Substituted 1,3,4-oxadiazole derivatives as anti-tubercular agents

1. A method of treating tuberculosis in a patient, comprising administering to a patient in need thereof a therapeutically effective amount of a compound having the formula I:

or a pharmaceutically acceptable salt, ester, stereoisomer, or solvate thereof, wherein:

R, R 1 , and R 2 may be the same or different and are independently selected from the group consisting of hydrogen, halogen, nitro, and methyl.

2. The method of claim 1 , wherein R and R 2 are hydrogen and R 1 is chlorine, fluorine, or bromine.

3. The method of claim 1 , wherein R 2 is hydrogen, R is bromine or nitro, and R 1 is methyl.

4. The method of claim 1 , wherein R, R 1 , and R 2 are all be hydrogen.

5. The method of claim 1 , wherein R 2 is hydrogen, R 1 is bromine, and R is methyl.

6. The method of claim 1 , wherein R 1 and R 2 are hydrogen and R is fluorine.

7. The method of claim 1 , wherein R 2 is chlorine and either R or R 1 is hydrogen and the other of R and R 1 is chlorine.

8. The method of claim 1 , wherein the compound is selected from the group consisting of:

2-(1-(5-Chloro-2-methoxyphenyl)-5-methyl-1H-pyrazol-4-yl)-5-(4-chlorophenyl)-1,3,4-oxadiazole (7a);

2-(1-(5-Chloro-2-methoxyphenyl)-5-methyl-1H-pyrazol-4-yl)-5-(4-fluorophenyl)-1,3,4-oxadiazole (7b);

2-(3-Bromo-4-methylphenyl)-5-(1-(5-chloro-2-methoxyphenyl)-5-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazole (7c);

2-(1-(5-Chloro-2-methoxyphenyl)-5-methyl-1H-pyrazol-4-yl)-5-phenyl-1,3,4-oxadiazole (7d);

2-(4-Bromophenyl)-5-(1-(5-chloro-2-methoxyphenyl)-5-methyl-1Hpyrazol-4-yl)-1,3,4-oxadiazole (7e);

2-(4-Bromo-3-methylphenyl)-5-(1-(5-chloro-2-methoxyphenyl)-5-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazole (7f);

2-(1-(5-Chloro-2-methoxyphenyl)-5-methyl-1H-pyrazol-4-yl)-5-(3-fluorophenyl)-1,3,4-oxadiazole (7g);

2-(1-(5-Chloro-2-methoxyphenyl)-5-methyl-1H-pyrazol-4-yl)-5-(3,5-dichlorophenyl)-1,3,4-oxadiazole (7h);

2-(1-(5-Chloro-2-methoxyphenyl)-5-methyl-1H-pyrazol-4-yl)-5-(3,4-dichlorophenyl)-1,3,4-oxadiazole (7i);

2-(1-(5-Chloro-2-methoxyphenyl)-5-methyl-1H-pyrazol-4-yl)-5-(4-methyl-3-nitrophenyl)-1,3,4-oxadiazole (7j);

and a pharmaceutically acceptable salt, ester, stereoisomer, or solvate thereof.

9. The method of claim 1 , wherein the tuberculosis comprises multiple drug resistant (MDR) strains of Mycobacterium tuberculosis.

10. The method of claim 1 , wherein the tuberculosis comprises H37Rv strains of Mycobacterium tuberculosis.

11. A method of treating tuberculosis in a patient, comprising administering to a patient in need thereof a therapeutically effective amount of a compound having the formula I:

or a pharmaceutically acceptable salt, ester, stereoisomer, or solvate thereof, wherein:

R, R 1 , and R 2 may be the same or different and are independently selected from the group consisting of hydrogen, chlorine, fluorine, bromine, nitro, and methyl.

12. The method of claim 10 , wherein the tuberculosis comprises multiple drug resistant (MDR) strains of Mycobacterium tuberculosis.

13. The method of claim 10 , wherein the tuberculosis comprises H37Rv strains of Mycobacterium tuberculosis.

14. A method of treating tuberculosis in a patient, comprising administering to a patient in need thereof a therapeutically effective amount of a compound selected from the group consisting of:

2-(1-(5-Chloro-2-methoxyphenyl)-5-methyl-1H-pyrazol-4-yl)-5-(4-chlorophenyl)-1,3,4-oxadiazole (7a);

2-(1-(5-Chloro-2-methoxyphenyl)-5-methyl-1H-pyrazol-4-yl)-5-(4-fluorophenyl)-1,3,4-oxadiazole (7b);

2-(3-Bromo-4-methylphenyl)-5-(1-(5-chloro-2-methoxyphenyl)-5-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazole (7c);

2-(1-(5-Chloro-2-methoxyphenyl)-5-methyl-1H-pyrazol-4-yl)-5-phenyl-1,3,4-oxadiazole (7d);

2-(4-Bromophenyl)-5-(1-(5-chloro-2-methoxyphenyl)-5-methyl-1Hpyrazol-4-yl)-1,3,4-oxadiazole (7e);

2-(4-Bromo-3-methylphenyl)-5-(1-(5-chloro-2-methoxyphenyl)-5-methyl-1H-pyrazol-4-yl)-1,3,4-oxadiazole (7f);

2-(1-(5-Chloro-2-methoxyphenyl)-5-methyl-1H-pyrazol-4-yl)-5-(3-fluorophenyl)-1,3,4-oxadiazole (7g);

2-(1-(5-Chloro-2-methoxyphenyl)-5-methyl-1H-pyrazol-4-yl)-5-(3,5-dichlorophenyl)-1,3,4-oxadiazole (7h);

2-(1-(5-Chloro-2-methoxyphenyl)-5-methyl-1H-pyrazol-4-yl)-5-(3,4-dichlorophenyl)-1,3,4-oxadiazole (7i);

2-(1-(5-Chloro-2-methoxyphenyl)-5-methyl-1H-pyrazol-4-yl)-5-(4-methyl-3-nitrophenyl)-1,3,4-oxadiazole (7j);

and a pharmaceutically acceptable salt, ester, stereoisomer, or solvate thereof.

15. The method of claim 13 , wherein the tuberculosis comprises multiple drug resistant (MDR) strains of Mycobacterium tuberculosis.

16. The method of claim 13 , wherein the tuberculosis comprises H37Rv strains of Mycobacterium tuberculosis.