Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1991-08-21
1994-02-22
Brown, Johnnie R.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
536 72, 536 74, A61K 3170, C07H 1708
Patent
active
052887090
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to new 9-deoxo-9,12-epoxyerythromycin derivatives having antibacterial properties, compositions comprising the new erythromycin derivatives, and methods of treating mammalian patients therewith.
BACKGROUND OF THE INVENTION
Erythromycin and common derivatives are widely used and exhibit desirable activity against a number of gram-positive pathogens. Since some pathogens are less susceptible than others to these drugs, high doses of these antibiotics are occasionally necessary in the treatment of serious or widespread infections. As with all drugs, toxic effects are sometimes observed at higher dosage levels, particularly in patients who are seriously compromised by infection and thus are most in need of treatment. Unfortunately, improvements in potency and spectrum are often accompanied by an increase in toxicity, so that later generation drugs usually represent a compromise between these competing considerations. As a result, there is a continuing search for antibiotics which are more potent against certain organisms, or preferably, against all organisms, than those currently used. Desirably, such drugs will have an improved therapeutic ratio, which is the ratio of the effective therapeutic or prophylactic dose to the toxic dose, usually expressed in terms of the ED.sub.50 /LD.sub.50 ratio.
SUMMARY OF THE INVENTION
This invention relates to 9-deoxo-9,12-epoxyerythromycin A compounds that are useful as broad spectrum antibacterial agents, with activity against gram positive and gram negative bacteria.
The compounds of the invention include those having the following formula I: ##STR1## in which R.sub.1 is an oxo, oxime, hydroxy or amino group at the 11 position; group at the 4" position; and pharmaceutically acceptable salts and esters of the above compounds.
The compositions of the present invention comprise an antibacterially effective amount of a compound of the invention and a pharmaceutically acceptable carrier or diluent.
The method of the present invention includes the treatment of bacterial infections in a mammal in need of such treatment which comprises administering to the mammal an effective amount of a compound of the invention.
DETAILED DESCRIPTION OF THE INVENTION
This invention includes novel 9-deoxo-9,12-epoxyerythromycin A compounds and pharmaceutically acceptable salts and esters thereof. In structural terms, the invention includes compounds of the following formula ##STR2## wherein R.sub.1 is an oxo, oxime, hydroxy, or amino at the 11 position; group at the 4" position; and salts and esters thereof.
Where position R.sub.1 is substituted by a divalent radical, such as oxo, it is understood that a double bond exists between the radical and the carbon at position 11.
This invention also includes antibacterial compositions comprising an antibacterially effective amount of a compound of the invention and a pharmaceutically acceptable carrier or diluent.
This invention further includes a method for treating bacterial infections in a mammal in need of such treatment by administering to the mammal an effective amount of a compound of the invention.
Compounds of this invention offer improved in vitro and in vivo antibiotic potency against certain organisms in comparison to erythromycin. Specific examples of antibiotic potency are disclosed in Tables 2 through 5 hereinbelow.
Compounds that are representative of the preferred class of compounds of this invention include the following compounds as well as their pharmaceutically acceptable salts and esters: rbonyl]amino]erythromycin A; A; amino]-11-oxoerythromycin A; ycin A; 1-oxoerythromycin A; o]erythromycin A; A; xoerythromycin A; A; A; A; and oxoerythromycin.
The preferred intermediates for the preparation of the compounds of Formula I are as follows: )carbonyl]erythromycin A; 9,10-Didehydro-9-deoxo-4",11,12-trideoxy-9,12-epoxy-4"-hydroxyimino-11-oxo erythromycin A; -oxoethyl)erythromycin A; and in A.
The term "oxygen-containing group at the 4" position" as used herein refers to a hydroxy, oxime, al
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Bacino David J.
Edwards Carla M.
Freiberg Leslie A.
Klein Larry L.
Yeung Clinton M.
Abbott Laboratories
Brown Johnnie R.
Danckers Andreas M.
Peselel Elli
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