Matches in SemOpenAlex for { <https://semopenalex.org/work/W3043282853> ?p ?o ?g. }
- W3043282853 endingPage "1597" @default.
- W3043282853 startingPage "1588" @default.
- W3043282853 abstract "Bruton’s tyrosine kinase (Btk) is thought to play a pathogenic role in chronic immune diseases such as rheumatoid arthritis and lupus. While covalent, irreversible Btk inhibitors are approved for treatment of hematologic malignancies, they are not approved for autoimmune indications. In efforts to develop additional series of reversible Btk inhibitors for chronic immune diseases, we sought to differentiate from our clinical stage inhibitor fenebrutinib using cyclopropyl amide isosteres of the 2-aminopyridyl group to occupy the flat, lipophilic H2 pocket. While drug-like properties were retained—and in some cases improved—a safety liability in the form of hERG inhibition was observed. When a fluorocyclopropyl amide was incorporated, Btk and off-target activity was found to be stereodependent and a lead compound was identified in the form of the (R,R)- stereoisomer." @default.
- W3043282853 created "2020-07-23" @default.
- W3043282853 creator A5003518387 @default.
- W3043282853 creator A5006218365 @default.
- W3043282853 creator A5009186086 @default.
- W3043282853 creator A5013189744 @default.
- W3043282853 creator A5018363968 @default.
- W3043282853 creator A5025969569 @default.
- W3043282853 creator A5036471734 @default.
- W3043282853 creator A5038861396 @default.
- W3043282853 creator A5047103839 @default.
- W3043282853 creator A5049254683 @default.
- W3043282853 creator A5059271995 @default.
- W3043282853 creator A5059406597 @default.
- W3043282853 creator A5059479187 @default.
- W3043282853 creator A5066900396 @default.
- W3043282853 creator A5071889722 @default.
- W3043282853 creator A5079978881 @default.
- W3043282853 creator A5085310293 @default.
- W3043282853 creator A5087326334 @default.
- W3043282853 creator A5087537750 @default.
- W3043282853 date "2020-07-13" @default.
- W3043282853 modified "2023-10-10" @default.
- W3043282853 title "Stereochemical Differences in Fluorocyclopropyl Amides Enable Tuning of Btk Inhibition and Off-Target Activity" @default.
- W3043282853 cites W1813485308 @default.
- W3043282853 cites W1975947882 @default.
- W3043282853 cites W1977363854 @default.
- W3043282853 cites W1982411778 @default.
- W3043282853 cites W1983401069 @default.
- W3043282853 cites W1986581600 @default.
- W3043282853 cites W1997513635 @default.
- W3043282853 cites W1998822811 @default.
- W3043282853 cites W2002285059 @default.
- W3043282853 cites W2009289049 @default.
- W3043282853 cites W2011178741 @default.
- W3043282853 cites W2019216438 @default.
- W3043282853 cites W2033867789 @default.
- W3043282853 cites W2038094422 @default.
- W3043282853 cites W2050025801 @default.
- W3043282853 cites W2052690081 @default.
- W3043282853 cites W2061501938 @default.
- W3043282853 cites W2067313345 @default.
- W3043282853 cites W2078275018 @default.
- W3043282853 cites W2093522627 @default.
- W3043282853 cites W2100085975 @default.
- W3043282853 cites W2115629214 @default.
- W3043282853 cites W2141271295 @default.
- W3043282853 cites W2145138842 @default.
- W3043282853 cites W2157486761 @default.
- W3043282853 cites W2158001769 @default.
- W3043282853 cites W2163431182 @default.
- W3043282853 cites W2163690533 @default.
- W3043282853 cites W2172609141 @default.
- W3043282853 cites W2237850791 @default.
- W3043282853 cites W2250687747 @default.
- W3043282853 cites W2296618733 @default.
- W3043282853 cites W2405533405 @default.
- W3043282853 cites W2564350518 @default.
- W3043282853 cites W2604620912 @default.
- W3043282853 cites W2611512307 @default.
- W3043282853 cites W2788356134 @default.
- W3043282853 cites W2898934414 @default.
- W3043282853 cites W2962182289 @default.
- W3043282853 cites W2972482801 @default.
- W3043282853 cites W2995673532 @default.
- W3043282853 cites W3033713239 @default.
- W3043282853 cites W4253960665 @default.
- W3043282853 doi "https://doi.org/10.1021/acsmedchemlett.0c00249" @default.
- W3043282853 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7430973" @default.
- W3043282853 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32832028" @default.
- W3043282853 hasPublicationYear "2020" @default.
- W3043282853 type Work @default.
- W3043282853 sameAs 3043282853 @default.
- W3043282853 citedByCount "12" @default.
- W3043282853 countsByYear W30432828532021 @default.
- W3043282853 countsByYear W30432828532022 @default.
- W3043282853 countsByYear W30432828532023 @default.
- W3043282853 crossrefType "journal-article" @default.
- W3043282853 hasAuthorship W3043282853A5003518387 @default.
- W3043282853 hasAuthorship W3043282853A5006218365 @default.
- W3043282853 hasAuthorship W3043282853A5009186086 @default.
- W3043282853 hasAuthorship W3043282853A5013189744 @default.
- W3043282853 hasAuthorship W3043282853A5018363968 @default.
- W3043282853 hasAuthorship W3043282853A5025969569 @default.
- W3043282853 hasAuthorship W3043282853A5036471734 @default.
- W3043282853 hasAuthorship W3043282853A5038861396 @default.
- W3043282853 hasAuthorship W3043282853A5047103839 @default.
- W3043282853 hasAuthorship W3043282853A5049254683 @default.
- W3043282853 hasAuthorship W3043282853A5059271995 @default.
- W3043282853 hasAuthorship W3043282853A5059406597 @default.
- W3043282853 hasAuthorship W3043282853A5059479187 @default.
- W3043282853 hasAuthorship W3043282853A5066900396 @default.
- W3043282853 hasAuthorship W3043282853A5071889722 @default.
- W3043282853 hasAuthorship W3043282853A5079978881 @default.
- W3043282853 hasAuthorship W3043282853A5085310293 @default.
- W3043282853 hasAuthorship W3043282853A5087326334 @default.
- W3043282853 hasAuthorship W3043282853A5087537750 @default.
- W3043282853 hasBestOaLocation W30432828532 @default.