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 R1 is: lower alkylene-OH, lower alkylene-N(R0)(R6), lower alkylene-CO2R0, C5-6cycloalkyl, C6-10cycloalkenyl, aryl, heterocyclic group, -(lower alkylen, substituted OR0)-aryl or lower alkylene-heterocyclic group, where the lower alkylene in R1 can be substituted with 1-2 groups G1; cycloalkyl, cycloalkenyl and heterocyclic group in R1 can be substituted with 1-2 groups G2; aryl can be substituted with 1-2 groups G3; R0: identical or different from each other, each denotes H or a lower alkyl; R6: R0, or -S(O)2-lower alkyl, R2 is: lower alkyl, lower alkylene-OR0, lower alkylene-aryl, lower alkylene-O-lower alkylene-aryl, -CO2R0, -C(O)N(R0)2, -C(O)N(R0)-aryl, -C(O)N(R0)-lower alkylene-aryl, aryl or heterocyclic group, where the aryl in R2 can be substituted with 1-3 groups G4; R3 is: H or lower alkyl, or R2 and R3 can be combined to form C5-alkylene; R4 is: -N(R7)(R8), -N(R10)-OR7, -N(R0)-N(R0)(R7), -N(R0)-S(O)2-aryl or -N(R0)-S(O)2-R7, R7 is: lower alkyl, halogen-lower alkyl, lower alkylene-CN, lower alkylene-OR0, lower alkylene-CO2R0, lower alkylene-C(O)N(R0)2, lower alkylene-C(O)N(R0)N(R0)2, lower alkylene-C(=NOH)NH2, heteroaryl, lower alkylene-X-aryl or lower alkylene-X-heterocyclic group, where the lower alkylene in R7 can be substituted with 1-2 groups G1; aryl, heteroaryl and heterocyclic group in R7 can be substituted with 1-2 groups G6; X is: a single bond, -O-, -C(O)-, -N(R0)-, -S(O)p- or *-C(O)N(R0)-, 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, R8 is: H, or R7 and R6 can be combined to form a lower alkylene-N(R9)-lower alkylene group, R9 is: aryl, R10 is: H, R5 is: lower alkyl, halogen, nitro, -OR0, -N(R0)2, or -O-lower alkylene-aryl, where the group G1 is: -OR0, N(R0)(R6) and aryl; group G2 is: lower alkyl, lower alkylene-OR0, -OR0, -N(R0)2, -N(R0)-lower alkylene-OR0, -N(R0)C(O)OR0, -N(R0)C(O)-lower alkylene-OR0, -N(R0)C(O)N(R0)2, -N(R0)C(=NR0)-lower alkyl, -N(R0)S(O)2-lower alkyl, -N(lower alkylene-CO2R0)-S(O)2-lower alkyl, -N(R0)S(O)2-aryl, -N(R0)S(O)2N(R0)2, -S(O)2-lower alkyl, -CO2R0, -CO2-lower alkylene-Si(lower alkyl)3, -C(O)N(R0)2, -C(O)N(R0)-lower alkylene-OR0, -C(O)N(R0)-lower alkylene-N(R0)2, -C(O)N(R0)-lower alkylene-CO2R0, -C(O)N(R0)-O-lower alkylene-heterocyclic group, -C(O)R0, -C(O)-lower alkylene-OR0, C(O)-heterocyclic group and oxo; under the condition that "aryl" in group G2 can be substituted with one lower alkyl; group G3 is: -OR0; group G4 is: halogen, CN, nitro, lower alkyl, -OR0, -N(R0)2) -CO2R0; group G5 is: halogen, -OR0, -N(R0)2 and aryl; group G6 is: halogen, lower alkyl which can be substituted with -OR0, halogen-lower alkyl which is substituted with -OR0, -OR0, -CN, -N(R0)2, -CO2R0, -C(O)N(R0)2, lower alkylene-OC(O)R0, lower alkylene-OC(O)-aryl, lower alkylene-CO2R0, halogen-lower alkylene-CO2R0, lower alkylene-C(O)]N(R0)2, halogen-lower alkylene-C(O)N(R0)2, -O-lower alkylene-CO2R0, -O-lower alkylene-CO2-lower alkylene-aryl, -C(O)N(R0)S(O)2-lower alkyl, lower alkylene-C(O)N(R0)S(O)2-lower alkyl, -S(O)2-lower alkyl, -S(O)2N(R0)2, heterocyclic group, -C(-NH)=NO-C(O)O-C1-10-alkyl, -C(=NOH)NH2, C(O)N=C(N(R0)2)2, -N(R0)C(O)R0, -N(R0)C(O)-lower alkylene-OR0, -N(R0)C(O)OR0, -C(aryl)3 and oxo; under the condition that the "heterocyclic group" in group G6 is substituted with 1 group selected from a group consisting of -OR0, oxo and thioxo (=S); where the "cycloalkenyl" relates to C5-10 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 C6-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
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