Patent RU-2386622-C2 (RU)
Inventor: MJURREJ EHNTONI
IPC: A61K31/4168
Filed: 2005-01-06
Granted: 2010-04-20
Abstract: FIELD: chemistry. 
     SUBSTANCE: invention relates to compounds of general formula (I) and to their pharmaceutically acceptable salts, optical isomers or their mixture as glucokinase activators. In general formula (I)   where R 1  is C 3-8 -cycloalkyl, C 3-8 -cycloalkenyl, a 6-member heterocyclyl with 1 nitrogen atom, condensed phenyl-C 3-8 -cycloalkyl, each of which is possibly substituted with one or two substitutes R 3 , R 4 , R 5  and R 6 ; R 2  is C 3-8 -cycloalkyl, a 5-6-member heterocyclyl with 1-2 heteroatoms selected from N, O, or S, each of which can be substituted with one or two substitutes R 30 , R 31 , R 32  and R 33 , and R 3 , R 4 , R 5 , R 6 , R 30 , R 31 , R 32  and R 33  are independently selected from a group consisting of halogen, hydroxy, oxo, -CF 3 ; or -NR 10 R 12 ; or C 1-6 -alkyl, phenyl, C 1-6 -alkoxy, C 1-6 -alkyl-C(O)-O-C 1-6 -alkyl, each of which is possibly substituted with one substitute independently selected from R 12 ; or -C(O)-R 27 , -S(O) 2 -R 27 ; or two substitutes selected from R 3 , R 4 , R 5  and R 6  or R 30 , R 31 , R 32  and R 33 , bonded to the same atom or to neighbouring atoms, together form a -O-(CH 2 ) 2 -O- radical; R 10  and R 11  independently represent hydrogen, C 1-6 -alkyl, -C(O)-C 1-6 -alkyl, -C(O)-O- C 1-6 -alkyl, -S(O) 2 - C 1-6 -alkyl; R 27  is C 1-6 -alkyl, C 1-6 -alkoxy, C 3-8 -cycloalkyl, C 3-8 -cycloalkyl-C 1-6 -alkyl, phenyl, phenyl-C 1-6 -alkyl, a 5-6-member heteroaryl with 1-2 heteroatoms selected from N or S, a 6-member heteroaryl-C 1-6 -alkyl with 1 nitrogen atom, a 6-member heterocyclyl-C 1-6 -alkyl with 1-2 heteroatoms selected from N or O, R 10 R 11 -N- C 1-6 -alkyl, each of which is possibly substituted with one substitute independently selected from R 12 ; R 12  is a halogen, CF 3 , C 1-6 -alkoxy, -NR 10 R 11 ; A is a 5-9-member heteroaryl with 1-3 heteroatoms selected from N, O or S, which is possibly substituted with one or two substitutes independently selected from R 7 , R 8  and R 9 ; R 7 , R 8  and R 9  are independently selected from halogen, cyano, -CF 3 ; or C 1-6 -alkyl, C 2-6 -alkenyl, C 1-6 -alkoxy, C 1-6 -alkylthio, -C(O)-O-C 1-6 -alkyl, formyl, - C 1-6 -alkyl-C(O)-O-C 1-6 -alkyl, -C 1-6 -alkyl-O-C(O)-C 1-6 -alkyl or hydroxy-C 1-6 -alkyl, each of which is possibly substituted with a substitute independently selected from R 16 ; or phenyl, 5-member heteroaryl-C 1-6 -alkylthio with 2-4 nitrogen atoms, phenylthio, 5-6-member heteroarylthio with 1-2 nitrogen atoms, each of which is possibly substituted on the aryl or heteroaryl part with one or two substitutes independently selected from R 17 ; or C 3-8 -cycloalkyl; or a 6-member heterocyclyl with 2 nitrogen atoms, 5-7-member heterocyclyl-C 1-6 -alkylthio with 1-2 heteroatoms selected from N or O, each of which is possibly substituted with one substitute independently selected from R 16 ; or C 1-6 -alkyl-NR 19 R 20 , -S(O) 2 -R 21  or -S(O) 2 -NR 19 R 20 ; or -C(O)NR 22 R 23 ; R 16 , R 17  and R 18  independently represent C 1-6 -alkyl, carboxy, -C(O)-O-C 1-6 -alkyl, -NR 19 R 20 , -C(O)NR 19 R 20 ; R 19  and R 20  independently represent hydrogen, C 1-6 -alkyl, phenyl, 5-member heteroaryl with 2 heteroatoms selected from N or S, 6-member heterocyclyl with 1 nitrogen atom, -C(O)-O-C 1-6 -alkyl or -S(O) 2 -C 1-6 -alkyl, each of which is possibly substituted with one substitute independently selected from R 24 ; or R 19  and R 20  together with a nitrogen atom to which they are bonded form a 5-7-member heterocyclic ring with the said nitrogen atom, where this heterocyclic ring possibly contains one additional heteroatom selected from nitrogen, oxygen and sulphur, where this heterocyclic ring is possibly substituted with one substitute independently selected from R 24 ; R 21  is selected from C 2-6 -alkenyl; or R 22  and R 23  are independently selected from hydrogen, -C 1-6 -alkyl-C(O)-O-C 1-6 -alkyl, -C 1-6 -alkyl-S(O) 2 -C 1-6 -alkyl, C 3-8 -cycloalkyl; or R 22  and R 23  together with a nitrogen atom to which they are bonded form a 6-member heterocyclic ring with the said nitrogen atom, where this heterocyclic ring is possibly substituted with one substitute independently selected from R 24 ; R 24  is oxo, C 1-6 -alkyl, carboxy- C 1-6 -alkyl, a 6-member heterocyclyl with 1 nitrogen atom, -NH-S(O) 2 R 28  or -S(O) 2 R 28 , where each cyclic group is possibly substituted with one substitute independently selected from R 29 ; R 28  is C 1-6 -alkyl, -C 1-6 -alkyl-C(O)-O- C 1-6 -alkyl or -N(CH 3 ) 2 ; R 29  is C 1-6 -alkyl. 
     EFFECT: obtaining compounds which can be used for treating and preventing diseases mediated by low glucokinase activity. 
     21 cl, 1 dwg, 608 ex, 1 tbl