US 2022/0177508 A1 · C10-Cyclic Substituted 13-Membered Macrolides and Uses Thereof

C10-Cyclic Substituted 13-Membered Macrolides and Uses Thereof

AssigneesZikani Therapeutics , Inc., President and Fellows of Harvard College

InventorsRoger B. Clark, Richard Alm, Wesley Francis Austin, Vijaya Gondi, Philip Hogan, Ivan Jewett, Sushmita D. Lahiri, Jonathan F. Lawrence, Xiben Li, Shuhao Shi, Wenying Wang, Yoshitaka Ichikawa, Andrew G. Myers, Ziyang Zhang, Peter Niels Carlsen, Md. Ataur Rahman

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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.

Claims29

Dependent claims

1-120. (canceled)

A compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:
one of R2a and R2b is selected from the group consisting of H, halo, optionally substituted C1-10 alkyl, optionally substituted C1-10 alkoxy, and optionally substituted C1-10 alkenyl, wherein C1-10 alkyl, C1-10 alkoxy, and C1-10 alkenyl are optionally substituted with one or more groups selected from the group consisting of halo, aryl, amino, alkyl, heteroalkyl, heteroalkenyl, heterocycloalkyl, and heteroaryl;
and the other of R2a and R2b is selected from the group consisting of halo, optionally substituted C1-10 alkyl, optionally substituted C1-10 alkoxy, and optionally substituted C1-10 alkenyl, wherein C1-10 alkyl, C1-10 alkoxy, and C1-10 alkenyl are optionally substituted with one or more groups selected from the group consisting of halo, aryl, amino, alkyl, heteroalkyl, heteroalkenyl, heterocycloalkyl, and heteroaryl;
each of R4a and R4b is independently selected from the group consisting of —H, and optionally substituted C1-10 alkyl;
R5 is selected from the group consisting of —H, an oxygen protecting group, and
wherein “” indicates a point of attachment
R6a is optionally substituted C1-10 alkyl;
R6b is —H, optionally substituted C1-10 alkyl, optionally substituted C1-10 hydroxyalkyl, and optionally substituted allyl;
R8a and R8b are each independently selected from the group consisting of —H and optionally substituted C1-10 alkyl;
R9a is selected from the group consisting of —H, —CO2-alkylene-aryl, —C(═O)-alkyl, and optionally substituted C1-10 alkyl;
one of R10a and R10b is selected from the group consisting of —H, optionally substituted C1-10 alkyl, —CO2H, and —CO2-alkyl;
and
the other of R10a and R10b is selected from the group consisting of optionally substituted saturated or partially unsaturated cycloalkyl containing at least one double bond, optionally substituted saturated or partially unsaturated heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
and
R11a and R11b are each independently selected from the group consisting of —H and optionally substituted C1-10 alkyl.

12 more elements

Dependencies are inferred from the claim text.