FIELD: chemistry; pharmaceutics.
SUBSTANCE: invention relates to a pyridone derivative having a tetrahydropyranylmethyl group represented by the following formula (I), or a pharmaceutically acceptable salt thereof, where W, X and Y each independently represent a nitrogen atom, CH, CF or C-Cl, Z denotes a nitrogen atom, CH, CF, C-Cl, CC1-C6 alkyl or CC1-C6 alkoxy group, R1 represents a group represented by following formula (II-1) or (II-2):
, where in formula (II-1) Q is a nitrogen atom, CH or CF, T is a nitrogen atom or CH, U is a nitrogen atom or CH and R6 is a halogen atom, C1-C6 alkyl group, C3-C6 cycloalkyl group, cyano group or trifluoromethoxy group, and in formula (II-2) V is a sulfur atom or an oxygen atom and R7 is C1-C6 alkyl group, R2 represents a hydrogen atom, a halogen atom, C1-C6 alkyl group, C1-C6 alkoxy group or cyano group, R3 is a hydrogen atom or C1-C6 alkyl group, R4 represents a hydrogen atom, a halogen atom or C1-C6 alkyl group and R5 represents a hydrogen atom or a group represented by the following formula (III-1), (III-2), (III-3) or (III-4):
, where in formula (III-1) R8 and R12 each independently represent a hydrogen atom or a deuterium atom, R9 represents a hydrogen atom, a halogen atom or C1-C6 alkoxy group, R10 is a hydrogen atom, C1-C6 an alkyl group optionally substituted with a heterocycloalkyl group which is a morpholinyl or methyl-substituted pyridinyl group, or C1-C6 an alkoxy group optionally substituted with a heterocycloalkyl group which is a dioxanyl, morpholinyl or pyrrolidinyl group, and R11 is a hydrogen atom, C1-C6 alkoxy group or deuterium-substituted C1-C6 alkoxy group, in formula (III-2) R13 is C1-C6 alkyl group, optionally substituted with a heterocycloalkyl group which is a dioxanyl or tetrahydropyranyl group, or a heterocycloalkyl group which is a tetrahydropyranyl group, in formula (III-3) R14 is a hydrogen atom or C1-C6 alkyl group, R15 is a hydrogen atom, C1-C6 alkyl group or C1-C6 alkoxy group and R16 represents a hydrogen atom or a halogen atom, and in formula (III-4) R17 is C1-C6 alkoxy group and R18 is C1-C6 alkoxy group. Invention also relates to crystalline forms of said compound, a pharmaceutical composition possessing Axl inhibitory activity, and medicines based thereon.
EFFECT: technical result is obtaining novel compounds and pharmaceutical compositions based thereon, which can be used in medicine in treating cancer caused by hyperfunction Axl, a disease associated with hyperfunction Axl, and/or disease accompanied by hyperfunction Axl.
53 cl, 45 tbl, 20 dwg, 123 ex
| Title | Year | Author | Number |
|---|---|---|---|
| IMIDAZOPYRIDIN-2-ONE DERIVATIVES, HAVING mTOR INHIBITING ACTIVITY | 2009 |
|
RU2478636C2 |
| HETEROCYCLIC COMPOUNDS, PHARMACEUTICAL COMPOSITION CONTAINING THEREOF AND THEIR USING | 2001 |
|
RU2289581C2 |
| DERIVATIVES OF BENZENESULPHONAMIDES AS INVERSE AGONISTS ASSOCIATED WITH RETINOIDS ROR ORPHAN GAMMA RECEPTOR (T) | 2015 |
|
RU2724331C2 |
| MKK4 PROTEIN KINASE INHIBITORS FOR STIMULATION OF LIVER REGENERATION OR REDUCTION OR PREVENTION OF HEPATOCYTE DEATH | 2019 |
|
RU2788000C2 |
| SUBSTITUTED CHROMANS | 2015 |
|
RU2718060C2 |
| PYRAZOLE DERIVATIVES APPLIED AS PROTEIN KINASE INHIBITORS | 2013 |
|
RU2623221C2 |
| PYRIDINONE AND PYRIDAZINONE DERIVATIVES | 2012 |
|
RU2632915C2 |
| PYRIDON DERIVATIVES | 2013 |
|
RU2632885C2 |
| NEW TETRAZOLE DERIVATIVES AND THEIR USE IN THE TREATMENT OF TUBERCULOSIS | 2018 |
|
RU2800930C2 |
| 2-PYRIDONE DERIVATIVES | 2010 |
|
RU2551847C2 |
