7'-amino-naphthazarin antibiotic derivatives

Details 7'-amino-naphthazarin antibiotic derivatives 7'-amino-naphthazarin antibiotic derivatives

1994-05-26

1995-12-12

Ivy, C. Warren

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

514379, 514451, 549264, 546193, 548241, A61K 31445, A61K 3135, A61K 3142

Patent

active

054750105

DESCRIPTION:

BRIEF SUMMARY
This application is a 371 of PCT/EP92/02764 filed Nov. 30, 1992.
The present invention concerns novel naphthazarin antibiotic derivatives having general formula I ##STR2## and the pharmaceutically acceptable addition salts thereof, wherein: R represents hydrogen or hydroxy; or tri-substituded phenyl wherein the substituents are independently selected from (C.sub.1 -C.sub.4)alkyl, (C.sub.1 -C.sub.4)alkoxy, hydroxy, amino, halogen, nitro and sulphonyl, or a --NR.sup.2 R.sup.3 group wherein R.sup.2 and R.sup.3 independently represent hydrogen, (C.sub.1 -C.sub.4)alkyl or an amino-protecting group selected from (C.sub.1 -C.sub.5)alkoxycarbonyl, (C.sub.2 -C.sub.4)alkenyloxycarbonyl, cinnamyloxycarbonyl, benzyloxycarbonyl, p-nitrobenzyloxycarbonyl, 3,4-dimethoxy-6-nitrobenzyloxycarbonyl, 2,4-dichloro-benzyloxycarbonyl, 5-benzylisoxazolyl-methoxycarbonyl, 9-anthranylmethoxycarbonyl, diphenylmethoxycarbonyl, isonicotinyloxycarbonyl and S-benzyloxycarbonyl.
These novel naphthazarin antibiotic derivatives are characterized by having an amino or monosubstituted amino group linked to the 7 position of the molecule.
Preferred compounds are those of formula 1 wherein R.sup.3 group wherein R.sup.2 and R.sup.3 independently represent hydrogen, methyl or butyloxycarbonyl.
Most preferred compounds are those wherein R is hydroxy, alk is methylen and X is hydrogen.
In the present description, the terms used above in defining the meanings of R and R.sup.1 are intended to have the meanings commonly assigned to them in the art.
The following list exemplifies in particular some of them: hydrocarbon moiety containing 1, 2, 3 or 4 carbon atoms such as: containing 1, 2, 3 or 4 carbon atoms such as: containing 1, 2, 3 or 4 carbon atoms such as: represent a linear or branched hydrocarbon moiety from 1 to 5 and from 2 to 4 carbon atoms, respectevely, containing a carboxylic function, such as:
Examples of compounds which form part of the present invention are: acceptable salts thereof.
A further object of this invention is to provide a process for preparing these 7'-amino or 7'-substituted amino naphthazarines of formula 1 by starting from the corresponding 7'-methoxy compound.
Purpuromycin and -Rubromycin, which belong to the class of quinonic naphthazarines, are known antimicrobial agents against Gram-positive and Gram-negative bacteria.
Purpuromycin is an antibiotic produced by Actinoplanes ianthinogenes nov. sp. A/1668 which was deposited at the American Type Culture Collection (ATCC) of Rockville, Md. 20852 U.S.A. on Jan. 29, 1973, where it received the accession number ATCC 21884. This strain was accepted under the conditions of the Budapest Treaty as of Jan. 31, 1981. Actinoplanes ianthinogenes nov. sp. A/1668 was described in U.S. Pat. No. 3914257.
Purpuromycin, which is useful in the treatment of infectious vaginitis and for the preparation of topical dosage forms for said treatment (see European Patent Application Publication No. 389924, corresponding to U.S. Ser. No. 07/497,378 now U.S. Pat. No. 5,141,953), corresponds to the compound of the general formula I above wherein R is hydroxy and in position 7' there is a methoxy group instead of the --NH--R.sup.1 group. Its preparation is described in U.S. Pat. No. 3,914,257 wherein its antimicrobial activity is also reported.
According to U.S. Pat. No. 3,914,257 purpuromycin is active in vitro against both Gram-positive and Gram-negative bacteria and fungi, including filamentous fungi (e.g., Trichophyton mentarophytes) and yeasts (e.g., Candida albicans).
Pharmaceutically acceptable water soluble addition salts of purpuromycin are described in U.S. Pat. No. 5,118,705.
.gamma.-Rubromycin is an antibiotic which was isolated from Streptomyces Collinus and S. antibioticus (Brockmann, H. et al. Chem. Ber. 1969, 102, 126; 1970, 103, 1709; Naegeli, H. U. et al, Helv. Chim. Acta, 1980, 63, 1400) and corresponds to the compound of formula I above wherein R is hydrogen and in position 7' there is a methoxy group instead of the --NH--R.sup.1 group.
The above antibiotics can be used as suitabl

Affiliated with

Also associated with

Rating

7'-amino-naphthazarin antibiotic derivatives does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with 7'-amino-naphthazarin antibiotic derivatives, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 7'-amino-naphthazarin antibiotic derivatives will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1360016