Compound; tautomer and geometric isomer thereof; salt of said compound, tautomer, or geometric isomer; method for manufacturing said compound, tautomer, isomer, or salt; antimicrobial agent; and anti-infective drug
The present invention provides compounds belonging to 3-acyloxyindole compounds or 3-acyl-4-hydroxycoumarin compounds, a tautomer or geometric isomer thereof, or a salt thereof and methods for producing the same, which compounds are useful as antibacterial agent and as therapeutic drugs against infectious diseases.
1. A compound represented by any one of General Formulas (1) to (2) below, a tautomer or geometric isomer thereof, or a salt thereof:
wherein
X 1 represents a single bond or an alkylene group having 1 to 8 carbon atoms,
Y 1 represents a single bond, —O—, —NHCO—, —NHCOO—, —S—, —SO—, or —SO 2 —,
Z 1 represents a cyclic, linear, or branched alkyl group which has 8 to 30 carbon atoms and may have a halogen atom,
X 2 represents a single bond, —CO—, —CONH—, or —COO—,
Y 2 represents a hydrocarbon group which has 1 to 30 carbon atoms and may have —CN, —NO 2 , an alkoxy group, a halogen atom, or any combination thereof; or a hydrogen atom,
X 3 represents a single bond or —NH—,
Z represents a hydrogen atom, a halogen atom, an alkoxy group having 1 to 6 carbon atoms, or a hydrocarbon group having 1 to 20 carbon atoms, and
R 1 represents a hydrocarbon group which has 1 to 30 carbon atoms and may have an alkoxy group, —OH, —CN, —NO 2 , a halogen atom, or any combination thereof.
2. The compound, the tautomer or geometric isomer thereof, or the salt thereof according to claim 1 , wherein X 1 is a methylene group, X 2 is —CO— or —CONH—, X 3 is a single bond, Y 1 is —O—, Y 2 is a methyl group, or a phenyl group which may have, as a substituent, an alkoxy group, a trifluoromethyl group, a halogen atom, or any combination thereof, Z is a hydrogen atom or a halogen atom, and Z 1 is a cyclic, linear, or branched alkyl group having 8 to 12 carbon atoms.
3. The compound, the tautomer or geometric isomer thereof, or the salt thereof according to claim 1 , wherein X 1 is a methylene group, X 2 is —CO— or —CONH—, X 3 is a single bond, Y 1 is —S—, Y 2 is a methyl group, or a phenyl group which may have, as a substituent, an alkoxy group, a trifluoromethyl group, a halogen atom, or any combination thereof, Z is a hydrogen atom or a halogen atom, and Z 1 is a cyclic, linear, or branched alkyl group having 8 to 12 carbon atoms.
4. The compound, the tautomer or geometric isomer thereof, or the salt thereof according to claim 1 , wherein X 1 , X 3 , and Y 1 each are a single bond, X 2 is —CO— or —CONH—, Y 2 is a methyl group, or a phenyl group which may have, as a substituent, an alkoxy group, a trifluoromethyl group, a halogen atom, or any combination thereof, Z is a hydrogen atom or a halogen atom, and Z 1 is a cyclic, linear, or branched alkyl group having 8 to 12 carbon atoms.
5. A method for producing a compound represented by any one of General Formulas (1) to (2) below, a tautomer or geometric isomer thereof, or a salt thereof,
wherein
X 1 represents a single bond or an alkylene group having 1 to 8 carbon atoms,
Y 1 represents a single bond, —O—, —NHCO—, —NHCOO—, —S—, —SO—, or —SO 2 —,
Z 1 represents a cyclic, linear, or branched alkyl group which has 8 to 30 carbon atoms and may have a halogen atom,
X 2 represents a single bond, —CO—, —CONH—, or —COO—,
Y 2 represents a hydrocarbon group which has 1 to 30 carbon atoms and may have —CN, —NO 2 , an alkoxy group, a halogen atom, or any combination thereof; or a hydrogen atom,
X 3 represents a single bond or —NH—,
Z represents a hydrogen atom, a halogen atom, an alkoxy group having 1 to 6 carbon atoms, or a hydrocarbon group having 1 to 20 carbon atoms, and
R 1 represents a hydrocarbon group which has 1 to 30 carbon atoms and may have an alkoxy group, —OH, —CN, —NO 2 , a halogen atom, or any combination thereof,
the method comprising:
mixing and reacting an oxyindole compound represented by General Formula (6) or (7) below with a carboxylic acid in an organic solvent in the presence of a condensation agent and an amine base,
wherein,
Z 1 represents a cyclic, linear, or branched alkyl group which has 8 to 30 carbon atoms and may have a halogen atom,
X 2 represents a single bond, —CO—, —CONH—, or —COO—,
Y 2 represents a hydrocarbon group which has 1 to 30 carbon atoms and may have —CN, —NO 2 , an alkoxy group, a halogen atom, or any combination thereof; or a hydrogen atom,
X 3 represents a single bond or —NH—, and
Z represents a hydrogen atom, a halogen atom, an alkoxy group having 1 to 6 carbon atoms, or a hydrocarbon group having 1 to 20 carbon atoms.
6. A method for producing a compound represented by any one of General Formulas (1) to (2), below, a tautomer or geometric isomer thereof, or a salt thereof:
wherein
X 1 represents a single bond or an alkylene group having 1 to 8 carbon atoms,
Y 1 represents a single bond, —O—, —NHCO—, —NHCOO—, —S—, —SO—, or —SO 2 —,
Z 1 represents a cyclic, linear, or branched alkyl group which has 8 to 30 carbon atoms and may have a halogen atom,
X 2 represents a single bond, —CO—, —CONH—, or —COO—,
Y 2 represents a hydrocarbon group which has 1 to 30 carbon atoms and may have —CN, —NO 2 , an alkoxy group, a halogen atom, or any combination thereof; or a hydrogen atom,
X 3 represents a single bond or —NH—,
Z represents a hydrogen atom, a halogen atom, an alkoxy group having 1 to 6 carbon atoms, or a hydrocarbon group having 1 to 20 carbon atoms, and
R 1 represents a hydrocarbon group which has 1 to 30 carbon atoms and may have an alkoxy group, —OH, —CN, —NO 2 , a halogen atom, or any combination thereof,
the method comprising:
mixing and reacting an oxyindole compound represented by General Formula (6) or (7) below with a carboxylic acid chloride in an organic solvent in the presence of an amine base,
wherein
Z 1 represents a cyclic, linear, or branched alkyl group which has 8 to 30 carbon atoms and may have a halogen atom,
X 2 represents a single bond, —CO—, —CONH—, or —COO—,
Y 2 represents a hydrocarbon group which has 1 to 30 carbon atoms and may have —CN, —NO 2 , an alkoxy group, a halogen atom, or any combination thereof; or a hydrogen atom,
X 3 represents a single bond or —NH—, and
Z represents a hydrogen atom, a halogen atom, an alkoxy group having 1 to 6 carbon atoms, or a hydrocarbon group having 1 to 20 carbon atoms.
7. A method for producing a compound represented by any one of General Formulas (1) to (2) below, a tautomer or geometric isomer thereof, or a salt thereof,
wherein
X 1 represents a single bond or an alkylene group having 1 to 8 carbon atoms,
Y 1 represents a single bond, —O—, —NHCO—, —NHCOO—, —S—, —SO—, or —SO 2 —,
Z 1 represents a cyclic, linear, or branched alkyl group which has 8 to 30 carbon atoms and may have a halogen atom,
X 2 represents a single bond, —CO—, —CONH—, or —COO—,
Y 2 represents a hydrocarbon group which has 1 to 30 carbon atoms and may have —CN, —NO 2 , an alkoxy group, a halogen atom, or any combination thereof; or a hydrogen atom,
X 3 represents a single bond or —NH—,
Z represents a hydrogen atom, a halogen atom, an alkoxy group having 1 to 6 carbon atoms, or a hydrocarbon group having 1 to 20 carbon atoms, and
R 1 represents a hydrocarbon group which has 1 to 30 carbon atoms and may have an alkoxy group, —OH, —CN, —NO 2 , a halogen atom, or any combination thereof,
the method comprising:
mixing and reacting an oxyindole compound represented by General Formula (6) or (7) below with a carboxylic anhydride in an organic solvent in the presence of an amine base,
wherein
Z 1 represents a cyclic, linear, or branched alkyl group which has 8 to 30 carbon atoms and may have a halogen atom,
X 2 represents a single bond, —CO—, —CONH—, or —COO—,
Y 2 represents a hydrocarbon group which has 1 to 30 carbon atoms and may have —CN, —NO 2 , an alkoxy group, a halogen atom, or any combination thereof; or a hydrogen atom,
X 3 represents a single bond or —NH—, and
Z represents a hydrogen atom, a halogen atom, an alkoxy group having 1 to 6 carbon atoms, or a hydrocarbon group having 1 to 20 carbon atoms.
8. An antibacterial agent, comprising:
a compound, represented by any one of General Formulas (1) to (2) below, a tautomer or geometric isomer thereof, or a salt thereof:
wherein,
X 1 represents a single bond or an alkylene group having 1 to 8 carbon atoms,
Y 1 represents a single bond, —O—, —NHCO—, —NHCOO—, —S—, —SO—, or —SO 2 —,
Z 1 represents a cyclic, linear, or branched alkyl group which has 8 to 30 carbon atoms and may have a halogen atom,
X 2 represents a single bond, —CO—, —CONH—, or —COO—,
Y 2 represents a hydrocarbon group which has 1 to 30 carbon atoms and may have —CN, —NO 2 , an alkoxy group, a halogen atom, or any combination thereof; or a hydrogen atom,
X 3 represents a single bond or —NH—,
Z represents a hydrogen atom, a halogen atom, an alkoxy group having 1 to 6 carbon atoms, or a hydrocarbon group having 1 to 20 carbon atoms, and
R 1 represents a hydrocarbon group which has 1 to 30 carbon atoms and may have an alkoxy group, —OH, —CN, —NO 2 , a halogen atom, or any combination thereof.
9. An infectious disease therapeutic drug, comprising:
an antibacterial agent wherein the antibacterial agent comprises:
a compound represented by any one of General Formulas (1) to (2) below, a tautomer or geometric isomer thereof, or a salt thereof,
wherein,
X 1 represents a single bond or an alkylene group having 1 to 8 carbon atoms,
Y 1 represents a single bond, —O—, —NHCO—, —NHCOO—, —S—, —SO—, or —SO 2 —,
Z 1 represents a cyclic, linear, or branched alkyl group which has 8 to 30 carbon atoms and may have a halogen atom,
X 2 represents a single bond, —CO—, —CONH—, or —COO—,
Y 2 represents a hydrocarbon group which has 1 to 30 carbon atoms and may have —CN, —NO 2 , an alkoxy group, a halogen atom, or any combination thereof; or a hydrogen atom,
X 3 represents a single bond or —NH—,
Z represents a hydrogen atom, a halogen atom, an alkoxy group having 1 to 6 carbon atoms, or a hydrocarbon group having 1 to 20 carbon atoms, and
R 1 represents a hydrocarbon group which has 1 to 30 carbon atoms and may have an alkoxy group, —OH, —CN, —NO 2 , a halogen atom, or any combination thereof.