On August 13, 2020, Crawford, James J.; Lee, Wendy; Johnson, Adam R.; Delatorre, Kelly J.; Chen, Jacob; Eigenbrot, Charles; Heidmann, Julia; Kakiuchi-Kiyota, Satoko; Katewa, Arna; Kiefer, James R.; Liu, Lichuan; Lubach, Joseph W.; Misner, Dinah; Purkey, Hans; Reif, Karin; Vogt, Jennifer; Wong, Harvey; Yu, Christine; Young, Wendy B. published an article.Synthetic Route of 87486-34-8 The title of the article was Stereochemical Differences in Fluorocyclopropyl Amides Enable Tuning of Btk Inhibition and Off-Target Activity. And the article contained the following:
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 hematol. malignancies, they are not approved for autoimmune indications. In efforts to develop addnl. series of reversible Btk inhibitors for chronic immune diseases, we sought to differentiate from our clin. 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. The experimental process involved the reaction of 3,5-Dibromo-1-methylpyrazin-2(1H)-one(cas: 87486-34-8).Synthetic Route of 87486-34-8
The Article related to fluorocyclopropyl amide btk inhibitor stereochem herg inhibition, Alicyclic Compounds: Cyclopropanes and other aspects.Synthetic Route of 87486-34-8