Compositions and methods for treating tuberculosis
The present invention provides compounds for the treatment of a bacterial infection. Additionally, the present invention provides compositions and methods for using these compounds and compositions in the treatment of a bacterial infection in a subject.
1. A compound having a structure of Formula (I) or a pharmaceutically acceptable salt thereof:
wherein, independently for each occurrence,
R 1 is unsubstituted lower alkyl;
R 2 is unsubstituted lower alkyl;
R 4 is selected from —C(O)NR 5 R 6 and —C(O)NHS(O 2 )R 7 ;
R 5 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, or substituted or unsubstituted heterocyclyl;
R 6 is hydrogen, hydroxyl, substituted or unsubstituted alkyl or substituted or unsubstituted cycloalkyl; or
R 5 and R 6 together with the nitrogen to which they are attached form a substituted or unsubstituted heterocyclyl;
R 7 is substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
Cy 1 is selected from substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; and
Cy 2 is selected from substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl.
2. The compound of claim 1 , wherein Cy 1 is selected from:
wherein R 3 is H or methyl.
3. The compound of claim 1 , wherein Cy 1 is selected from:
4. The compound of claim 1 , wherein Cy 1 is selected from: substituted or unsubstituted phenyl, furyl, thienyl, pyridinyl, pyrimidinyl, naphthyl, oxazolyl, pyrazolyl, piperidinyl, heterocycloalkenyl, cycloalkenyl, and imidazolyl.
5. The compound of claim 1 , wherein Cy 2 is selected from:
6. The compound of claim 1 , wherein Cy 2 is selected from: substituted or unsubstituted phenyl, pyridinyl, pyrazolyl, pyrimidinyl, cycloalkenyl, piperidinyl, morpholino, heterocycloalkenyl, and pyrrolidinyl.
7. A compound of claim 1 , wherein R 4 is selected from:
8. The compound of claim 1 , wherein Cy 1 is
9. The compound of claim 1 , wherein Cy 2 is
10. The compound of claim 1 , wherein R 4 is
11. The compound of claim 1 , wherein R 4 is not H.
12. The compound of claim 1 , wherein R 1 and R 2 are methyl.
13. A pharmaceutical composition comprising a compound of claim 1 .
14. A pharmaceutical composition according to claim 13 , further comprising one or more pharmaceutically acceptable excipients.
15. A method of treating a mycobacterial infection in a subject, comprising administering to the subject a compound having a structure of Formula (I) or a pharmaceutically acceptable salt thereof:
wherein, independently for each occurrence,
R 1 is unsubstituted lower alkyl,
R 2 is unsubstituted lower alkyl,
R 4 is selected from hydrogen, substituted or unsubstituted acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkylamino, amino, substituted or unsubstituted dialkylamino, sulfonamido, —C(O)OR 5 , —C(O)R 7 , —C(O)NR 5 R 6 , —C(O)NHS(O 2 )R 7 and —S(O 2 )R 7 ;
R 5 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, or substituted or unsubstituted heterocyclyl;
R 6 is hydrogen, hydroxyl, substituted or unsubstituted alkyl or substituted or unsubstituted cycloalkyl; or
R 5 and R 6 together with the nitrogen to which they are attached form a substituted or unsubstituted heterocyclyl;
R 7 is substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
Cy 1 is selected from substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; and
Cy 2 is selected from substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl.
16. The method of claim 15 , wherein the subject is a mammal.
17. The method of claim 15 , wherein the mycobacterial infection is caused by Mycobacterium abscessus, Mycobacterium avium complex, Mycobacterium goodii, Mycobacterium leprae, Mycobacterium lepraemurium, Mycobacterium lepromatosis, Mycobacterium mucogenicum, Mycobacterium neoaurum, Mycobacterium triplex , or Mycobacterium tuberculosis complex.
18. The method of claim 15 , wherein the compound is administered orally, nasally, buccally, sublingually, intramuscularly, intravenously, transmucosally, rectally, topically, transdermally, subcutaneously, or by inhalation.
19. The method of claim 15 , wherein R 4 is not H.
20. The method of claim 15 , wherein R 1 and R 2 are both methyl.