1257535-15-1Relevant articles and documents
Compounds used as JAK inhibitor, and use of compounds
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, (2017/08/27)
The invention provides compounds used as a JAK inhibitor, and a use of the compounds, and concretely provides compounds (represented by formula (I)) with JAK inhibition activity or a stereoisomer, a geometric isomer, a tautomer, a racemate, a nitrogen oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, and a medicinal composition including the compounds. The invention also discloses a use of the compounds or the medicinal composition thereof in the preparation of medicines used for treating autoimmune diseases or proliferative diseases.
Strategic use of conformational bias and structure based design to identify potent JAK3 inhibitors with improved selectivity against the JAK family and the kinome
Lynch, Stephen M.,Devicente, Javier,Hermann, Johannes C.,Jaime-Figueroa, Saul,Jin, Sue,Kuglstatter, Andreas,Li, Hongju,Lovey, Allen,Menke, John,Niu, Linghao,Patel, Vaishali,Roy, Douglas,Soth, Michael,Steiner, Sandra,Tivitmahaisoon, Parcharee,Vu, Minh Diem,Yee, Calvin
, p. 2793 - 2800 (2013/07/05)
Using a structure based design approach we have identified a series of indazole substituted pyrrolopyrazines, which are potent inhibitors of JAK3. Intramolecular electronic repulsion was used as a strategy to induce a strong conformational bias within the ligand. Compounds bearing this conformation participated in a favorable hydrophobic interaction with a cysteine residue in the JAK3 binding pocket, which imparted high selectivity versus the kinome and improved selectivity within the JAK family.
