Cephem compounds and pharmaceutical use thereof

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...

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Details

540224, 540225, 540226, 540227, A61K 31546, A61P 3104, C07D50159

Patent

active

061503517

DESCRIPTION:

BRIEF SUMMARY
FIELD OF THE INVENTION

This invention relates to new cephem compounds and pharmaceutically acceptable salt thereof.
More particularly, it relates to new cephem compounds and salts thereof, which have antimicrobial activity against Helicobacter pylori, to a pharmaceutical composition comprising said cephem compound or a pharmaceutically acceptable salt thereof and to a method for the prophylaxis and/or treatment of ulcer and the prophylaxis of stomach cancer in human being and animals.


BACKGROUND ART

At present, acid secretion inhibitors such as H.sub.2 -blocker and proton pump inhibitor, and mucosalprotective factor enhancers, have been mainly used for the treatment of peptic ulcers such as gastric ulcer and duodenal ulcer. While the use of H.sub.2 -blocker and proton pump inhibitor shortens treatment period, the problem of possible recurrence of the disease still remains to be solved.
Helicobacter pylori (H. pylori) is a Gram negative bacterium found in the mucous layer on the gastric epithelium of humans, and infection with H. pylori has been found to induce gastrointestinal diseases, such as chronic gastritis and peptic ulcer (e.g., gastric ulcer and duodenal ulcer). There are an increasing number of reports on the effectiveness of the eradication of H. pylori for treating intractable ulcers and prevention of ulcer recurrence. The drug having an antimicrobial action on H. pylori is useful for the treatment and/or prevention of gastritis and ulcer, and a new drug having such pharmacological action is desired.


DISCLOSURE OF THE INVENTION

One object of this invention is to provide new cephem compounds and salts thereof, which have antimicrobial activity against Helicobacter pylori.
The cephem compounds and salts thereof are useful as anti-Helicobacter pylori agents, anti-gastritis agents, anti-ulcer agents and anti-cancer agents. The cephem compounds and salts thereof may be used as anti-Helicobacter pylori agents, anti-gastritis agents, anti-ulcer agents and anti-cancer agents in combination with an acid secretion inhibitor such as an H.sub.2 -blocker and a proton pump inhibitor.
A further object of this invention is to provide a pharmaceutical composition for the prophylactic and/or therapeutic treatment of diseases caused by Helicobacter pylori infection in human being or animals, comprising, as an active ingredient, said cephem compound or a pharmaceutically acceptable salt thereof.
A further object of this invention is to provide a therapeutical method for the prophylaxis and/or treatment of the diseases caused by Helicobacter pylori infection such as gastritis, ulcer [e.g. peptic ulcer (e.g. gastric ulcer, duodenal ulcer, anastomotic ulcer, etc.), etc.], MALT lymphoma, non-ulcer dyspepsia, and stomach cancer in human being and animals.
The cephem compounds in the present invention can be represented by the following general formula (I): ##STR2## wherein R.sup.1 is aryl(lower)alkyl which may have 1 to 3 suitable substituent(s) selected from the group consisting of lower alkyl which may form a ring together with the carbon atom said lower alkyl is attached to, hydroxy and halogen; selected from the group consisting of lower alkenyl, lower alkylidene, halogen, amino and protected amino; or selected from the group consisting of acyl(lower)alkyl, hydroxy(lower)alkyl, mono or di(lower)alkylamino(lower)alkyl, amino(lower)alkyl, protected amino(lower)alkyl, acyl, acylamino and aryl having carboxy, in which heterocyclic group may have additionally lower alkyl; or and lower alkyl, then R.sup.3 is acyloxy(lower)alkoxycarbonyl, thiadiazolyl having lower alkyl, thiadiazolyl having lower alkyl.
The cephem compound (I) or a salt thereof can be prepared by processes as illustrated in the following reaction schemes. ##STR3##
The starting compounds (II) and (IV) or a salt thereof can be prepared by processes as illustrated in the following schemes. ##STR4##
Suitable examples of the various definitions of the cephem compound (I) of the present invention to be included within the scope of the invention, which are

REFERENCES:
patent: 5162521 (1992-11-01), Farina

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