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

Patent metadata

Field	Value
Publication number	US-9512075-B2
Application number	US-201314436316-A
Country	US
Kind code	B2
Filing date	Oct 17, 2013
Priority date	Oct 17, 2012
Publication date	Dec 6, 2016
Grant date	Dec 6, 2016

Abstract

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.

First claim

The invention claimed is:

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 at

Assignees

• Univ Okayama
• Microbial Chem Res Found
• Univ Kinki

Inventors

• Ishikawa Teruhiko
• Kitaoka Tatsuya
• Katayama Shyota
• Itoh Yoshikuni
• Utsumi Ryutaro
• Igarashi Masayuki

Classifications

• A61P31/04

  Antibacterial agents · CPC title

• C07D311/56

  without hydrogen atoms in position 3 · CPC title

• C07D209/34 Primary

  in position 2 · CPC title