FIELD: organic chemistry, medicine, biochemistry, pharmacy.
SUBSTANCE: invention relates to derivatives of quinazoline of the general formula (I): 
and their pharmaceutically acceptable salts and in vivo hydrolyzed esters as aurorakinase inhibitors and their using, to a method for inhibition and pharmaceutical composition based on thereof, and to a method for their synthesis. In compound of the general formula (I) X represents -NR6 wherein R6 represents hydrogen atom or (C1-C6)-alkyl; R5 represents group of the formula (a): 
or (b): 
wherein * means a point for adding to group X in compound of the formula (I); R1, R2, R3 and R4 are chosen independently from hydrogen atom or -X1R9 wherein X1 represents -O-, and R9 is chosen from one of the following groups: (1) hydrogen atom or (C1-C5)-alkyl; (3) (C1-C5)-alkyl-X3R20 wherein X3 represents -O- or -NR25 wherein R25 represents hydrogen atom, (C1-C3)-alkyl or (C1-C3)-alkoxy-(C2-C3)-alkyl, and R20 represents hydrogen atom, (C1-C3)-alkyl, cyclopentyl, cyclohexyl or 5- or 6-membered saturated heterocyclic group with 1 or 2 heteroatoms that are chosen independently from nitrogen atom (N) wherein (C1-C3)-alkyl group can carry 1 or 2 substitutes that are chosen from oxo, hydroxy group, halogen atom and (C1-C4)-alkoxy group, and wherein cyclic group can carry 1 or 2 substitutes that are chosen from (C1-C4)-alkyl; (4) (C1-C5)-alkyl-X4-(C1-C5)-alkyl-X5R26 wherein X4 and X5 can be similar or different, and each means -O- or -NR31- wherein R31 represents hydrogen atom, (C1-C3)-alkyl or (C1-C3)-alkoxy-(C2-C3)-alkyl, and R26 represents hydrogen atom or (C1-C3)-alkyl; (5) R32 wherein R32 represents 5- or 6-membered saturated heterocyclic group added through carbon atom or nitrogen atom with 1 or 2 heteroatoms that are chosen independently from oxygen (O), sulfur (S) and N atoms wherein heterocyclic group can carry 1 or 2 substitutes that are chosen from hydroxy, (C1-C4)-alkyl, (C1-C4)-hydroxyalkyl, (C1-C4)-alkoxy, (C1-C4)-alkoxy-(C1-C4)-alkyl; (6) (C1-C5)-alkyl-R32 wherein R32 is given above; (18) (C1-C5)-alkyl optionally substituted with 1, 2 or 3 halogen atoms; (19) (C1-C5)-alkyl-X10-(C1-C5)-alkyl-X11R90 wherein X10 and X11 that can be similar or different each means -O- or -NR95- wherein R95 represents (C1-C5)-alkyl, (C1-C3)-alkyl substituted with 1, 2 or 3 halogen atoms, (C1-C4)-alkyl or (C1-C4)-alkoxy groups, (and wherein 2 (C1-C4)-alkoxy groups by (C1-C4)-alkyl groups alkoxy can form in common 5- or 6-membered saturated heterocyclic group that comprises 2 oxygen atoms), (C2-C5)-alkenyl, (C2-C5)-alkynyl, (C3-C6)-cycloalkyl, (C3-C6)-cycloalkyl-(C1-C3)-alkyl or (C1-C3)-alkoxy-(C2-C3)-alkyl; R90 represents hydrogen atom or (C1-C3)-alkyl; (22) (C1-C5)-alkyl-R96 wherein R96 represents 5- or 6-membered heterocyclic group that can be saturated or unsaturated (added through carbon or nitrogen atom) with 1 or 2 heteroatoms that are chosen independently from N wherein heterocyclic group can carry 1 or 2 substitutes that are chosen from (C1-C4)-hydroxyalkyl, (C1-C4)-alkyl, hydroxy and (C1-C4)-alkoxy-(C1-C4)-alkyl, and wherein R60 represents hydrogen atom; R61 represents group of the subformula (k): 
wherein p represents 0 or 1; q represents 1; R'1 and R''1 represent independently hydrogen atom or (C1-C10)-alkyl; T represents C=O; V represents -N(R63)R64 wherein R63 represents -(CH2)q'R70 or phenyl optionally substituted with 1 or 2 groups chosen independently from halogen atom, (C1-C4)-alkyl, (C1-C4)-alkoxy, trifluoromethyl, trifluoromethoxy, nitro, difluoromethyl, difluoromethoxy and cyano group; R64 represents hydrogen atom or (C1-C3)-alkyl; q' = 0; R70 represents -K-J wherein K represents a bond, and J represents phenyl optionally substituted with 1, 2 or 3 groups that are chosen from halogen atom, (C1-C3)-alkyl, cyano, (C1-C3)-alkoxy, and R62 represents hydrogen atom. Proposed compounds can be used in treatment and prophylaxis of diseases mediated by aurorakinase activity, for example, proliferative diseases, such as cancer.
EFFECT: valuable medicinal properties of compounds.
32 cl, 7 tbl, 2 sch, 147 ex
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