Meropenem derivatives and uses thereof

Patent metadata

Field	Value
Publication number	US-11091487-B2
Application number	US-201916509388-A
Country	US
Kind code	B2
Filing date	Jul 11, 2019
Priority date	Mar 15, 2013
Publication date	Aug 17, 2021
Grant date	Aug 17, 2021

Abstract

The present invention provides novel derivative of β-lactam antibiotics, such as meropenem. The inventive compounds include compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. Also provided are particles (e.g., nanoparticles) and pharmaceutical compositions thereof that are mucus penetrating. The inventive particles and pharmaceutical compositions may be useful in delivering an inventive compound to the respiratory tract of a subject. The invention further provides methods of using and kits including the inventive compounds, particles thereof, and/or pharmaceutical compositions thereof for treating and/or preventing a pulmonary disease (e.g., a respiratory tract infection).

First claim

What is claimed is:

1. A compound having the formula:

or a salt thereof,
wherein
is a single bond or null,
is a single or double bond,
R B is —C(═O)—N(Me) 2 , —CH 2 —NH—S(═O) 2 —NH 2 , ═NH,

R A is substituted aliphatic, unsubstituted aliphatic, substituted heteroaliphatic, unsubstituted heteroaliphatic, substituted carbocyclyl, unsubstituted carbocyclyl, substituted heterocyclyl, unsubstituted heterocyclyl, substituted aryl, or unsubstituted aryl,
R C is substituted carbocyclyl, unsubstituted carbocyclyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, or unsubstituted heteroaryl, and
R F is hydrogen or methyl.

2. The compound of claim 1 , wherein R C is unsubstituted carbocyclyl, substituted aryl, or unsubstituted aryl.

3. The compound of claim 1 , wherein R C is unsubstituted carbocyclyl, aryl substituted with halogen, or unsubstituted aryl.

4. The compound of claim 1 , having the formula:

or a salt thereof,
wherein R C is

5. The compound of claim 1 , having the formula:

or a salt thereof,
wherein
R C is

6. The compound of claim 1 , having the formula:

or a salt thereof,
wherein
R C is

7. The compound of claim 1 , having the formula:

or a salt thereof,
wherein
R C is

8. The compound of claim 1 , having the formula:

or a salt thereof,
wherein
R C is

9. The compound of claim 1 , having the formula:

or a salt thereof,
wherein
R C is

10. A composition, comprising the compound of claim 1 .

11. A composition, comprising the compound of claim 2 .

12. A composition, comprising the compound of claim 3 .

13. A composition, comprising the compound of claim 4 .

14. A composition, comprising the compound of claim 5 .

15. A composition, comprising the compound of claim 6 .

16. A composition, comprising the compound of claim 7 .

17. A composition, comprising the compound of claim 8 .

18. A composition, comprising the compound of claim 9 .

19. A compound having the formula:

or a salt thereof,
wherein
is a single bond or null,
is a single or double bond,
R B is —C(═O)—N(Me) 2 , —CH 2 —NH—S(═O) 2 —NH 2 , ═NH,

R A is substituted aliphatic, unsubstituted aliphatic, substituted heteroaliphatic, unsubstituted heteroaliphatic, substituted carbocyclyl, unsubstituted carbocyclyl, substituted heterocyclyl, unsubstituted heterocyclyl, substituted aryl, or unsubstituted aryl,
R C is substituted carbocyclyl, unsubstituted carbocyclyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, or unsubstituted heteroaryl, and
R F is hydrogen.

20. A composition, comprising the compound of claim 19 .

21. A compound having the formula:

or a salt thereof,
wherein
is a single bond or null,
is a single or double bond,
R B is —CH 2 —NH—S(═O) 2 —NH 2 , ═NH,

R A is substituted aliphatic, unsubstituted aliphatic, substituted heteroaliphatic, unsubstituted heteroaliphatic, substituted carbocyclyl, unsubstituted carbocyclyl, substituted heterocyclyl, unsubstituted heterocyclyl, substituted aryl, or unsubstituted aryl,
R C is substituted aliphatic, unsubstituted aliphatic, substituted carbocyclyl, unsubstituted carbocyclyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, or unsubstituted heteroaryl, and
R F is hydrogen or methyl.

22. A composition, comprising the compound of claim 21 .

Assignees

• Kala Pharmaceuticals Inc

Inventors

• Ong Winston Zapanta
• Nowak Pawel Wojciech
• Kim Jinsoo
• Enlow Elizabeth M
• Bourassa James
• Cu Yen
• Popov Alexey
• Chen Hongming

Classifications

• A61K9/5015

  Organic compounds, e.g. fats, sugars · CPC title

• C07D477/20 Primary

  Sulfur atoms · CPC title

• A61K31/407

  condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K9/5123

  Organic compounds, e.g. fats, sugars · CPC title