Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1997-03-12
1999-11-23
Berch, Mark L
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
540302, C07D51906, A61K 31425, A61K 31495
Patent
active
059901012
DESCRIPTION:
BRIEF SUMMARY
This application is a U.S. National Phase Application under 35 USC 371, of International Application No. PCT/JP96/00573 filed Mar. 8, 1996.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to carbapenem derivatives having potent antibacterial activity against a wide spectrum of bacteria. More particularly, the present invention relates to novel carbapenem derivatives having a substituted or unsubstituted imidazo[5,1-b]thiazolium-6-ylmethyl group at the 2-position of the carbapenem ring.
2. Background Art
Carbapenem derivatives, by virtue of potent antibacterial activity against a wide spectrum of bacteria, have been energetically studied as a highly useful .beta.-lactam agent, and Imipenem, Panipenem, and Meropenem have been clinically used.
Both Imipenem and Panipenem, however, are used as a mixture due to instability against renal dehydropeptidase-1 ("DHP-1") in the case of Impenem and in order to reduce nephrotoxicity in the case of Panipenem.
In recent years, research and development of carbapenem derivatives having a methyl group at the 1.beta.-position have been made for use of these compounds as a single active ingredient in preparations because they are highly stable against DHP-1. However, many of the compounds including Meropenem, which has been recently put on the market, have a pyrrolidine skeleton at the 2-position in its chemical structure. Further, they are not always satisfactory in antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP), and resistant Pseudomonas aeruginosa which have posed a serious clinical problem these days. Thus, a need still exists for novel carbapenem antibiotics which have improved antibacterial activity against these bacteria.
N-Onium-salt-type carbapenem derivatives having methylene at the 2-position of the carbapenem are disclosed in Japanese Patent Laid-Open No. 151191/1986. This publication, however, neither specifically describes any bicyclic heterocyclic ring in a 5+5 form nor refers to any imidazo[5,1-b]thiazole proposed in the present invention.
The present inventors have previously found that novel cephem derivatives having heterocyclic imidazo[5,1-b]thiazole at the 3-position of the cephem ring have excellent antibacterial activity against a wide spectrum of bacteria (Japanese Patent Application Nos. 230573/1993 and 211908/1994).
SUMMARY OF THE INVENTION
The present inventors have now succeeded in synthesizing novel carbapenem derivatives having a substituted or unsubstituted imidazo[5,1-b]thiazolium-6-ylmethyl group at the 2-position and found that these derivatives have potent antibacterial activity against a wide spectrum of bacteria from Gram-positive bacteria to Gram-negative bacteria including Pseudomonas aeruginosa and, in addition, have potent antibacterial activity against .beta.-lactamase-producing bacteria and MRSA.
Thus, an object of the present invention is to provide novel carbapenem derivatives having potent antibacterial activity against a wide spectrum of bacteria.
Another object of the present invention is to provide pharmaceutical compositions comprising the carbapenem derivative of the present invention.
A further object of the present invention is to provide a method for treating infectious diseases, comprising the step of administering the carbapenem derivative of the present invention.
The compounds according to the present invention are carbapenem derivatives represented by the following formula (I): ##STR2## wherein R.sup.1 represents a hydrogen atom or lower alkyl; and represent be substituted by lower alkyl, hydroxy lower alkyl, lower alkyloxycarbonyl, or aminosulfonyloxy lower alkyl; cycloalkyl, C.sub.2-4 alkenyl, and C.sub.2-4 alkynyl may be substituted by a group selected from the group consisting of a halogen atom; hydroxyl; nitro; cyano; carboxyl; formyl; lower alkyloxy; lower alkylthio; lower alkyloxycarbonyl; carbamoyl; N-lower alkylcarbamoyl; hydroxyaminocarbonyl; lower alkylcarbonyl; lower alkylcarbo
REFERENCES:
patent: 4680292 (1987-07-01), Christensen et al.
Aihara Kazuhiro
Atsumi Kunio
Ishii Miyuki
Iwamatsu Katsuyoshi
Kano Yuko
Berch Mark L
Meiji Seika Kabushiki Kaisha
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