Phosphonic diester derivatives

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...

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540542, 544 92, 544244, A61K 31675, C07F 96512

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active

056249187

DESCRIPTION:

BRIEF SUMMARY
This application is a National Phase filling of PCT/JP94/00883, which was filed in the International Phase May 31, 1994.


TECHNICAL FIELD

The present invention relates to novel phosphonic diester derivatives.


PRIOR ART

The phosphonic diester derivatives of the invention are novel compounds not heretofore described in the literature.
The object of the invention is to provide compounds of value as medicines as will be described hereinafter.


DISCLOSURE OF THE INVENTION

The present invention provides a phosphonic diester derivative of the following general formula (1): ##STR2## wherein A represents an oxygen atom or a sulfur atom; R.sup.1, R.sup.2, R.sup.9 and R.sup.10 are the same or different and they each represent a hydrogen atom, a lower alkoxy group, a nitro group, a lower alkyl group, a halogen-substituted lower alkyl group or a halogen atom; R.sup.3 represents a phenyl group, --B--R.sup.6 (wherein B represents an oxygen atom or a sulfur atom and R.sup.6 represents a hydrogen atom, a lower alkyl group, a cycloalkyl group, a phenyl group, a phenyl(lower)alkyl group optionally having a halogen atom as a substituent on the phenyl ring, a phenoxy(lower)alkyl group, a lower alkoxycarbonyl(lower)alkyl group, a carboxy(lower)alkyl group or a lower alkenyl group) or --NR.sup.7 R.sup.8 (wherein R.sup.7 and R.sup.8 are the same or different and they each represent a hydrogen atom, a lower alkyl group, an amino group or a cycloalkyl group or combinedly represent a lower alkylene group); and R.sup.4 and R.sup.5 are the same or different and they each represent a hydrogen atom or a lower alkyl group.
Each of the groups relevant to the above general formula (1) includes the following exemplary species.
The lower alkyl group includes straight- or branched-chain lower alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl and so on.
The cycloalkyl group includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and so on.
The lower alkoxy group includes methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy and so on.
The phenyl(lower)alkyl group optionally having a halogen atom as a substituent on the phenyl ring includes benzyl, .alpha.-phenetyl, .beta.-phenetyl, 3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl, 6-phenylhexyl, 2-bromobenzyl, 2-fluorobenzyl, 2-chlorobenzyl, 2-iodobenzyl, 3-bromobenzyl, 3-fluorobenzyl, 3-chlorobenzyl, 3-iodobenzyl, 4-bromobenzyl, 4-fluorobenzyl, 4-chlorobenzyl, 4-iodobenzyl, 4-bromo-3-fluorobenzyl, 4-bromo-2-fluorobenzyl, 3-bromo-4-fluorobenzyl, 2-bromo-4-fluorobenzyl, 4-bromo-3-chlorobenzyl, 4-bromo-2-chlorobenzyl, 3-bromo-4-chlorobenzyl, 2-bromo-4-chlorobenzyl, 4-bromo-3-iodobenzyl, 4-bromo-2-iodobenzyl, 3-bromo-4-iodobenzyl, 2-bromo-4-iodobenzyl, 4-bromo-3-fluoro-.alpha.-phenetyl, 4-bromo-3-fluoro-.beta.-phenetyl, 3-(4-bromo-3-fluorophenyl)propyl, 4-(4-bromo-2-fluorophenyl)butyl, 5-(4-bromo-3-fluorophenyl)pentyl, 6(4-bromo-2-fluorophenyl)hexyl and so on.
The phenoxy(lower)alkyl group includes phenoxymethyl, 2-phenoxyethyl, 3-phenoxylpropyl, 4-phenoxybutyl, 5-phenoxypentyl, 6-phenoxyhexyl and so on.
The lower alkylene group includes methylene, ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene and so on.
The halogen-substituted lower alkyl group includes chloromethyl, bromomethyl, fluoromethyl, iodomethyl, dichloromethyl, dibromomethyl, difluoromethyl, diiodomethyl, trichloromethyl, tribromomethyl, trifluoromethyl, triiodomethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 3-bromopropyl, 4,4-dichlorobutyl, 5,5,5-trifluoropentyl, 6-iodohexyl and so on.
The lower alkoxycarbonyl(lower)alkyl group includes methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, butoxycarbonylmethyl, pentyloxycarbonylmethyl, hexyloxycarbonylmethyl, 1-(methoxycarbonyl)ethyl, 2-(methoxycarbonyl)ethyl, 3-(methoxycarbonyl)propyl, 4-(methoxycarbonyl)butyl, 5-(methoxycarbonyl)pentyl, 6-(methoxycarbonyl)hexyl, 1-(ethoxycarbonyl)ethyl, 2-(ethoxycarbonyl)ethyl, 3-(ethoxycarbonyl)propyl, 4-(ethoxycarbonyl)butyl, 5-(et

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