Lincosamide antibiotics and uses thereof

Patent metadata

Field	Value
Publication number	US-11767341-B2
Application number	US-202117469353-A
Country	US
Kind code	B2
Filing date	Sep 8, 2021
Priority date	Aug 10, 2017
Publication date	Sep 26, 2023
Grant date	Sep 26, 2023

Abstract

Provided are lincosamide compounds for the treatment of infectious diseases. The lincosamides described herein are modified at the amino acid (southern) region. The lincosamides may have further modification at the C-1 and C-7 positions of the aminooctose (northern) region, thus distinguishing them from lincomycin and clindamycin. Also provided are methods for preparing the lincosamide compounds, pharmaceutical compositions comprising the lincosamide compounds, and methods of treating infectious diseases using the disclosed lincosamide compounds.

First claim

What is claimed is:

1. A compound of Formula (I-h):

or a pharmaceutically acceptable salt thereof, wherein:
A is substituted or unsubstituted alkyl;
R 1 is —OR A , —N(R A ) 2 , or —SR A ;
R 7 is hydrogen or unsubstituted alkyl;
R 8 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heteroaliphatic, —C(═NR A )R A , —C(═NR A )OR A , —C(═NR A )N(R A ) 2 , —C(═O)R A , —C(═O)OR A , —C(═O)N(R A ) 2 , —S(O) 2 R A , or a nitrogen protecting group;
R 9 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aralkyl, or substituted or unsubstituted heteroaliphatic; and
each occurrence of R A is, independently, hydrogen, substituted or unsubstituted acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroaliphatic, substituted or unsubstituted carbocyclyl, substituted or unsubstituted carbocyclylalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted hetaralkyl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom, or two R A groups are joined to form a substituted or unsubstituted heterocyclyl ring, or a substituted or unsubstituted heteroaryl ring.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
A is of the formula:

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
R 1 is —SR A .

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
R 1 is —SCH 3.

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
R 7 is hydrogen.

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
R 8 is hydrogen.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
R 9 is substituted or unsubstituted alkyl.

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
R 9 is unsubstituted alkyl.

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
R 9 is unsubstituted C 1-4 alkyl.

10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
A is of the formula:

R 1 is —SCH 3 ;
R 7 is hydrogen;
R 8 is hydrogen; and
R 9 is unsubstituted C 1-4 alkyl.

11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is:

FSA-510011

FSA-510021

FSA-510022

FSA-510065

FSA-510072

FSA-510073

FSA-510074

FSA-512011

FSA-512012

12. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

13. A method of treating an infectious disease comprising administering an effective amount of a compound of claim 1 , or pharmaceutically acceptable salt thereof, to a subject in need thereof.

14. The method of claim 13 , wherein the infectious disease is a bacterial infection.

15. The method of claim 14 , wherein the bacterial infection is a Staphylococcus infection, a Streptococcus infection, an Enterococcus infection, an Acetinobacter infection, a Clostridium infection, a Bacterioides infection, an Escherichia infection, a Pseudomonas infection, a Klebsiella infection, a Haemophilus infection, a C. difficile infection, or a B. fragilis infection.

16. A method of treating an infectious disease, wherein the infectious disease is a fungal, bacterial, viral, or parasitic infection, the method comprising administering an effective amount of a compound of Formula (I), or pharmaceutically acceptable salt thereof, to a subject in need thereof:

wherein:
P is independently hydrogen or a protecting group;
A is substituted or unsubstituted carbocyclyl, substitut

Assignees

• Harvard College

Inventors

• Myers Andrew G
• Mitcheltree Matthew James
• Silvestre Katherine J

Classifications

• C07H15/14 Primary

  attached to a sulfur, selenium or tellurium atom of a saccharide radical · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• C07D491/052 Primary

  the oxygen-containing ring being six-membered · CPC title

• C07H15/16

  Lincomycin; Derivatives thereof · CPC title

• C07D491/04

  Ortho-condensed systems · CPC title