 cites W2131136400 @default.
- W2791192392 cites W2133090168 @default.
- W2791192392 cites W2141030992 @default.
- W2791192392 cites W2154558722 @default.
- W2791192392 cites W2157748566 @default.
- W2791192392 cites W2159269771 @default.
- W2791192392 cites W2172258989 @default.
- W2791192392 cites W2174717129 @default.
- W2791192392 cites W2272532961 @default.
- W2791192392 cites W2316118030 @default.
- W2791192392 cites W2461375381 @default.
- W2791192392 cites W2556352052 @default.
- W2791192392 cites W4237807778 @default.
- W2791192392 cites W4253500044 @default.
- W2791192392 cites W4256102116 @default.
- W2791192392 doi "https://doi.org/10.1021/acs.jmedchem.7b01751" @default.
- W2791192392 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29502405" @default.
- W2791192392 hasPublicationYear "2018" @default.
- W2791192392 type Work @default.
- W2791192392 sameAs 2791192392 @default.
- W2791192392 citedByCount "15" @default.
- W2791192392 countsByYear W27911923922018 @default.
- W2791192392 countsByYear W27911923922019 @default.
- W2791192392 countsByYear W27911923922020 @default.
- W2791192392 countsByYear W27911923922022 @default.
- W2791192392 countsByYear W27911923922023 @default.
- W2791192392 crossrefType "journal-article" @default.
- W2791192392 hasAuthorship W2791192392A5000337644 @default.
- W2791192392 hasAuthorship W2791192392A5005759357 @default.
- W2791192392 hasAuthorship W2791192392A5011244775 @default.
- W2791192392 hasAuthorship W2791192392A5011422133 @default.
- W2791192392 hasAuthorship W2791192392A5020762035 @default.
- W2791192392 hasAuthorship W2791192392A5033902407 @default.
- W2791192392 hasAuthorship W2791192392A5045445557 @default.
- W2791192392 hasAuthorship W2791192392A5048709948 @default.
- W2791192392 hasAuthorship W2791192392A5050123453 @default.
- W2791192392 hasAuthorship W2791192392A5052223568 @default.
- W2791192392 hasAuthorship W2791192392A5062369842 @default.
- W2791192392 hasAuthorship W2791192392A5064904778 @default.
- W2791192392 hasAuthorship W2791192392A5075670014 @default.