Heterocyclic amides with anti-tuberculosis activity

• US 20050222408A1
• Filed: 01/27/2005
• Published: 10/06/2005
• Est. Priority Date: 07/14/2003
• Status: Abandoned Application

• Current Assignee: Colorado State University Research Foundation, University of Tennessee Research Foundation (University of Tennessee)
• Original Assignee: University of Tennessee Research Foundation (University of Tennessee)
• Inventors: Lee, Richard E., Yendapally, Raghunandan, Tangallapally, Rajendra Prasad, McNeil, Michael, Lenaerts, Anne
• Application Number:
  US11/044,420
• Publication Number:
  US 20050222408A1
• Time in Patent Office: Days
• US Class Current: 544/60
• CPC Class Codes: C07D 405/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links

Abstract

Compounds having the general structure:
wherein A is selected from the group consisting of oxygen, sulfur, and NR₁₅, and R₁₅ is selected from the group consisting of H, alkyl, aryl, substituted alkyl, and substituted aryl; B,D, and E are each independently selected from the group consisting of CH, nitrogen, sulfur and oxygen; R₁ is selected from the group consisting of nitro, halo, alkyl ester, arylsulfanyl, arylsulfinyl, arylsulfonyl and sulfonic acid; t is an integer from 1 to 3; and X is a substituted amide, and methods of using the novel compounds for treating infections caused by microorganisms, including Mycobacterium tuberculosis.

Claims

1. A compound having the general formula:

2. The compound of claim 1, wherein Y is

3. The compound of claim 2, wherein n is 1 and R₄ is hydrogen.

4. The compound of claim 2 wherein J is —

(CH₂)_q—

CH═

N— and

q is 0.

5. The compound of claim 2, wherein Z₁ is NR₅ and R₅ is an alkyl.

6. The compound of claim 2, wherein the compound is

7. The compound of claim 1, wherein Y is

8. The compound of claim 7, wherein Z₂ is NR₁₀ and R₁₀ is a substituted aryl.

9. The compound of claim 8, wherein R₁₀ is

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

11. The compound of claim 1, wherein Y is

12. The compound of claim 11, wherein Q is —

C(═

O)—

.

13. The compound of claim 11, wherein R₁₃ is selected from the group consisting of a halo an alkoxyl.

14. The compound of claim 11, wherein the compound is selected from the group consisting of:

15. A method of inhibiting the growth of a microorganism comprising contacting the microorganism with an effective amount of a compound having the general formula:

16. The method of claim 15, wherein the microorganism is Mycobacterium tuberculosis.

17. The method of claim 15, wherein the effective amount of the compound is about 1 to about 1000 micrograms per milliliter.

18. A method of treating a microbial infection in a subject comprising administering to the subject a therapeutically effective amount of the compound having the following general formula:

19. The method of claim 18, wherein the microbial infection is a Mycobacterium tuberculosis infection.

20. The method of claim 18, wherein the therapeutically effective amount is about 1 to about 1000 micrograms per milliliter.

21. A pharmaceutical formulation, comprising a compound having the following general structure in a pharmaceutically acceptable carrier: