Patent RU-2479578-C2 (RU)
Inventor: KHISAMITI KHIROJUKI
IPC: C07D453/02
Filed: 2008-05-26
Granted: 2013-04-20
Abstract: FIELD: chemistry. 
     SUBSTANCE: invention relates to organic chemistry and specifically to novel tetrahydroisoquinolin-1-one derivatives of general formula   or pharmaceutically acceptable salts thereof, where R 1  is: lower alkylene-OH, lower alkylene-N(R 0 )(R 6 ), lower alkylene-CO 2 R 0 , C 5-6 cycloalkyl, C 6-10 cycloalkenyl, aryl, heterocyclic group, -(lower alkylen, substituted OR 0 )-aryl or lower alkylene-heterocyclic group, where the lower alkylene in R 1  can be substituted with 1-2 groups G 1 ; cycloalkyl, cycloalkenyl and heterocyclic group in R 1  can be substituted with 1-2 groups G 2 ; aryl can be substituted with 1-2 groups G 3 ; R 0 : identical or different from each other, each denotes H or a lower alkyl; R 6 : R 0 , or -S(O) 2 -lower alkyl, R 2  is: lower alkyl, lower alkylene-OR 0 , lower alkylene-aryl, lower alkylene-O-lower alkylene-aryl, -CO 2 R 0 , -C(O)N(R 0 ) 2 , -C(O)N(R 0 )-aryl, -C(O)N(R 0 )-lower alkylene-aryl, aryl or heterocyclic group, where the aryl in R 2  can be substituted with 1-3 groups G 4 ; R 3  is: H or lower alkyl, or R 2  and R 3  can be combined to form C 5 -alkylene; R 4  is: -N(R 7 )(R 8 ), -N(R 10 )-OR 7 , -N(R 0 )-N(R 0 )(R 7 ), -N(R 0 )-S(O) 2 -aryl or -N(R 0 )-S(O) 2 -R 7 , R 7  is: lower alkyl, halogen-lower alkyl, lower alkylene-CN, lower alkylene-OR 0 , lower alkylene-CO 2 R 0 , lower alkylene-C(O)N(R 0 ) 2 , lower alkylene-C(O)N(R 0 )N(R 0 ) 2 , lower alkylene-C(=NOH)NH 2 , heteroaryl, lower alkylene-X-aryl or lower alkylene-X-heterocyclic group, where the lower alkylene in R 7  can be substituted with 1-2 groups G 1 ; aryl, heteroaryl and heterocyclic group in R 7  can be substituted with 1-2 groups G 6 ; X is: a single bond, -O-, -C(O)-, -N(R 0 )-, -S(O) p - or *-C(O)N(R 0 )-, where * in X has a value ranging from a bond to a lower alkylene, m is: an integer from 0 to 1, p is: is 2, R 8  is: H, or R 7  and R 6  can be combined to form a lower alkylene-N(R 9 )-lower alkylene group, R 9  is: aryl, R 10  is: H, R 5  is: lower alkyl, halogen, nitro, -OR 0 , -N(R 0 ) 2 , or -O-lower alkylene-aryl, where the group G 1  is: -OR 0 , N(R 0 )(R 6 ) and aryl; group G 2  is: lower alkyl, lower alkylene-OR 0 , -OR 0 , -N(R 0 ) 2 , -N(R 0 )-lower alkylene-OR 0 , -N(R 0 )C(O)OR 0 , -N(R 0 )C(O)-lower alkylene-OR 0 , -N(R 0 )C(O)N(R 0 ) 2 , -N(R 0 )C(=NR 0 )-lower alkyl, -N(R 0 )S(O) 2 -lower alkyl, -N(lower alkylene-CO 2 R 0 )-S(O) 2 -lower alkyl, -N(R 0 )S(O) 2 -aryl, -N(R 0 )S(O) 2 N(R 0 ) 2 , -S(O) 2 -lower alkyl, -CO 2 R 0 , -CO 2 -lower alkylene-Si(lower alkyl) 3 , -C(O)N(R 0 ) 2 , -C(O)N(R 0 )-lower alkylene-OR 0 , -C(O)N(R 0 )-lower alkylene-N(R 0 ) 2 , -C(O)N(R 0 )-lower alkylene-CO 2 R 0 , -C(O)N(R 0 )-O-lower alkylene-heterocyclic group, -C(O)R 0 , -C(O)-lower alkylene-OR 0 , C(O)-heterocyclic group and oxo; under the condition that "aryl" in group G 2  can be substituted with one lower alkyl; group G 3  is: -OR 0 ; group G 4  is: halogen, CN, nitro, lower alkyl, -OR 0 , -N(R 0 ) 2)  -CO 2 R 0 ; group G 5  is: halogen, -OR 0 , -N(R 0 ) 2  and aryl; group G 6  is: halogen, lower alkyl which can be substituted with -OR 0 , halogen-lower alkyl which is substituted with -OR 0 , -OR 0 , -CN, -N(R 0 ) 2 , -CO 2 R 0 , -C(O)N(R 0 ) 2 , lower alkylene-OC(O)R 0 , lower alkylene-OC(O)-aryl, lower alkylene-CO 2 R 0 , halogen-lower alkylene-CO 2 R 0 , lower alkylene-C(O)]N(R 0 ) 2 , halogen-lower alkylene-C(O)N(R 0 )2, -O-lower alkylene-CO 2 R 0 , -O-lower alkylene-CO 2 -lower alkylene-aryl, -C(O)N(R 0 )S(O) 2 -lower alkyl, lower alkylene-C(O)N(R 0 )S(O) 2 -lower alkyl, -S(O) 2 -lower alkyl, -S(O) 2 N(R 0 ) 2 , heterocyclic group, -C(-NH)=NO-C(O)O-C 1-10 -alkyl, -C(=NOH)NH 2 , C(O)N=C(N(R 0 ) 2 ) 2 , -N(R 0 )C(O)R 0 , -N(R 0 )C(O)-lower alkylene-OR 0 , -N(R 0 )C(O)OR 0 , -C(aryl) 3  and oxo; under the condition that the "heterocyclic group" in group G 6  is substituted with 1 group selected from a group consisting of -OR 0 , oxo and thioxo (=S); where the "cycloalkenyl" relates to C 5-10  cycloalkenyl, including a cyclic group which is condensed with a benzene ring at the site of the double bond; the "aryl" relates to an aromatic monocyclic C 6 -hydrocarbon group; the "heterocyclic group" denotes a cyclic group consisting of i) a monocyclic 5-6-member heterocycle having 1-4 heteroatoms selected from O, S and N, or ii) a bicyclic 8-9-member heterocycle having 1-3 heteroatoms selected from O, S and N, obtained via condensation of the monocyclic heterocycle and one ring selected from a group consisting of a monocyclic heterocycle, a benzene ring, wherein the N ring atom can be oxidised to form an oxide; the "heteroaryl" denotes pyridyl or benzimidazolyl; provided that existing compounds given in claim 1 of the invention are excluded. The invention also relates to a pharmaceutical composition based on the compound of formula (I), use of the compound of formula (I) and a method of treatment using the compound of formula (I). 
     EFFECT: obtaining novel tetrahydroisoquinolin-1-one derivatives which are useful as a BB2 receptor antagonist. 
     11 cl, 302 tbl, 59 ex