Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1992-01-17
1994-06-28
Waddell, Frederick E.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
546156, C07D215233, A01K 3147
Patent
active
053247353
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a novel quinolone carboxylic acid derivative and a salt thereof which have excellent antimicrobial activity, to an antimicrobial agent comprising the same as an effective component, and to an intermediate for producing the same.
DESCRIPTION OF THE BACKGROUND
Synthetic antimicrobial agents such as nalidixic acid, piromidic acid, and the like are known as drugs for curing infectious diseases caused by Gram negative microorganisms. They exhibit, however, only deficient effects on intractable diseases such as pseudomoniasis and the like. On the other hand, antimicrobial agents with a stronger antimicrobial activity, such as norfloxacin, ofloxacin, and the like, have been developed and clinically used.
In order for an antimicrobial agent to effectively exhibit its action, the agent must have a strong antimicrobial activity and must be efficiently utilized. The above-mentioned conventional synthetic antimicrobial agents had a defect in that they are insufficiently absorbed, thus achieving only low utilization by living bodies.
In view of such a situation, the present inventors have synthesized a number of quinolone carboxylic acid derivatives and studied their antimicrobial activity and absorption efficiency by living bodies, and found that quinolone carboxylic acid derivatives of the following formula (I) and their salts exhibited excellent antimicrobial activities and superior absorptivity. Such a finding has led to the completion of the present invention.
DISCLOSURE OF THE INVENTION
An object of the present invention is to provide a quinolone carboxylic acid derivative having the following formula (I), ##STR3## wherein R.sub.1 is a lower alkyl group, R.sub.2 is a hydrogen atom or a lower alkyl group, R.sub.3 is a hydrogen atom or a halogen R.sub.4 and R.sub.5 together form a five- or six-membered ring which may contain hetero atoms or may have substituents, provided that a compound wherein R.sub.1 is methyl group R.sub.2 and R.sub.3 are hydrogen atoms and ##STR4## is a piperazinyl group is excluded; or a salt thereof; to an antimicrobial agent comprising the same as an effective component; and to an intermediate for producing the same.
In the present invention, groups represented by ##STR5## include piperazinyl, pyrrolidinyl, morpholino, and lower alkyl groups, hydroxy groups, amino groups, amino-lower-alkyl groups, are given as examples of the substituents.
In the present invention, an alkyl group is normally means a linear or branched alkyl group having 1-6 carbon atoms, specifically, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, n-pentyl, n-hexyl, or the like. Examples given of halogen atoms are chlorine, bromine, iodine, fluorine.
The salts of the compounds of formula (I) of the present invention are not specifically limited so long as they are physiologically acceptable salts, and include salts of alkali metal, alkaline earth metal, inorganic acid, organic acid, and the like. Specific examples which can be given as salts of alkali metal are lithium salt, sodium salt, potassium salt, and the like; as salts of inorganic acids are hydrochloride, sulfate, nitrate, hydrobromide, phosphate, and the like; and as salts of organic acid are acetate, fumarate, maleate, lactate, citrate, tartrate malate, oxalate, methanesulfonate, benzenesulfonate, and the like.
The compounds of the present invention may have an asymmetric carbon atom depending the type of the group ##STR6##
The present invention include both the optical isomers and mixtures thereof.
The compound of formula (I) of the present invention can be prepared by one of the following processes. ##STR7## wherein R.sub.2-1 is a lower alkyl group, X is a halogen atom, R.sub.1, R.sub.3, R.sub.4, and R.sub.5, are the same as those previously defined.
According to the above process, compound (II) is halogenized into compound (III), which is reacted with an amine (IV) to produce compound (V). Compound (V) is then dehydrohalogenized and hydrolyzed to give compound (I) or its salt of this
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Remuzon et al. J. Med. Chem. 34 (1). 1991. pp. 29-37.
Journal of Medicinal Chemistry, vol. 32, 1989, pp. 537-542, D. Bouzard, et al., "Fluoronaphthyridines and Quinolones as Antibacterial Agents. 1. Synthesis and Structure-Activity Relationships of New 1-Substituted Derivatives".
Chemical Abstracts, vol. 109, 1988, pp. 381, 51554k, Y. Nishimura, et al., "Pyridonecarboxylic Acids as Antibacterial Agents. xxi. Synthesis and Antibacterial Activity of Enoxacin Analogs with a Variant at Position 1".
Asaoka Takemitsu
Katori Tatsuhiko
Kawahara Ryuichi
Kuraishi Tadayuki
Matsuda Hideaki
Spivack Phyllis G.
SS Pharmaceutical Co., Ltd.
Waddell Frederick E.
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