5-O-desosaminylerythronolide derivatives

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

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536 72, 536 74, C07H 1708

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active

055233996

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

The present invention relates to novel derivatives of an antibiotic erythromycin. More particularly, it relates to novel derivatives of 5-O-desosaminylerythronolide derivatives and pharmaceutically acceptable acid addition salts thereof.


BACKGROUND ART

Erythromycin is an antibiotic clinically widely used as an agent for curing infectious diseases caused by Gram-positive bacteria, some Gram-negative bacteria, mycoplasmas, etc. Many derivatives of erythromycin have been produced for improving the biological and/or pharmacodynamic characteristics of erythromycin. As 5-O-desosaminylerythronolide derivatives, 3-O-acyl-5-O-desosaminylerythronolide derivatives, for example, have been disclosed in U.S. Pat. No. 3,923,784. 5-O-desosaminylerythronolide derivatives, however, have been generally considered to be poor in antibacterial activity, and the antibacterial activity of the above-exemplified derivatives is also very weak. An object of the present invention is to provide novel antibiotics having a strong antibacterial activity.


DISCLOSURE OF THE INVENTION

The present inventors conducted various researches on the antibacterial activity of 5-O-desosaminylerythronolide derivatives and consequently found that compounds obtained by introducing a carbamoyl group into 5-O-desosaminylerythronolide derivatives at the 3-position have an unexpectedly strong antibacterial activity, whereby the present invention has been accomplished.
The present invention is 5-O-desosaminylerythronolide derivatives represented by the formula: ##STR2## [wherein each of R.sup.1 and R.sup.2 is a hydrogen atom; a phenyl group; a substituted phenyl group having 1 to 5 substituents selected from halogen atoms, nitro groups and amino groups; a C.sub.1 -C.sub.15 alkyl group; a C.sub.2 -C.sub.15 alkyl group containing at least one nitrogen atom, oxygen atom or sulfur atom; a C.sub.7 -C.sub.15 aralkyl group; or a C.sub.7 -C.sub.15 aralkyl group containing at least one nitrogen atom, oxygen atom or sulfur atom; R.sup.1 and R.sup.2 being able to be groups which form a ring together with the adjacent nitrogen atom, Z is an oxygen atom or a group represented by the formula .dbd.N--O--R.sup.3 (wherein R.sup.3 is a hydrogen atom; a C.sub.1 -C.sub.8 alkyl group; a C.sub.2 -C.sub.18 alkyl group containing at least one nitrogen atom, oxygen atom or sulfur atom; a benzyl group; or a substituted benzyl group having 1 to 5 substituents selected from halogen atoms and C.sub.1 -C.sub.4 alkyl groups), V is a hydroxyl group and W is a hydrogen atom or a hydroxyl group, or V and W represent together with the carbon atoms at the 11- and 12-positions a group represented by the formula: ##STR3## or a group represented by the formula: ##STR4## R is a hydrogen atom, a C.sub.2 -C.sub.15 alkoxycarbonyl group, a C.sub.2 -C.sub.15 alkoxycarbonyl group containing at least one oxygen atom in its alkyl moiety, a C.sub.2 -C.sub.15 acyl group, a C.sub.2 -C.sub.15 acyl group containing at least one oxygen atom, or a pyridylcarbonyl group] and pharmaceutically acceptable acid addition salts thereof.
In the present invention, the halogen atoms are fluorine, chlorine, bromine and iodine atoms. The term "alkyl group" means a linear one or a branched one. As the C.sub.2 -C.sub.15 alkyl group containing at least one nitrogen atom, oxygen atom or sulfur atom, there can be exemplified aminoethyl group, dimethylaminoethyl group, benzylaminoethyl group, N-benzyl-N-methylaminoethyl group, dibenzylaminoethyl group, 2,3-dihydroxypropyl group, 3-aminopropyl group and 2-hydroxy-3-aminopropyl group. As the C.sub.7 -C.sub.15 aralkyl group, there can be exemplified benzyl group, phenethyl group and diphenylmethyl group. As the C.sub.7 -C.sub.15 aralkyl group containing at least one nitrogen atom, oxygen atom or sulfur atom, there can be exemplified nitrobenzyl group, methoxybenzyl group, methylthiobenzyl group, aminobenzyl group and dimethylaminobenzyl group. The term "C.sub.2 -C.sub.15 alkoxycarbonyl group" means a substituted carbonyl group having an alkoxy group as the subs

REFERENCES:
patent: 3923784 (1975-12-01), Kierstead et al.

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