BENZOIC ACID DERIVATIVE AND PHARMACEUTICAL COMPOSITION

摘要

An aromatic compound of the formula (I): <IMG> wherein R1 is H, C1-8-alkyl, C1-8-haloalkyl, or -NR7R8; R2 is -C(=O)- or single bond; R3 is -OR9, three- to seven-membered saturated cycloaliphatic amino optionally interrupted by one or more N, O, or S, three- to seven-membered saturated cycloaliphatic amino containing at least one nitrogen in the ring substituted with one or more C1-8-alkyl or C1-8-haloalkyl, three- to seven-membered saturated cycloaliphatic alkyl containing at least one nitrogen in the ring optionally substituted with one or more C1-8-alkyl or C1-8-haloalkyl, or -NR10R11; R4 is H, C1-8-alkyl, C1-8-haloalkyl, -(CH2)m NR12R13, -(CH2)n R14, -(CH2)p CH(NR15R16)COOR17, -R18-COOR19, -CH(R20)OC(=O)OR21, or -CH(R22)OC(=O)R23; R10 and R11 are independently H, C1-8-alkyl, C1-8-haloalkyl, or -(CH2)q NR24R25; R14 is three-to seven-membered saturated cycloaliphatic amino optionally interrupted by one or more N, O, or S, three- to seven-membered saturated cycloaliphatic amino containing at least one nitrogen in the ring substituted with one or more C1-8-alkyl or C1-8-haloalkyl, three- to seven-membered saturated cycloaliphatic alkyl containing at least one nitrogen in the ring optionally substituted with one or more C1-8-alkyl or C1-8-haloalkyl, or three- to seven-membered unsaturated heterocyclic; R18 is three- to seven-membered saturated cycloaliphatic alkylene containing at least one nitrogen in the ring optionally substituted with one or more C1-8-alkyl or C1-8-haloalkyl; R21 and R23 are -(CH2)r R26; R26 is H, C1-8-alkyl, C1-8-haloalkyl, -NR27R28, or three- to eight-membered saturated cycloaliphatic alkyl; Z is C, CH, or N; A is CH or N; R5, R6, R7, R8, R9, R12, R13, R15, R16, R17, R19, R20, R22, R24, R25, R27, and R28 are independently H, C1-8-alkyl, or C1-8-haloalkyl; t is 0 or 1; and m, n, p, q, and r are independently 0 to 6, with the proviso that when R4 is H, C1-8-alkyl, or C1-8-haloalkyl, R3 is three- to seven-membered saturated cycloaliphatic amino containing at least one nitrogen in the ring substituted with one or more C1-8-alkyl or C1-8-haloalkyl, three- to seven-membered saturated cycloaliphatic alkyl containing at least one nitrogen in the ring optionally substituted with one or more C1-8-alkyl or C1-8-haloalkyl, or -NR10R11 wherein at least one of R10 and R11 is -(CH2)q NR24R25, or a salt thereof, and a pharmaceutical composition comprising said aromatic compound or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent are disclosed. The aromatic compound of the present invention provides a sufficiently effective alleviation of the renal dysfunction without any function to the blood pressure, and exhibits a superior behavior at a blood concentration.