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|Title:||Glycopeptide antibiotic derivatives|
|Abstract:||The present invention provides glycopeptide antibiotic derivative compounds. These derivative compounds possess antibacterial activity against a wide variety of bacteria, including activity against vancomycin-resistant isolates. Methods of making and using these glycopeptide antibiotic derivative compounds are also provided.|
|Inventor(s):||Cooper; Robin D. G. (Indianapolis, IN), Huff; Bret E. (Mooresville, IN), Nicas; Thalia I. (Indianapolis, IN), Quatroche; John T. (Indianapolis, IN), Rodriguez; Michael J. (Indianapolis, IN), Snyder; Nancy J. (Charlottesville, IN), Staszak; Michael A. (Indianapolis, IN), Thompson; Richard C. (Frankfort, IN), Wilkie; Stephen C. (Indianapolis, IN), Zweifel; Mark J. (Indianapolis, IN)|
|Assignee:||Eli Lilly and Company (Indianapolis, IN)|
1. A compound of the formula: ##STR9## or a salt thereof.
2. A pharmaceutical composition comprising 4 [4 chlorophenyl]benzyl-A82846B, wherein the 4-[4-chlorophenyl]benzyl is on the amino group of the 4 epi-vancosaminyl sugar of the 4-epi-vancosaminyl-O-glycosyl disaccharide or a salt thereof.
3. A method of treating a susceptible bacterial infection in an animal which comprises administering to the animal an antibacterially effective amount of a compound of claim 1 or a composition of claim 2.
4. A method of claim 3 wherein the bacterial infection comprises vancomycin-resistant enteroccoci.
5. A process for the preparation of a compound of claim 1 which comprises
a) reacting A82846B with 4'-chlorobiphenylcarboxaldehyde in a polar solvent;
b) continuing the reaction until formation of a Schriff's base; and
c) reducing the Schiff's base by addition of a reducing agent.
6. A process for the preparation of a compound of claim 1 which comprises reacting A82846B with 4'-chlorobiphenylcarboxaldehyde in a polar solvent and in the presence of a reducing agent, for a time sufficient to produce a compound of claim 1.
7. A process of claim 6 wherein the reducing agent is sodium cyanoborohydride.
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