FGFR4 INHIBITORS

FIELD: medicine; pharmaceuticals.SUBSTANCE: invention relates to a novel compound of formula I or a pharmaceutically acceptable salt thereof. Compound has FGF19 inhibitor activity and can be used to treat a disorder which has at least one altered FGF19 status and a changed FGFR4 status. In particular, the compound can be used for treating hepatocyte carcinoma, which has at least one altered status of FGF19 with high expression of FGFR4. In formula I,Ris selected from a group consisting of Calkyl, CalkoxyCalkyl, NRRCalkyl, RheterocyclylCalkyl, where the heterocyclyl group is selected from 5-6 membered saturated heterocyclyl and 5-6 member heteroaryl containing 1-2 heteroatoms selected from i) one nitrogen atom, ii) two nitrogen atoms and iii) one nitrogen atom and one oxygen atom, RarylCalkyl, where aryl is phenyl, and where Rand R, each independently selected from a group consisting of hydrogen and Calkyl; E is selected from a group consisting of -NRC(O)CR=CHRand -NRC(O)C≡CR, where Ris selected from a group consisting of hydrogen and methyl, Ris selected from a group consisting of hydrogen, methyl and fluorine; and Ris selected from a group consisting of hydrogen, methyl and chlorine; Ris selected from a group consisting of hydrogen, halogen, Calkyl, Calkoxy, hydroxyCalkyl, hydroxyCalkoxy, CalkoxyCalkoxy, CalkoxyCalkyl, RRheterocyclyl, -C(O)heterocyclylRR, RRheterocyclylCalkyl, NRR, NRRCalkyl, -C(O)NRRand NRRCalkoxy, where each heterocyclyl is selected from 6-member saturated heterocycle containing 1-2 heteroatoms selected from nitrogen or nitrogen and oxygen, and Rand R, each independently selected from a group consisting of hydrogen, Calkyl, hydroxyCalkyl, aminoCalkyl, -C(O)Calkyl and Calkylsulphonyl; and Ris phenyl, where said phenyl is substituted with 2, 3 or 4 substitutes independently selected from halogen or Calkoxy.EFFECT: compound can be used for treating cholangiocarcinoma or rhabdomyosarcoma of expressing or overexpressing FGFR4.34 cl, 2 dwg, 6 tbl, 185 ex Изобретение относится к новому соединению формулы I или его фармацевтически приемлемой соли. Соединение обладает активностью в отношении ингибитора FGF19 и может быть использовано для лечения расстройства, которое имеет по меньшей мере один измененный статус FGF19 и измененный статус FGFR4. В частности соединение может быть использовано для лечения гепато-клеточной карциномы, которая имеет по меньшей мере один измененный статус FGF19 с повышенной экспрессией FGFR4. Соединение может быть испол