| 摘要 |
The present invention relates to a morphinan derivative represented by the following general formula (I), wherein R1 represents hydrogen, C1-6 alkyl, C6-10 aryl, etc., R2 and R3, which are the same or different, represent hydrogen, hydroxy, etc., R4 and R5 represent hydrogen, C1-6 alkyl, etc., R6 represents hydrogen, hydroxy, C1-6 alkyl, etc., X represents O or CH2, Y represents C═O, C(═O)O, etc., and m and n, which are the same or different, represent an integer of 0 to 2 (m and n are not 0 at the same time), a tautomer or stereoisomer of the compound, or a pharmaceutically acceptable salt thereof, or a solvate thereof, as well as an analgesic, antianxiety drug, etc. containing the same as an active ingredient.; |
| 主权项 |
1. A morphinan compound represented by the following formula (I), a tautomer or stereoisomer of the compound, or a pharmaceutically acceptable salt or solvate thereof:wherein,
R1 represents hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, heteroaryl containing 1 to 4 heteroatoms selected from N, O, and S as a ring-constituting atom, aralkyl in which the aryl moiety has 6 to 10 carbon atoms and the alkylene moiety has 1 to 5 carbon atoms, heteroarylalkyl in which the heteroaryl contains 1 to 4 heteroatoms selected from N, O, and S as a ring-constituting atom and the alkylene moiety has 1 to 5 carbon atoms, cycloalkylalkyl in which the cycloalkyl moiety has 3 to 6 carbon atoms and the alkylene moiety has 1 to 5 carbon atoms, C2-6 alkenyl, arylalkenyl in which the aryl moiety has 6 to 10 carbon atoms and the alkenyl moiety has 2 to 6 carbon atoms, heteroarylalkenyl in which the heteroaryl contains 1 to 4 heteroatoms selected from N, O, and S as a ring-constituting atom and the alkenyl moiety has 2 to 6 carbon atoms, cycloalkylalkenyl in which the cycloalkyl moiety has 3 to 6 carbon atoms and the alkenyl moiety has 2 to 6 carbon atoms, C4-6 cycloalkenyl, cycloalkenylalkyl in which the cycloalkenyl moiety has 4 to 6 carbon atoms and the alkylene moiety has 1 to 5 carbon atoms, or cycloalkenylalkenyl in which the cycloalkenyl moiety has 4 to 6 carbon atoms and the alkenyl moiety has 2 to 6 carbon atoms, R2 and R3, which are the same or different, represent hydrogen, hydroxy, cyano, carbamoyl, C1-6 alkoxy, C6-10 aryloxy, or C1-6 alkanoyloxy, R4 and R5, which are the same or different, represent hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, cycloalkylalkyl in which the cycloalkyl moiety has 3 to 6 carbon atoms and the alkylene moiety has 1 to 5 carbon atoms, aralkyl in which the aryl moiety has 6 to 10 carbon atoms and the alkylene moiety has 1 to 5 carbon atoms, or heteroarylalkyl in which the heteroaryl contains 1 to 4 heteroatoms selected from N, O, and S as a ring-constituting atom and the alkylene moiety has 1 to 5 carbon atoms, or R5 and R4 may combine together to form a 4- to 7-membered ring, which may contain a heteroatom selected from N, O, and S as a ring-constituting atom other than the N atom to which R5 binds, provided the ring is not a heteroaryl, together with the nitrogen atom to which R5 binds, R6 represents hydrogen, hydroxy, C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, cycloalkylalkyl in which the cycloalkyl moiety has 3 to 6 carbon atoms and the alkylene moiety has 1 to 5 carbon atoms, aralkyl in which the aryl moiety has 6 to 10 carbon atoms and the alkylene moiety has 1 to 5 carbon atoms, or heteroarylalkyl in which the heteroaryl contains 1 to 4 heteroatoms selected from N, O, and S as a ring-constituting atom and the alkylene moiety has 1 to 5 carbon atoms, or R6 and R5 may combine together to form a 4- to 7-membered ring, which may contain a heteroatom selected from N, O, and S as a ring-constituting atom other than the N atom to which R5 binds, provided the ring is not a heteroaryl, together with the N atom to which R5 binds, X represents O or CH2, Y represents C═O, C(═O)O, C(═O)NR7, SO2, or a bond, wherein R7 represents hydrogen, C1-6 alkyl, aralkyl in which the aryl moiety has 6 to 10 carbon atoms and the alkylene moiety has 1 to 5 carbon atoms, heteroarylalkyl in which the heteroaryl contains 1 to 4 heteroatoms selected from N, O, and S as a ring-constituting atom and the alkylene moiety has 1 to 5 carbon atoms, or cycloalkylalkyl in which the cycloalkyl moiety has 3 to 6 carbon atoms and the alkylene moiety has 1 to 5 carbon atoms, or the N atom to which R7 binds and R1 may combine together to form a 4- to 7-membered ring which may contain a heteroatom selected from N, O, and S as a ring-constituting atom other than the N atom to which R7 binds, and m and n, which are the same or different, represent an integer of 0 to 2, provided that m and n are not 0 at the same time, wherein the C1-6 alkyl of R1, R4, R5, and R6, the 4- to 7-membered ring formed by R5 and R6, and the 4- to 7-membered ring formed by R5 and R4 may be substituted with a hydroxy group, and the aryl moiety of the C6-10 aryl and the aralkyl in which the aryl moiety has 6 to 10 carbon atoms and the alkylene moiety has 1 to 5 carbon atoms of R1, and the heteroaryl moiety of the heteroaryl containing 1 to 4 heteroatoms selected from N, O, and S as a ring-constituting atom, and the heteroarylalkyl in which the heteroaryl contains 1 to 4 heteroatoms selected from N, O, and S as a ring-constituting atom and the alkylene moiety has 1 to 5 carbon atoms of R1, may be substituted with at least one substituent selected from C1-6 alkyl, C1-6 alkoxy, C1-6 alkanoyloxy, hydroxy, alkoxycarbonyl in which the alkoxy moiety has 1 to 6 carbon atoms, carbamoyl, alkylcarbamoyl in which the alkyl moiety has 1 to 6 carbon atoms, dialkylcarbamoyl in which each alkyl moiety has 1 to 6 carbon atoms, halogen, nitro, cyano, C1-6 alkyl substituted with 1 to 3 halogens, C1-6 alkoxy substituted with 1 to 3 halogens, phenyl, heteroaryl containing 1 to 4 heteroatoms selected from N, O, and S as a ring-constituting atom, phenoxy, phenylalkyl in which the alkyl moiety has 1 to 3 carbon atoms, methylenedioxy, and NR8R9, wherein R8 and R9 independently represent hydrogen, C1-6 alkyl, C2-6 alkenyl, C3-6 cycloalkyl, C1-6 alkanoyl, or alkoxycarbonyl in which the alkoxy moiety has 1 to 6 carbon atoms, or R8 and R9 may form, together with the N atom to which they bind, a 4- to 7-membered ring which may further contain a heteroatom selected from N, O, and S. |
