Erythromycin derivatives

Details Erythromycin derivatives Erythromycin derivatives

1999-07-20

2000-12-19

Peselev, Elli

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Carbohydrate doai

536 72, 536 75, A61K 3170, C07H 1708

Patent

active

061627941

DESCRIPTION:

BRIEF SUMMARY
BACKGROUND OF THE INVENTION

This invention relates to novel 11-amino-9-deoxo-11-deoxy-9-imino-5-O-desosaminyl-6-O-methyl-3-oxoerythron olide A, 9N,11N-dihydropyrazole, 11,12-carbamate and 9,11-diamino-9-deoxo-11-deoxy-5-O-desosaminyl-6-O-methyl-3-oxoerythronolid e A, 9N,11N-tetrahydropyrazole, 11,12-carbamate derivatives. The compounds of this invention are useful as antibiotic agents in mammals, including man, as well as in fish and birds. The compounds of the present invention are broad-spectrum macrolide antibiotics that are effective against infections caused by certain gram-positive and gram-negative bacteria as well as protozoa.
Macrolide antibiotics are known to be useful in the treatment of a broad spectrum of bacterial infections and protozoa infections in mammals, fish and birds. Such antibiotics include various derivatives of erythromycin A such as azithromycin which is commercially available and is referred to in U.S. Pat. Nos. 4,474,768 and 4,517,359, both of which are incorporated herein by reference in their entirety. Additional macrolides are referred to in U.S. patent application Ser. No. 60/063676, filed Oct. 29, 1997 (Yong-Jin Wu), U.S. application Ser. No. 60/063161, filed Oct. 29, 1997 (Yong-Jin Wu), U.S. application Ser. No. 60/054866, filed Aug. 6, 1997 (Hiroko Masamune, Yong-Jin Wu, Takushi Kaneko and Paul R. McGuirk), all of which are incorporated herein by reference in their entirety. Like azithromycin and other macrolide antibiotics, the novel macrolide compounds of the present invention possess potent activity against various bacterial infections and protozoa infections as described below.


SUMMARY OF THE INVENTION

The present invention relates to compounds of the formula: ##STR2## and to pharmaceutically acceptable salts thereof, wherein: R is H, R.sup.1, C(.dbd.O) R.sup.1, C(.dbd.O) OR.sup.1, (CH.sub.2).sub.m R.sup.3, or is absent, wherein m is an integer from 0 to 6; said heterocycyl and aryl groups are optionally substituted by 1 to 3 substituents independently selected from the group consisting of --C(O)OR.sup.4, --OR.sup.4, C.sub.1 -C.sub.6 alkanoyl, halo, nitro, cyano, C.sub.1 -C.sub.6 alkyl, --NR.sup.4 R.sup.5, --S(C.sub.1 -C.sub.6 alkyl), --SO(C.sub.1 -C.sub.6 alkyl), --SO.sub.2 (C.sub.1 -C.sub.6 alkyl) and --SO.sub.2 NR.sup.4 R.sup.5, -C.sub.10 alkyl, saturated or unsaturated, wherein one or two carbons of said alkyl are optionally replaced by a heteroatom selected from O, S and N, wherein one or two carbons of said alkyl are optionally replaced by a heteroatom selected from O, S and N, and are optionally substituted by 1 to 3 substituents selected from the group consisting of --C(O)OR.sup.4, --OR.sup.4, C.sub.1 -C.sub.6 alkanoyl, halo, nitro, cyano, C.sub.1 -C.sub.6 alkyl, 5-10 membered heterocycyl, C.sub.6 -C.sub.10 aryl, --NR.sup.4 R.sup.5, --S(C.sub.1 -C.sub.6 alkyl), --SO(C.sub.1 -C.sub.6 alkyl), --SO.sub.2 (C.sub.1 -C.sub.6 alkyl) and --SO.sub.2 NR.sup.4 R.sup.5 ; and above.
The dashed line connected to C-9 represents an optional bond that may optionally exist when R is absent.
More specific embodiments of this invention include compounds of formula I wherein R is H.
More specific embodiments of this invention include compounds of formula I wherein Z is H.
Other more specific embodiments of this invention include compounds of formula I wherein R.sup.1 is absent and the dashed line connected to C-9 represents an additional bond.
Other more specific embodiments of this invention include compounds of formula I wherein R is (CH.sub.2).sub.m R.sup.3, where m is an integer ranging from 0 to 6 and R.sup.3 is 5-10 membered heterocyclyl or C.sub.6 -C.sub.10 aryl. Specific embodiments of R.sup.3 include quinolin-4-yl, 4-phenyl-imidazol-1-yl, imidazo(4,5-b)pyridin-3-yl, 4-pyridin-3-yl-imidazol-1-yl and pyridin-3-yl.
Examples of preferred compounds of this invention include: lide A, 9N,11N-dihydropyrazole, 11,12-carbamate; A, 9N, 11N-tetradropyrazole, 11,12-carbamate; olin-4-yl)-propyl)erythronolide A, 9N,11N-tetrahydropyrazole, 11,12-carbamate; pyl)erythronolide A, 9N,11

REFERENCES:
patent: 5631355 (1997-05-01), Asaka et al.

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