Therapeutic agent or prophylactic agent for amyotrophic lateral sclerosis

A method of treating amyotrophic lateral sclerosis, comprising:

• administering to a patient in need thereof, a therapeutic amount of a tetrahydroquinoline derivative represented by general formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient,
• wherein
• R1x is hydrogen, aryl, or 5- or 6-membered heteroaryl having one or two heteroatoms selected from nitrogen, oxygen, and sulfur atoms (any one or two hydrogen atoms in the aryl or the 5- or 6-membered heteroaryl are each independently optionally replaced by a halogen atom(s), a C1-C3 alkyl in which any one to three hydrogen atoms are each independently optionally replaced by a hydroxy group(s) or a fluorine atom(s), C1-C3 alkoxy in which any one to three hydrogen atoms are optionally replaced by a fluorine atom(s), cyano, methoxycarbonyl, —CONR6R7, —NHCOR8, aminosulfonyl, C1-C3 alkylsulfonylamino, aminosulfonylamino, or C1-C3 alkylsulfonyl group(s)), or
• in cases where the aryl group is phenyl, R1x is optionally a fused ring group formed by fusing of the phenyl group and one ring selected from the group consisting of 5- or 6-membered lactam rings and 5- or 6-membered saturated heterocycles each containing one or two oxygen atoms as the atom constituting the ring (any one hydrogen atom in the fused ring group is optionally replaced by a methyl group);
• R1y is hydrogen, phenyl, 4-hydroxymethylphenyl, 4-aminocarbonylphenyl, 4-acetamidophenyl, 4-aminosulfonylphenyl, 4-methylsulfonylphenyl, or 3-pyridyl (except that both R1x and R1y represent hydrogen);
• for the combination of R2, R4, and R5, all of R2, R4, and R5 represent hydrogen, or
• one of R2, R4, and R5 is halogen, methoxy, or methyl in which one hydrogen atom is optionally replaced by a hydroxy group, and the other two are hydrogen;
• R3 is hydrogen, halogen, C1-C3 alkyl in which any one to three hydrogen atoms are each independently optionally replaced by a hydroxy group(s) or a fluorine atom(s), 3-hydroxyoxetan-3-yl, hydroxy, C1-C3 alkoxy in which any one to three hydrogen atoms are optionally replaced by a fluorine atom(s), methoxycarbonyl, —NR9R10, —CH2NR11R12, or —CH2CONR13R14;
• R6 and R7 each independently represent hydrogen or C1-C3 alkyl, or
• R6 and R7 together represent —(CH2)h—;
• h is an integer of 3 to 5, wherein any one of the methylene groups is optionally replaced by an oxygen atom, —NH—, or —N(CH3)—;
• R8 is hydrogen or C1-C3 alkyl;
• R9 and R10 each independently represent hydrogen, —COR15, or C1-C3 alkylsulfonyl, or
• R9 and R10 together represent —(CH2)n—;
• n is an integer of 3 to 6;
• R11 and R12 together represent —(CH2)m—;
• m is an integer of 3 to 5, wherein any one of the methylene groups is optionally replaced by an oxygen atom;
• R13 and R14 each independently represent hydrogen, C1-C5 alkyl group, 2-hydroxyethyl, C3 or C4 cycloalkyl in which any one carbon atom is optionally replaced by an oxygen atom, or methyl which is substituted with a C3 or C4 cycloalkyl group in which any one carbon atom is optionally replaced by a nitrogen or oxygen atom, or
• R13 and R14 together represent —(CH2)k— in which any one or two hydrogen atoms are optionally replaced by a fluorine atom(s), a methyl group(s), a hydroxy group(s), or a methoxy group(s) or in which any one CH2 group is optionally replaced by an oxygen atom, a nitrogen atom, or —CONH—;
• k is an integer of 3 to 5;
• R15 is C1-C5 alkyl, C1-C5 alkoxy, or —NHR16;
• R16 is hydrogen or C1-C5 alkyl;
• or
• Rv is hydrogen, methyl in which any one hydrogen atom is optionally replaced by a hydroxy or methoxycarbonyl group, or methoxycarbonyl;
• and
• Rw is hydrogen, methyl, hydroxymethyl, or methoxycarbonyl.