Novel semi-synthetic glycopeptides as antibacterial agents

Abstract

Semi-synthetic glycopeptides having antibacterial activity are described, in particular, the semi not synthetic glycopeptides described herein are made by chemical modification of a glycopeptide (Compound A, Compound B, Compound H or Compound C) or monosaccharide made by hydrolyzing the disaccharide moiety of the amino acid-4 of the parent glycopeptide in acidic medium to give the amino acid-4 monosaccharide; conversion of the monosaccharide to the amino-sugar derivative; acylation of the amino substituent on the amino acid-4 amino-substituted sugar moiety on these scaffolds with certain acyl groups; and conversion of the acid moiety on the macrocyclic ring of these scaffolds to certain substituted amides. Key reaction is the treatment of properly protected intermediate compound with isocyanate. Also provided are methods for the synthesis of the compounds, pharmaceutical compositions containing the compounds, and methods of use of the compounds for the treatment and / or prophylaxis of diseases, especially bacterial infections.

Description

[0001] cross reference [0002] This application claims priority to U.S. Provisional Patent Application No. 61 / 220,167, filed June 24, 2009, and PCT Patent Application No. PCT / US2008 / 085716, filed December 5, 2008, the contents of which are adopted by This reference is incorporated herein in its entirety. technical field [0003] The present invention describes semi-synthetic glycopeptides having antibacterial activity, pharmaceutical compositions comprising these compounds, and methods of treatment using the semi-synthetic glycopeptides. Background technique [0004] The emergence of drug-resistant bacterial strains has highlighted the need for the synthesis and identification of antibiotics with improved activity. Naturally occurring and semi-synthetic glycopeptide antibiotics used against bacterial infections include, for example, vancomycin with structures A, B, C, D, E, F, G, and H, desmethylvancomycin, erythromycin Compounds such as trichoplanin, teicoplanin (a compo...

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Problems solved by technology

[0007] These compounds are used to treat and prevent bacterial infections, but like other antimicrobial agents, strains of bacteria that are resistant or insufficiently sensitive to these compounds have been identified and have been found to have limited effect on certain bacterial infections , for example, for pulmonary S. aureus infections caused by Compound A moderately resistant S. aureus, or for infections caused by Compound A-resistant Enterococci

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