Moenomycin analogs, methods of synthesis, and uses thereof

• US 9,273,084 B2
• Filed: 04/05/2013
• Issued: 03/01/2016
• Est. Priority Date: 04/06/2012
• Status: Expired due to Fees

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Kahne, Daniel Evan, Kahne, Suzanne Walker, Tsukamoto, Hirokazu
• Primary Examiner(s): McIntosh, III, Traviss C
• Application Number:
  US14/390,811
• Publication Number:
  US 20150119354A1
• Time in Patent Office: 1,061 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: C07F 9/65586 at least one of the hetero rings does not contain nitrogen as ring hetero atom
• CPC Class Codes: C07H 1/00 Processes for the preparation of sugar derivatives
• CPC Class Codes: C07H 13/12 by acids having the group -X-C(=X)-X-, or halides thereof, in which each X means nitrogen, oxygen, sulfur, selenium or tellurium, e.g. carbonic acid, carbamic acid
• CPC Class Codes: C07H 5/06 Aminosugars

Abstract

The present invention provides compounds of Formula (I); or a pharmaceutically acceptable form thereof; wherein R¹,R²,R³,R⁶,R⁷,R¹²,R^a, and R^b are as defined herein, and G is a group of Formula (a), (b), or (c): Formula (II), wherein X₁; X₂, X₃, X₄, X₅, X₆, X₇, Y, R^C, R^d, R^z, a, d, e, x, n, and m are as defined herein. The present invention further provides pharmaceutical compositions comprising a compound of Formula (I), kits comprising such compositions, methods of use and treatment, and preparative methods.

Claims

1. A compound of Formula (I):

2. The compound of claim 1 of Formula (II):

3. The compound of claim 1 of Formula (III):

4. The compound of claim 1 of Formula (IV):

5. The compound of claim 1 wherein G is a group of Formula (a).

6. The compound of claim 5, wherein the group of Formula (a) is selected from the group consisting of:

7. The compound of claim 1 wherein G is a group of Formula (b).

8. The compound of claim 7 wherein at least one of X₁, X₂, X₃, X₄, X₅, X₆, and X₇ is halogen.

9. The compound of claim 7 wherein X₁ and X₂ are each hydrogen, X₃ and X₄ are each fluoro, and X₅, X₆, and X₇ are each fluoro.

10. The compound of claim 7, wherein the group of Formula (b) is selected from the group consisting of:

11. The compound of claim 1 wherein G is a group of Formula (c).

12. The compound of claim 11, wherein the group of Formula (c) is selected from the group consisting of:

13. The compound of claim 1 wherein G is selected from the group consisting of:

14. A pharmaceutical composition comprising an effective amount of a compound of claim 1, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, isomer, enantiomer, diastereomer, or polymorph thereof, and optionally a pharmaceutically acceptable excipient.

15. A method of treating a bacterial infection comprising administering to a subject an effective amount of a compound of claim 1, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, isomer, enantiomer, diastereomer, or polymorph thereof.

16. The method of claim 15, wherein the bacterial infection being treated is caused by Gram-positive bacteria.

17. The method of claim 15, wherein bacterial infection being treated is caused by Gram-negative bacteria.

18. The method of claim 15, wherein bacterial infection being treated is caused by vancomycin-resistant bacteria.

19. The method of claim 15, wherein bacterial infection being treated is caused by methicillin-resistant bacteria.

20. An in vitro method of inhibiting bacterial growth by contacting a bacterium with an effective amount of a compound of claim 1, or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, isomer, enantiomer, diastereomer, or polymorph thereof.

21. The method of claim 15, wherein the bacterial infection being treated is caused by vancomycin-resistant Staphylococcus aureus, vancomycin-resistant Enterococci, or methicillin-resistant Staphylococcus aureus.

22. The compound of claim 1, wherein the compound is of Formula (I):

23. A pharmaceutical composition comprising an effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof, and optionally a pharmaceutically acceptable excipient.

24. A method of treating a bacterial infection comprising administering to a subject an effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.