PROTEIN KINASE INHIBITORS Russian patent published in 2019 - IPC C07D487/04 A61K31/519 A61P29/00 A61P35/00 

FIELD: pharmacology.

SUBSTANCE: invention relates to a new compound of formula 1 or a pharmaceutically acceptable salt thereof having the properties of Bruton protein kinase inhibitors (Btk), Tec-Btk kinase inhibitors activated by Src kinase. The compounds can find use in preparation of a medicament for modulating the Btk kinase function and for treatment or prevention of proliferative diseases, in particular cell proliferation, inflammatory and autoimmune diseases associated with kinase activity, e.g. arthritis, immune hypersensitivity and inflammation. In formula 1, R is selected from the group consisting of 1) hydrogen, 2) C₁-C₆ alkyl, 3) C₄-C₆ carbocyclyl, 4) a 3-7 membered heterocyclyl containing one to four heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; Y is , E is selected from oxygen, Z is ,

where YEZW is selected from: , X¹ and X² are independently selected from hydrogen and halogen; m is an integer from 0 to 2, and m' is an integer from 0 to 2; W is -OR³, where R³ is selected from substituted or unsubstituted phenyl (C₁-C₆ alkyl) or substituted or unsubstituted heteroaryl(C₁-C₆ alkyl), wherein heteroaryl includes 5-6 membered ring structures which include 1 or 2 heteroatoms selected from O, N and S; phenyl(C₁-C₃ alkyl) may be further substituted by C₁-C₃ alkyl and heteroaryl(C₁-C₆ alkyl) may be further substituted by C₁-C₃ alkyl. The invention also relates to versions of the for formula 1 compounds preparation as indicated in the claims and to a pharmaceutical composition using the formula 1 compounds.

EFFECT: improved compounds properties.

17 cl, 3 tbl, 17 ex