Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1994-05-16
1997-06-03
Ford, John M.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
540225, C07D50124, A61K 31545
Patent
active
056355009
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/JP93/01326 filed Sep. 16, 1993.
TECHNICAL FIELD
This invention relates to a novel cephem compound, a process for producing the compound and a pharmaceutical composition comprising the same.
PRIOR ART
With the spreading use of third-generation cephalosporins in recent years, infectious diseases associated with meticillin-resistant Staphylococcus aureus (MRSA) are presenting serious problems. These cephalosporins of the third generation have potent activity against gram-negative bacilli but because of their relatively low activity against gram-positive cocci, the strains of S. aureaus which are resistant to .beta.-lactam antibiotics have increased in number and the resultant refractory infections constitute a serious threat today. The only therapeutic drug available for MRSA infections today is vancomycin which is a polypeptide antibiotic but since it has side effects such as eczema and renal toxicity, vancomycin calls for caution in administration.
As 3-thiovinylcephalosporin derivatives having antimicrobial activity, the compounds described in Japanese Examined Patent Application 17592/1987 and Japanese Patent Unexamined Application 130292/1984 (EP-A111281) gazettes are known to this day. The latter gazette describes compounds having an alkoxyimino group in the side chain in the 7-position and a thiovinyl quaternary ammonium salt in the. 3-position of the cephalosporin nucleus but does not refer to a hydroxyimino group. Furthermore, there is no disclosure in these prior art publications that a 3-thiovinylcephalosporin derivative is active against MRSA.
Disclosure of Invention
It is an object of this invention to provide cephem compounds having excellent antimicrobial activity and, in particular, novel cephem compounds which are active against MRSA and safe to use.
It is another object of the invention to provide a process for producing the above-mentioned compounds.
A further object of this invention is to provide a pharmaceutical composition for the therapy of MRSA-induced infectious diseases.
For the purpose of accomplishing the above-mentioned objects, the inventors of this invention synthesized and screened a variety of cephem compounds and discovered that a cephem compound having a thiovinyl quaternary ammonium salt in the 3-position and a hydroxyimino group in the side chain moiety in the 7-position of the cephalosporin nucleus has excellent antimicrobial activity and is particularly active against MRSA. This invention has been developed on the basis of the above discovery.
The cephem compound of this invention is a novel compound of the following general formula (1) ##STR4## [wherein Q represents CH or N, R.sup.1 represents a carboxylate or a carboxyl group, and R represents the group ##STR5## or the group ##STR6## where R.sup.2 represents a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a hydroxy(lower)alkyl group or the group --A--CO--R.sup.3 (where A represents a C.sub.1-6 alkylene group, a phenylene group, a benzylene group or a xylylene group, R.sup.3 represents a hydroxyl group, a lower alkyl group, a phenyl group which may be substituted by hydroxyl, an amino group, a lower alkylamino group or an amino acid amino group), n represents an integer of 0 or 1 through 3, B.sup.- represents an anion, f is equal to 0 when .sup.- R.sup.1 represents a carboxylate and 1 when R.sup.1 represents a carboxyl group, and the ring C represents a 5-membered heterocyclic group of not more than 4 nitrogen atoms, which may be substituted by lower alkyl].
The respective groups mentioned in this specification specifically mean the following.
The lower alkyl group includes C.sub.1-6 alkyl groups, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl and hexyl, among others.
The lower alkenyl group includes C.sub.2-6 alkenyl groups, such as vinyl, allyl, crotyl, 2-pentenyl and 2-hexenyl, among others.
The lower alkynyl group includes C.sub.2-6 alkynyl groups, such as ethynyl, 1-propynyl, 2-propynyl, 2-butynyl, 1-methyl-2-propynyl, 2-pe
REFERENCES:
patent: 4307116 (1981-12-01), Farge et al.
patent: 4584290 (1986-04-01), Takaya et al.
Akagi Hiroshi
Hanaki Hideaki
Hara Yoshifumi
Hyodo Akio
Yasui Masaru
Ford John M.
Otsuka Kagaku Kabushiki Kaisha
Taiho Pharmaceutical Co. Ltd.
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