NOVEL COUMARIN DERIVATIVES WITH ANTI-TUMOUR ACTIVITY Russian patent published in 2011 - IPC C07D311/18 C07D401/06 C07D405/12 C07D405/14 C07D417/12 C07D491/52 A61K31/352 A61K31/427 A61K31/443 A61K31/506 A61P35/00 

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (11) given below and pharmaceutically acceptable salts thereof: chemical formula 1

in which: each of G¹, G², G³ and G⁸ independently denotes -N=, -CR¹= or -C(-G⁹-X)=; one of G¹, G², G³ and G⁸ is-C(-G⁹-X)=; X is C_1-6 alkyl (where C_1-6 can be optionally substituted with a group selected from a halogen atom, hydroxy, cyano and -NR⁵⁶R⁵⁷), aryl, heterocycle (where the heterocycle denotes a 5-9-member saturated or unsaturated cyclic group containing one or more heteroatoms selected from nitrogen, oxygen and sulphur atoms, and can be a monocycle or condensed ring, and can be optionally substituted with a halogen atom, C_1-6 alkyl; C_1-6 alkoxy, R³³R³⁴NCS-, R³R⁴NCO-); G⁹ denotes a single bond, an oxygen atom, a sulphur atom, ring G⁶ denotes a divalent aryl group or divalent pyridyl group (where the divalent pyridyl group can be optionally substituted with a halogen atom); A is a group of formula (2) given below, or a group of formula (3) given below. Chemical formula 2

, chemical formula 3 , G⁴ is an oxygen atom or sulphur atom; G⁵ is an oxygen atom or sulphur atom; G⁷ is an oxygen atom, -CR⁴²R⁴³-, -CONR⁴⁴-, -NR⁴⁴CO, -NR⁴⁵-, CR⁴²R⁴³NR⁴⁵-, -S-, -NR⁴⁴S(=O)₂-; R¹ is a hydrogen atom, a halogen atom, cyano, C_1-6 alkyl (where C_1-6 alkyl can be optionally substituted with a halogen atom), carbamoyl or C_2-7 alkynyl (where C_2-7 alkynyl can be optionally substituted with C_1-4 acyl); when G² or G³ denotes -CR¹=, then G⁸ is -C(-G⁹-X)=, and X is R³R⁴NCO-, R³³R³⁴NCS-; when G⁸ is -CR¹=, then G³ denotes -C(-G⁹-X)=, and X is R³R⁴NCO, or R³³R³⁴NCS-; when G¹ or G⁸ denotes -CR⁴ then G² is -C(-G⁹-X)=, and X denotes R³R⁴NCO-, or R³³R³⁴NCS-; or when G² is -CR¹=, then G¹ denotes -C(-G⁹-X)=, and X denotes R³R⁴NCO-, or R³³R³⁴NCS-; R¹ can form a single bond or -CH₂- with R⁴ or R³⁴; R² denotes hydroxy or C_1-6 alkyl (where C_1-6 alkyl can be optionally substituted with a group selected from a halogen atom, hydroxy, C_1-6 alkoxy, formyl and -CO₂R⁵⁰); R³, R⁴, R⁹ and R¹⁰ each independently denotes a hydrogen atom, C_3-8 cycloalkyl or C_1-6 alkyl (where C_1-6 alkyl can be optionally substituted with a group selected from cyano, a halogen atom, hydroxy, C_1-6 alkoxy, -NR¹³R¹⁴, and CONR²⁸R²⁹); R⁶ and R⁷ each independently denotes a hydrogen atom, C_1-6 alkoxy, C_3-8 cycloalkyl or C_1-6 alkyl (where C_1-6 alkyl can be optionally substituted with a group selected from cyano, halogen atom, hydroxy, C_1-6 alkoxy, -NR¹³R¹⁴, and CONR²⁸R²⁹); R³³ and R³⁴ each independently denotes a hydrogen atom, C_1-6 alkyl, the combination of R³ and R⁴ together with a nitrogen atom to which they are bonded can form a 5-6-member heterocyclic group containing at least one nitrogen atom (where the 5-6-member heterocyclic group which contains at least one nitrogen atom is a saturated or unsaturated heterocyclic group containing 5-6 atoms in the ring and which, in addition to one or more nitrogen atoms, can contain one or more heteroatoms selected from oxygen and sulphur atoms (where the 5-6-member heterocyclic group can be optionally condensed with a benzene ring); and which can be optionally substituted with a halogen atom or C_1-6 alkyl; the combination of R⁶ and R⁷ together with the nitrogen atom to which they are bonded can form a 5-6-member heterocyclic group containing at least one nitrogen atom (where the 5-6-member heterocyclic group which contains at least one nitrogen atom is a saturated or unsaturated heterocyclic group containing 5-6 atoms in the ring and which, in addition to one or more nitrogen atoms, can contain one or more heteroatoms selected from oxygen and sulphur atoms (where the 5-6-member heterocyclic group can be optionally condensed with a benzene ring); and which can be optionally substituted with a halogen atom, C_1-6 alkyl or an oxo group; R⁴⁵ is a hydrogen atom, R¹³ and R¹⁴ each independently denotes a hydrogen atom, C_1-6 alkyl or COR³²; R⁵⁶ and R⁵⁷ each independently denotes a hydrogen atom or C_1-6 alkyl, and R⁵, R⁸, R²⁸, R²⁹, R³², R⁴², R⁴³, R⁴⁴, and R⁵⁰ each independently denotes a hydrogen atom or C_1-6 alkyl. The invention also relates to a pharmaceutical composition, as well as to a medicinal agent for treating cell proliferative disorder.

EFFECT: obtaining novel biologically active compounds having inhibitory effect on cell proliferation.

15 cl, 2 tbl