1,2,4-triazole derivatives, compositions, process of making and methods of use

1. A compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof:

wherein:

X is S;

R 1 is optionally substituted furan-C 1 alkyl;

R 2 is optionally substituted Ar—C 0-6 alkyl; and

R 3 is H, optionally substituted C 1-6 alkyl, C 3-6 alkenyl, or C 3-6 alkynyl.

2. The compound according to claim 1 , selected from the group consisting of:

5-(5-phenylamino-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-furan-2-carboxylic acid ethyl ester;

5-(5-phenylamino-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-furan-2-carbaldehyde;

5-(5-p-tolyl amino-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-furan-2-carboxylic acid ethyl ester;

5-(5-p-tolyl amino-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-furan-2-carbaldehyde;

5-(5-o-tolyl amino-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-furan-2-carboxylic acid ethyl ester;

5-(5-o-tolyl amino-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-furan-2-carbaldehyde;

3-(2-methyl-anilino)-5-(furan-3-ylmethylthio)-1,2,4-triazole;

3-(2-methoxy-anilino)-5-(furan-2-ylmethylthio)-1,2,4-triazole;

5-(5-(2-methoxyphenylamino)-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-furan-2-carboxylic acid ethyl ester

3-(2-methoxy-anilino)-5-(furan-3-ylmethylthio)-1,2,4-triazole;

5-(5-(3-methylphenylamino)-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-furan-2-carboxylic acid ethyl ester;

5-(5-(3-methylphenylamino)-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-furan-2-carbaldehyde;

3-(4-fluoro-anilino)-5-(furan-2-ylmethylthio)-1,2,4-triazole;

5-(5-(4-fluorophenylamino)-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-furan-2-carboxylic acid ethyl ester;

5-(5-(4-fluorophenylamino)-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-furan-2-carbaldehyde; and

3-(4-fluoro-anilino)-5-(furan-3-ylmethylthio)-1,2,4-triazole or a pharmaceutically acceptable salt or solvate thereof.

3. The compound according to claim 1 , selected from the group consisting of:

3-anilino-5-(furan-3-ylmethylthio)-1,2,4-triazole;

3-anilino-5-(furan-2-ylmethylthio)-1,2,4-triazole;

3-(2-methyl-anilino)-5-(furan-2-ylmethylthio)-1,2,4-triazole;

3-(3-methyl-anilino)-5-(furan-2-ylmethylthio)-1,2,4-triazole; and

3-(3-methyl-anilino)-5-(furan-3-ylmethylthio)-1,2,4-triazole; or

a pharmaceutically acceptable salt or solvate thereof.

4. The compound according to claim 1 , selected from the group consisting of:

3-(2-isopropyl-anilino)-5-(furan-2-ylmethylthio)-1,2,4-triazole;

5-(5-(2-isopropylphenylamino)-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-furan-2-carboxylic acid ethyl ester;

5-(5-(2-isopropyl amino)-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-furan-2-carbaldehyde;

3-(2-isopropyl-anilino)-5-(furan-3-ylmethylthio)-1,2,4-triazole;

3-(4-methyl-anilino)-5-(furan-2-ylmethylthio)-1,2,4-triazole; and

3-(4-methyl-anilino)-5-(furan-3-ylmethylthio)-1,2,4-triazole;

or a pharmaceutically acceptable salt or solvate thereof.

5. A pharmaceutical composition comprising the compound according to claim 1 , or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier.

6. A pharmaceutical composition comprising the compound according to claim 2 , or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier.

7. A pharmaceutical composition comprising the compound according to claim 3 , or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier.

8. A pharmaceutical composition comprising the compound according to claim 4 , or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier.

9. A method of making the compound of Formula (I) according to claim 1 , wherein X, R 1 , R 2 , and R 3 are as defined in claim 1 , comprising the steps of:

a) combining an isothiocyanate of Formula (II):

R 2 NCS (Formula II)

with thiourea to provide a compound of Formula (III):

b) treating the compound of Formula (III) with an alkyl halide under basic conditions to provide a compound of Formula (IV):

c) treating the compound of formula (IV) with hydrazine to provide a compound of Formula (V):

d) treating the compound of formula (V) with an alkyl halide under basic conditions to provide a compound of Formula (VI):

e) protecting the compound of formula (VI) to provide a compound of Formula (VII):

f) alkylating the compound of formula (VII) with an alkyl halide to provide a compound of Formula (VIII):

g) deprotecting the compound of formula (VIII) to provide the compound of Formula (I).