881415-30-1Relevant articles and documents
CHEMICAL COMPOUNDS
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, (2021/01/23)
The present disclosure describes novel compounds, or their pharmaceutically acceptable salts, pharmaceutical compositions containing them, and their medical uses. Compounds of the disclosure have activity as dual modulators of Janus kinase (JAK), alone, or in combination with one or more of an additional mechanism, including a tyrosine kinase, such as TrkA or Syk, and PDE4, and are useful in the in the treatment or control of inflammation, auto-immune diseases, cancer, and other disorders and indications where modulation of JAK would be desirable. Also described herein are methods of treating inflammation, auto-immune diseases, cancer, and other conditions susceptible to inhibition of JAK and PDE4 by administering a compound herein described.
Discovery of Phenylglycine Lactams as Potent Neutral Factor VIIa Inhibitors
Wurtz, Nicholas R.,Parkhurst, Brandon L.,Jiang, Wen,DeLucca, Indawati,Zhang, Xiaojun,Ladziata, Vladimir,Cheney, Daniel L.,Bozarth, Jeffrey R.,Rendina, Alan R.,Wei, Anzhi,Luettgen, Joseph M.,Wu, Yiming,Wong, Pancras C.,Seiffert, Dietmar A.,Wexler, Ruth R.,Priestley, E. Scott
supporting information, p. 1077 - 1081 (2016/12/18)
Inhibitors of Factor VIIa (FVIIa), a serine protease in the clotting cascade, have shown strong antithrombotic efficacy in preclinical thrombosis models with minimal bleeding liabilities. Discovery of potent, orally active FVIIa inhibitors has been largely unsuccessful because known chemotypes have required a highly basic group in the S1 binding pocket for high affinity. A recently reported fragment screening effort resulted in the discovery of a neutral heterocycle, 7-chloro-3,4-dihydroisoquinolin-1(2H)-one, that binds in the S1 pocket of FVIIa and can be incorporated into a phenylglycine FVIIa inhibitor. Optimization of this P1 binding group led to the first series of neutral, permeable FVIIa inhibitors with low nanomolar potency.
