Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1992-06-08
1995-02-14
Rizzo, Nicholas
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
540222, C07D50122, A61K 31545
Patent
active
053896254
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to novel cephalosporin compounds which are useful for the prophylaxis and treatment of bacterial infectious diseases and are noticeably sweet, and to methods for producing same. More specifically, the present invention relates to cephalosporin compounds which are excellent in absorption from the digestive tract, show a wide range of antimicrobial activities in the body after being absorbed from the digestive tract, and have 10-400 times greater sweetness than sucrose, to their pharmaceutically acceptable salts, and to methods for producing them.
BACKGROUND ART
In general, cephalosporin compounds are poor in absorption from digestive tract, and therefore, are usually administered by injection. For example, there have been known cephalosporin compounds which have a wide range of excellent antimicrobial activities and are represented by the following formula (A) ##STR2## wherein R.sup.1 is hydrogen atom or lower alkyl, and salts thereof [hereinafter the compounds encompassed in formula (A) including known compounds are referred to as Compound (A)]. However, said Compound (A) is also poor in absorption from digestive tract, rendering administration by injections inevitable.
Although various attempts to introduce a liposoluble ester residue into the 4-position carboxylic acid of Compound (A) to improve absorption from the digestive tract, and to produce compounds capable of converting into Compound (A) by decomposition upon absorption into blood are currently in progress, such compounds are all unsatisfactory since they permit no improvement in absorption from the digestive tract and show inconsistent absorption due to their poor solubility in water. In addition, the compounds obtained as a result of such attempts are generally poor in taste, particularly bitter, making formulation of pharmaceutical preparations easily taken very difficult.
DISCLOSURE OF THE INVENTION
The object of the present invention is to provide cephalosporin compounds having good solubility in water, easily absorbed from digestive tract, extremely good in taste (sweet), and capable of exerting excellent antimicrobial activities of Compound (A) in the body, which can be obtained by chemically modifying Compound (A).
The present inventors have conducted various investigations for the purpose of producing cephalosporin compounds, wherein the basic structure is formula (A), which allow absorption from digestive tract by oral administration, and found that the cephalosporin compounds of the following formula (I) and salts thereof are soluble in water and markedly superior in absorption from digestive tract, that upon absorption, they are converted into Compound (A) or salt thereof in blood, and high concentration of the Compound (A) or salt thereof in blood lasts for a long period, and that said compounds have extremely strong sweetness; with these findings, the present inventors further developed and completed the present invention.
That is, the present invention relates to cephalosporin compounds of the formula (I) ##STR3## wherein R.sup.1 is hydrogen atom or lower alkyl, and R.sup.2 is 1-alkanoyloxyalkyl or 1-alkoxycarbonyloxyalkyl [hereinafter sometimes referred to as Compound (I)], pharmaceutically acceptable salts thereof, and methods for producing them.
In the present specification, each symbol stands for the following.
As regards R.sup.1, lower alkyl may be straight- or branched-chain, and preferably exemplified by those having 1 to 4, particularly 1 to 3 carbon atoms such as methyl, ethyl, propyl, isopropyl and cyclopropyl.
As regards R.sup.2, the alkanoyl moiety of 1-alkanoyloxyalkyl has 2 to 10, preferably 2 to 7 carbon atoms, and the alkyl moiety has 1 or 2 carbon atoms. Such group includes, for example, acetoxymethyl, propionyloxymethyl, iso-propionyloxymethyl, n-butyryloxymethyl, iso-butyryloxymethyl, pivaloyloxymethyl, n-valeryloxymethyl, 2-methylbutyryloxymethyl, isovaleryloxymethyl, n-hexanoyloxymethyl, 3-methylvaleryloxymethyl, neohexanoyloxymethyl, 2-methylhexanoyloxymethy
REFERENCES:
patent: 4477447 (1984-10-01), Ueda et al.
Hatano Satoru
Kakeya Nobuharu
Kasai Masayasu
Muro Hiroyuki
Nishimura Ken-ichi
Kyoto Pharmaceutical Industries, Ltd.
Rizzo Nicholas
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