C10-alkylene substituted 13-membered macrolides and uses thereof

Abstract

Provided are 13-membered macrolides for the treatment of infectious diseases. The 13-membered macrolides described herein are azaketolides. Also provided are methods for preparing the 13-membered macrolides, pharmaceutical compositions comprising the 13-membered macrolides, and methods of treating infectious diseases, and in particular, disease resulting from Gram negative bacteria using the disclosed macrolides. Formula (I).

Description

[0001] Cross References to Related Applications [0002] This application claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Application 62 / 769,383, filed November 19, 2018. The disclosure of this prior application is considered part of the disclosure of the present application and is hereby incorporated by reference in its entirety. Background technique [0003] Emerging resistance to existing antibiotics is rapidly developing as a worldwide crisis, especially for infections originating from resistant Gram-negative bacteria. Pathogenic bacteria can transmit genes encoding antibiotic resistance both vertically (to their descendants) and horizontally (to neighboring bacteria of different lineages), and thus antibiotic resistance can develop rapidly (especially in the nosocomial (hospital) environment). See, eg, Wright, Chem. Commun. (2011) 47:4055-4061. Health care-associated infections kill more than 99,000 people in the United States each year, more than all casua...

AI Technical Summary

Problems solved by technology

Despite greatly improved ribosome binding, ketolides such as telithromycin and solithromycin have not addressed several of the more recent forms of macrolide resistance developing in the in-hospital setting, especially ribosomal methylation and RNA point mutations

[0006] Therefore, the discovery and development of new antibiotics effective against drug-resistant bacteria, especially Gram-negative bacteria, represents a current unmet medical need

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