Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1985-12-17
1987-05-26
Daus, Donald G.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
540220, C07D50146
Patent
active
046687823
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a cephalosporin derivative. More particularly, this invention relates to a crystalline anhydride or a specific hydrate of cephalosporin derivative which has the outstanding stability.
BACKGROUND OF THE ART
The cephalosporin derivatives which have a 2-(2-aminothiazole-4-yl)-2-methoxyiminoacetoamido group at the 7-position are known as the antibiotics having a strong antibacterial activity.
For instance, (6R,7R)-7-[(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetoamido]-3-(1-qui nuclidiniummethyl)-3-cephem-4-carboxylate which is expressed by the following formula ##STR1## has a betaine structure and this compound is a cephalosporin derivative which has a strong antibacterial activity against Gram-positive and Gram-negative bacterials (Japanese Laid-Open Patent Publication No. 219292/1984), corresponding to U.S. Pat. No. 4,525,473.
Generally speaking, however, these cephalosporin derivatives are chemically unstable since the .beta.-lactam ring in their molecules is liable to be hydrolyzed.
It is, therefore, essentially important to have such cephalosporin derivatives prepared in a stable form when they are to be used as pharmaceuticals.
DISCLOSURE OF THE INVENTION
One of the objects of this invention is to provide a stabilized crystalline (6R,7R)-7-[(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetoamido]-3-(1-qui nuclidiniummethyl)-3-cephem-4-carboxylate or its derivative.
Another object of this invention is to provide a process for the production of a crystalline (6R,7R)-7-[(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetoamido]-3-(1-qui nuclidiniummethyl)-3-cephem-4-carboxylate or its derivative.
A further object of this invention is to provide a novel cephalosporin derivative (6R,7R)-7-[(Z)-2-(5-amino-1-thia-2,4-diazole-3-yl)-methoxyiminoacetoamido] -3-(1-quinuclidiniummethyl)-3-cephem-4-carboxylate.
Other objects of this invention will become apparent from the following description.
These objects and advantages are achieved by a crystalline anhydride, hemihydrate, monohydrate, or trihydrate of a cephalosporin derivative (6R,7R)-7-[(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetoamide]-3-(1-qui nuclidiniummethyl)-3-cephem-carboxylate or (6R,7R)-7-[(Z)-2-(5-amino-1-thia-2,4-diazole-3-yl)-2-methoxyiminoacetoamid o]-3-(1-quinuclidiniummethyl)-3-cephem-4-carboxylate.
BEST MODE OF CARRYING OUT THE INVENTION
A cephalosporin derivative which is the subject of the present invention is (6R,7R)-7-[(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetoamido]-3-(1-qui nuclidiniummethyl)-3-cephem-4-carboxylate (hereinafter referred to as a cephalosporin derivative A) expressed by the following formula ##STR2## or its derivative, (6R,7R)-7-[(Z)-2-(5-amino-1-thia-2,4-diazole-3-yl)-2-methoxyiminoacetoamid o]-3-(1-quinuclidiniummethyl)-3-cephem-4-carboxylate (hereinafter referred to as a cephalosporin derivative B) expressed by the following formula. ##STR3##
The cephalosporin derivative A or B has a betaine structure in its molecules and a crystalline anhydride, hemihydrate, monohydrate, or trihydrate of such a cephalosporin derivative which has a betaine structure excels others in stability and is suitable for medical use.
A crystalline anhydride, hemihydrate, monohydrate, or trihydrate of cephalosporin A or B can be obtained by dissolving a cephalosporin derivative A or B, which is prepared in an amorphous state, in an aqueous organic solvent, then adding thus obtained solution to an organic solvent or cooling the solution, and further drying the solution, if necessary.
What is referred to as an aqueous organic solvent in the above is a mixture of water and a solvent mixable with water. As the solvent mixable with water, such alcohols as methanol, ethanol, and isopropanol; such ketones as acetone, methyl ethyl ketone, and methyl isobutyl ketone; and such ethers as dioxane and tetrahydrofuran, for instance, are used. They may be used singly or as a mixed solvent. Of the solvents exemplified in the above, alcohols and ketones are preferable. The mixing ratio between said s
REFERENCES:
patent: 3502663 (1970-03-01), Barnes
patent: 3862186 (1975-01-01), Silvestri
patent: 4525473 (1985-06-01), Aburaki et al.
Harada Toshiaki
Ichikawa Yataro
Imai Hiroshi
Suzuki Yoji
Yoshisato Eishin
Cassatt Barbara
Daus Donald G.
Teijin Limited
LandOfFree
Anhydrous crystalline or crystalline hemihydrate monohydrate or does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Anhydrous crystalline or crystalline hemihydrate monohydrate or , we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Anhydrous crystalline or crystalline hemihydrate monohydrate or will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-704775