Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1994-01-26
1997-12-09
Ivy, C. Warren
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514312, 546156, 546123, A61K 3147, A61K 3150, C07D215233, C07D24104
Patent
active
056961324
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/JP92/00687, filed May, 27, 1992.
FIELD OF THE INVENTION
This invention relates to an antimicrobial compound useful as human and veterinary drugs, fish drugs, and antimicrobial preservatives, and an antimicrobial agent containing the compound as an active ingredient.
BACKGROUND OF THE INVENTION
Quinolone derivatives are known as synthetic antimicrobial agents having a condensed pyridonecarboxylic acid skeleton. It is known that those having a cyclopropyl group at the 1-position exhibit potent antimicrobial activity. Further, quinolone derivatives having a fluorine atom introduced into the 2-position of the cyclopropyl group in a cis-configuration with respect to the condensed pyridonecarboxylic acid moiety also exhibit potent antimicrobial activity. These quinolone derivatives are considered to have not only potent antimicrobial activity but high safety (see JP-A-62-12760, the term "JP-A" means an "unexamined published Japanese patent application").
Quinolone derivatives having a cis-halogenocyclopropyl group at the 1-position possess excellent properties in terms of antimicrobial activity and safety. These quinolone derivatives embrace a pair of enantiomers attributed to the halogenocyclopropane ring even when the substituent at the other position includes no stereoisomerism, which is ascribed to the stereochemical relationship between the pyridonecarboxylic acid moiety and the halogen atom on the cyclopropane ring. It is possible to apply a racemic compound, a mixture of enantiomers, as a drug as such.
When stereoisomerism exists at a position other than the halogenocyclopropane ring, particularly at the 7-positioned substituent, such quinolone derivatives include diastereomers, that is, at least 4 kinds of stereoisomers. A mixture of diastereomers is a mixture of isomers having different physical properties and is difficult to apply as a drug as such.
The present inventors have conducted extensive investigations for the purpose of obtaining a 1-(1,2-cis-2-fluorocyclopropyl)-substituted quinolone compound which consists of a single isomer even if it may embrace diastereomers.
As a result, the inventors have succeeded in separately obtaining each enantiomer of cis-2-fluorocyclopropylamine as a pure isomer and then separately obtaining each enantiomer of a quinolone derivative attributed only to the stereochemical configuration of the fluorocyclopropane ring thereof by starting with the cis-fluorocyclopropylamine.
Now that the above-mentioned quinolone derivative useful as an intermediate has been obtained, it is possible to synthesize an optically active quinolone derivative consisting solely of a single diastereomer by reacting the quinolone derivative with a saturated nitrogen-containing heterocyclic compound consisting solely of a single isomer at the time of introducing a saturated nitrogen-containing heterocyclic substituent into the 7-position.
And the inventors have ascertained that each of the resulting diastereomers exhibits potent antimicrobial activity and also has high safety with markedly improved selective toxicity and thus completed the present invention.
DISCLOSURE OF THE INVENTION
The present invention relates to a compound represented by formula (I): ##STR2## wherein R.sup.1 represents a methyl group, an ethyl group, a propyl group, an isopropyl group, a fluoromethyl group or a difluoromethyl group; R.sup.2 represents a substituted or unsubstituted saturated nitrogen-containing heterocyclic substituent which may contain an oxygen atom, a sulfur atom or more than one nitrogen atoms as a ring-constituent atom; A represents C--X.sup.3 or a nitrogen atom; X.sup.1 and X.sup.2 each represents a halogen atom; X.sup.3 represents a hydrogen atom, a halogen atom, a cyano group, a trifluoromethyl group, an alkyl group having from 1 to 6 carbon atoms or an alkyloxy group having from 1 to 6 carbon atoms; and Z represents a phenylalkyl group composed of an alkylene group having from 1 to 6 carbon atoms and a phenyl group, a hydrogen atom, a phenyl group, an ace
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Hayakawa Isao
Kimura Youichi
Takahashi Hisashi
Daiichi Pharmaceutical Co. Ltd.
Ivy C. Warren
M. Mach D. Margaret
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