BRK INHIBITING COMPOUND Russian patent published in 2020 - IPC C07D487/04 A61K31/519 A61K31/53 A61P35/00 

FIELD: medicine; pharmaceuticals.

SUBSTANCE: invention relates to a novel compound of general formula (I) and a pharmaceutically acceptable salt thereof. Compounds have Brk inhibitory activity and can be used as an agent for preventing and/or treating cancer, mediated by Brk activity. Said cancer is breast cancer, ovarian cancer, colon cancer, pancreatic cancer, bladder cancer, esophagus cancer, stomach cancer, non-small-cell lung cancer, prostate cancer, squamous cell carcinoma of the oral cavity, squamous cell carcinoma of the head and neck, melanoma, B-cell lymphoma and T-cell lymphoma. In compound of general formula (I)

(I) group is or ;

ring 1 is 6-member aromatic ring, optionally containing one nitrogen atom in ring or bicyclic 9–10-member ring containing 1–2 heteroatoms selected from nitrogen, oxygen or nitrogen and sulfur; R¹ denotes a halogen, an oxo group, hydroxyl group, cyano group, NR⁴R⁵, C1-4 alkyl group or C1-4 alkoxy group, where said C1-4 alkyl group or C1-4 alkoxy group can be substituted with halogen; R⁴ and R⁵ each independently represent a hydrogen atom or a C1-4 alkyl group; p is integer from 0 to 2; R³ is a C1-4 alkyl group, a group C3-6 cycloalkyl group or 3–6 membered saturated heterocycle containing an oxygen atom in a ring, where said R³ can be substituted with halogen; r is 0; s is 0; ring 2 is 5–6-membered aromatic ring, optionally containing 1–2 nitrogen or sulfur atoms in the ring or bicyclic 9-member ring, optionally containing 1 nitrogen atom as a heteroatom; R² denotes a halogen, an oxo group, a hydroxyl group, a cyano group, C(O)R⁶, SO₂R⁷, a C1-4 alkyl group or a C1-4 alkoxy group, said C1-4 alkyl group or C1-4 alkoxy group may be substituted with a substitute selected from a group consisting of halogen, hydroxyl group, cyano group, C(O)R⁸, NR⁹ R¹⁰ and SO₂R¹¹; R⁶ represents a hydroxyl group, a C1-4 alkyl group, a C1-4 alkoxy group or NR¹²R¹³; R⁷ and R¹¹ — each independently represents a C1-4 alkyl group or a C3-6 cycloalkyl group, wherein said C1-4 alkyl group may be substituted with halogen or CO₂R¹⁴; R⁸ represents a hydroxyl group, a C1-4 alkoxy group or NR¹⁵R¹⁶; R⁹, R¹⁰, R¹² and R¹³ — each independently represents a hydrogen atom or a C1-4 alkyl group which can be substituted with NR¹⁵R¹⁶; R⁹ and R¹⁰, as well as R¹² and R¹³, taken together with nitrogen atom, to which they are bonded, can form 6-member saturated cyclic amine containing a nitrogen atom and an oxygen atom as a heteroatom; R¹⁴ represents a hydrogen atom; R¹⁵ or R¹⁶ — each independently represents C1-4 alkyl, or R¹⁵ and R¹⁶, taken together with the nitrogen atom to which they are bonded, can form 6-membered saturated cyclic amine, containing a nitrogen atom or an oxygen atom as a heteroatom; q is integer from 0 to 3; provided that when p and q each represent number of 2 or more, R¹ and R² — each independently can be identical or different. Preferred are compound, which is N⁶-(1,3-dimethyl-1H-pyrazol-4-yl)-3-(1H-indol-5-yl)-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine, and a compound which is N⁶-(1,3-dimethyl-1H-pyrazol-4-yl)-3-(1H-indol-5-yl)-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine.

EFFECT: activity of the compounds with respect to Brk enables treating cancer types for which treatment of compounds mediated by other kinases, exempli gratia Syk, Jak kinases, is ineffective.

18 cl, 2 tbl