Patent RU-2517194-C2 (RU)
Inventor: LE KHJUROU IVAN
IPC: A61K31/437
Filed: 2009-05-13
Granted: 2014-05-27
Abstract: FIELD: chemistry. 
     SUBSTANCE: invention concerns novel compounds of formula I:   and stereoisomers, tautomers and pharmaceutically acceptable salt thereof, where: A is selected from a single bond or CR a R b ; R 1  is selected from hydrogen, halogen, CN, C 1 -C 6 alkyl, C 1 -C 6 alkenyl, -O(C 1 -C 6 alkyl), -S(C 1 -C 6 alkyl), C 3 -C 6 cycloalkyl, 4-6-member heterocycle containing one, two or three heteroatoms selected from a group consisting of oxygen, nitrogen and sulphur, phenyl and a 5- or 6-member heteroaryl containing one, two or three heteroatoms, selected from a group consisting of oxygen, nitrogen and sulphur, where the alkyls, alkenyl, cycloalkyl, heterocycle, phenyl or heteroaryl are optionally substituted with one or more groups selected from halogen, CN, CF 3 , C 1 -C 3 alkyl, -O(C 1 -C 3 alkyl) and NR c R d ; R 2  is selected from C 1 -C 6 alkyl, -O(C 1 -C 6 alkyl), -NH(C 1 -C 6 alkyl), saturated or partially unsaturated C 3 -C 6 cycloalkyl, phenyl, saturated or partially unsaturated 4-6-member heterocycle containing one, two or three heteroatoms selected from a group consisting of oxygen, nitrogen an sulphur, 5- or 6-member heteroaryl containing one, two or three heteroatoms selected from a group consisting of oxygen, nitrogen and sulphur, 8-10-member bicyclic aryl, 8-10-member bicyclic heterocycle containing one, two or three heteroatoms selected from a group consisting of oxygen, nitrogen and sulphur, and an 8-10-mbmer bicyclic heteroaryl containing one, two or three heteroatoms selected from a group consisting of oxygen, nitrogen and sulphur, where the alkyls, cycloalkyl, phenyl, heteocycles, heteroaryls and aryl are optionally substituted with one or more groups selected from OH, CN, halogen, oxo (except substitutes in the pheny, aryl or heteroaryl), CF 3 , cyclopropyl, cyclopropylmethyl, -SO 2 R i , C 1 -C 6 alkyl, -O(C 1 -C 6 alkyl), -S(C 1 -C 6 alkyl), NR e R f  and phenyl, where the phenyl is optionally substituted with one or more groups selected from OH, CN, halogen, CF 3 , C 1 -C 3 alkyl, -O(C 1 -C 3 alkyl) and NR g R h ; R 3  and R 4  are independently selected from hydrogen or C 1 -C 4 alkyl, optionally substituted with OH, F, -O(C 1 -C 3 alkyl) or C 3 -C 6 cycloalkyl, or R 3  and R 4 , together with atoms with which they are bonded, form a 5- or 6-member ring; R 5  is selected from hydrogen and CH 3 , or A is CR a R b , R a  and R b  denote hydrogen, and R 3  and R 5 , together with atoms with which they are bonded, form a 5- or 6-member ring; R 6  is selected from hydrogen, F, OH, -OCH 3 , C 1 -C 3 alkyl and cyclopropyl, or A is a single bond, R 6a  is hydrogen, and R 3  and R 6 , together with atoms with which they are bonded, form a 5- or 6-member ring; R 6a  is selected from hydrogen, F, OH and CH 3 ; R 7  is hydrogen, or A is CR a R b  and R 3  and R 7 , together with atoms with which they are bonded, form a 5- or 6-member ring; R a  is hydrogen, or R 4  and R b  are absent, and R 3  and R a , together with atoms with which they are bonded, form a 5- or 6-member aromatic ring; R b  is hydrogen or is absent; R c  and R d  are independently selected from hydrogen and C 1 -C 3 alkyl, or R c  and R d , together with atoms with which they are bonded, form a 5- or 6-member ring; R e  and R f  are independently selected from a hydrogen and C 1 -C 3 alkyl; R g  R h  are independently selected from hydrogen and C 1 -C 3 alkyl; R i  is C 1 -C 3 alkyl; and p equals 0, 1, 2 or 3. The invention also relates to a pharmaceutical composition based on compounds of formula I, having inhibiting activity on CHK1 and/or CHK2, a method of preventing or treating a disease or disorder modulated by CHK1, a method of treating a hyperproliferative disease. The invention also relates to a method of producing a compound of formula I. 
     EFFECT: novel biologically active compounds, which can be suitable for inhibiting CHK1 and/or CHK2, are obtained and described. 
     96 cl, 184 ex, 1 tbl