Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1993-04-21
1996-06-18
Peselev, Elli
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
514 36, 514 40, 536 136, 536 137, 536 138, A61K 3170, C07H 1522
Patent
active
055277810
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to new semi-synthetic aminoglycosidic antibiotics, namely such 5-deoxy-5,5-difluorostreptamine derivatives which are derived from aminoglycosidic antibiotics or their deoxy derivatives, as well as 1-N-acylated derivatives of said 5-deoxy-5,5-difluorostreptamine derivatives. This invention also relates to antibacterial compositions containing these new compounds. Further, this invention relates to processes for the production of these new compounds. These new compounds of this invention are useful as antibacterial agent for therapeutic treatment of bacterial infections, since they exhibit high antibacterial activities against such bacteria sensitive to aminoglycosidic antibiotics, and also against such bacteria resistant to aminoglycosidic antibiotics and have a characteristically and remarkably reduced toxicity.
BACKGROUND ART
Various deoxy derivatives of kanamycin A, B or C have useful antibacterial activities, but the antibacterial spectra of these known deoxy-derivatives of kanamycins are of different ranges. Accordingly, it is always demanded that new, antibacterial compounds having any more excellent properties than the known kanamycin derivatives should be produced and provided.
The present inventors have synthetized 3'-deoxy-3'-fluorokanamycin A (see Japanese patent application first publication "Kokai" No. 40297/86 and U.S. Pat. No. 4,634,688). Further, the present inventors have synthetized 3'-deoxy-3'-fluorokanamycin B and found that 3'-deoxy-3'-fluorokanamycin B has remarkable antibacterial activities against various gram-positive and gram-negative bacteria, including the resistant bacteria (see Japanese patent application first publication "Kokai" No. 140597/86). And, the present inventors have synthetized 3',4'-dideoxy-3'-fluorokanamycin B (see Japanese patent application first publication "Kokai" No. 51694/87 and U.S. Pat. No. 4,845,082 specification).
Furthermore, the present inventors have synthetized 1-N-[(RS)- or (S)-3-amino-2-hydroxy-propionyl]- or 1-N-[(S)-4-amino-2-hydroxybutyryl]-3'-deoxy-3'-fluorokanamycin A or B (see Japanese patent application first publication "Koaki" No. 236791/86).
Moreover, the present inventors have synthetized 2', 3'-dideoxy-2'-fluorokanamycin A (see the specification of Japanese patent application first publication "Kokai" No. 143393/86) as well as 1-N-[(RS)- or (S)-3-amino-2-hydroxypropionyl]- or 1-N-[(S)-4-amino-2-hydroxybutyryl]-2',3'-dideoxy-2'-fluorokanamycin A (see Japanese patent application first publication "Koaki" No. 93296/87 and U.S. Pat. No. 4,661,474specification).
On the other hand, a literature "Aminocyclitol Antibiotics" pages 371-392, edited by K. L. Rinehart and T. Suami (published from American Chemical Society in 1980) discloses the production of 5-deoxy-5-fluoro-5-epi-sisomicin according to a method comprising reacting diethylaminosulfur trifluoride (hereinafter abbreviated as DAST) with such a protected derivative of sisomicin whose all the amino groups and all the hydroxyl groups except the 5-hydroxyl group have been protected. Further, a literature "Journal of Carbohydrate Chemistry" Vol. 1, page 289 (1982) discloses the production of 4"-deoxy-4"-fluoro-4"-epi-kanamycin A with starting from kanamycin A, although this literature shows that the antibacterial activity of this 4"-deoxy-4"-fluoro-4"-epi-kanamycin A is lower than that of kanamycin A.
Furthermore, a literature "Tetrahedron Letters" Vol. 24, No. 17, pages 1763-1766(1983) discloses that 6"-deoxy-6"-fluorokanamycin A is produced, that 5,6"-dideoxy-5,6"-difluoro-5-epi-kanamycin A is produced and further that 5-deoxy-5-fluoro-5,4"-di-epi-kanamycin A is produced.
In this literature "Tetrahedron Letters" Vol. 24, No. 17, pages 1763-1766(1983), there is disclosed that 6"-deoxy-6"-fluorokanamycin A, 5,6"-dideoxy-5,6"-difluoro-5-epi-kanamycin A and 5-deoxy-5-fluoro-5,4"-di-epi-kanamycin A show antibacterial activities substantially as high as that of kanamycin A. Accordingly, this literature does not give any teaching that the antibacterial
REFERENCES:
patent: 4284764 (1981-08-01), Daniels et al.
patent: 4547492 (1985-10-01), Umezawa et al.
patent: 4873225 (1989-10-01), Umezawa et al.
Fukatsu Shunzo
Shitara Tetsuo
Takeuchi Tomio
Tsuchiya Tsutomu
Umemura Eijiro
Peselev Elli
Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai
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