SUBSTITUTED DERIVATIVES OF QUINAZOLINE AS AURORAKINASE INHIBITORS

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