Thiadiazole compounds and methods of use

1. A compound of Formula I

wherein:

Y is —N(R 4 )R 5 or —OR 5 ;

X is —N(R 6 );

R 1 is a heteroaryl;

R 2 is H;

R 3 is selected from the group consisting of —(CR 7 R 8 ) t (aryl) and —(CR 7 R 8 ) t (heteroaryl);

R 4 is —H, C 1 -C 8 alkyl, —C(O)(CR 7 R 8 ) t )N(R 6 ) 2 , —C(O)(CR 7 R 8 ) t , —C(O) 2 (CR 7 R 8 ) t , —(CR 7 R 8 ) t (aryl), —(CR 7 R 8 ) t (heteroaryl), —(CR 7 R 8 ) t (cycloalkyl), or —(CR 7 R 8 ) t (heterocyclyl);

R 5 and R 6 are —H; and

R 7 and R 8 are independently selected from —H, C 1 -C 6 alkyl, and aryl;

wherein n is 1; m is 1; and each t is independently an integer from 1 to 3;

wherein each of the above alkyl, aryl, heteroaryl, cycloalkyl, and heterocyclyl moieties are optionally and independently substituted by 1-3 substituents selected from

amino,

aryl, heteroaryl, cycloalkyl, or heterocyclyl optionally substituted by 1-5 substituents selected from

C 1 -C 6 alkoxy,

C 1 -C 6 alkyl optionally substituted by halo,

aryl,

halo,

heteroaryl,

C 1 -C 6 hydroxyl, and

—NHS(O) 2 —(C 1 -C 6 alkyl);

C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkylamino,

C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl, wherein each of which may be interrupted by one or more hetero atoms,

cyano,

halo,

hydroxy,

nitro, or

—O-aryl;

or a pharmaceutically acceptable salt, hydrate, or stereoisomer thereof.

2. The compound of claim 1 or pharmaceutically acceptable salt, hydrate, or stereoisomer thereof, wherein t is 1.

3. The compound of claim 1 or pharmaceutically acceptable salt, hydrate, or stereoisomer thereof, wherein Y is —N(R 4 )(R 5 ).

4. The compound of claim 1 or pharmaceutically acceptable salt, hydrate, or stereolsomer thereof, wherein Y is —N(R 4 )(R 5 ), and t is 1.

5. The compound of claim 4 or pharmaceutically acceptable salt, hydrate, or stereoisomer thereof, wherein R 4 is —H, and R 7 and R 8 are independently selected from H and C 1 -C 3 alkyl.

6. The compound of claim 1 selected from

(S)-3-(3-Fluoro-phenyl)-N-[5-(3-methyl-1H-indazol-5-yl)-[1,3,4]thiadiazol-2-yl]-propane-1,2-diamine;

(S)-3-(3,4-Difluoro-phenyl)-N-[5-(3-methyl-1H-indazol-5-yl)-[1,3,4]thiadiazol-2-yl]-propane-1,2-diamine;

(S)-3-(3,4-Dichloro-phenyl)-N-[5-(3-methyl-1H-indazol-5-yl)-[1,3,4]thiadiazol-2-yl]-propane-1,2-diamine;

N-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propyl)-5-(3-methyl-1H-indazol-5-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(2-bromophenyl)propyl)-5-(3-methyl-1H-indazol-5-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(4-ethylphenyl)propyl)-5-(3-methyl-1H-indazol-5-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(3,5-difluorophenyl)propyl)-5-(3-methyl-1H-indazol-5-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(2-methoxyphenyl)propyl)-5-(3-methyl-1H-indazol-5-yl)-1,3,4-thiadiazol-2-amine;

(S)-3-(4-Methoxy-phenyl)-N-[5-(3-methyl-1H-indazol-5-yl)-[1,3,4]thiadiazol-2-yl]-propane-1,2-diamine;

(S)-3-(2-Chloro-phenyl)-N-[5-(3-methyl-1H-indazol-5-yl)-[1,3,4]thiadiazol-2-yl]-propane-1,2-diamine;

(S)-N-[5-(3-Methyl-1H-indazol-5-yl)-[1,3,4]thiadiazol-2-yl]-3-o-tolyl-propane-1,2-diamine;

(S)-N-[5-(3-Methyl-1H-indazol-5-yl)-[1,3,4]thiadiazol-2-yl]-3-(3-trifluoromethyl-phenyl)-propane-1,2-diamine;

(S)-3-(4-Fluoro-phenyl)-N-[5-(3-methyl-1H-indazol-5-yl)-[1,3,4]thiadiazol-2-yl]-propane-1,2-diamine;

(S)-3-(4-Chloro-phenyl)-N-[5-(3-methyl-1H-indazol-5-yl)-[1,3,4]thiadiazol-2-yl]-propane-1,2-diamine;

(S)-N-[5-(3-Methyl-1H-indazol-5-yl)-[1,3,4]thiadiazol-2-yl]-3-m-tolyl-propane-1,2-diamine;

N-((S)-2-amino-3-(3-bromophenyl)propyl)-5-(3-methyl-1H-indazol-5-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(3-chlorophenyl)propyl)-5-(3-methyl-1H-indazol-5-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(4-isopropylphenyl)propyl)-5-(3-methyl-1H-indazol-5-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(2,4-dichlorophenyl)propyl)-5-(3-methyl-1H-indazol-5-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-p-tolylpropyl)-5-(3-methyl-1H-indazol-5-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(naphthalen-2-yl)propyl)-5-(3-methyl-1H-indazol-5-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(benzo[b]thiophen-3-yl)propyl)-5-(3-methyl-1H-indazol-5-yl)-1,3,4-thiadiazol-2-amine

N-((S)-2-amino-3-(4-chlorophenyl)propyl)-5-(1H-indazol-5-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propyl)-5-(1H-indazol-5-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(naphthalen-2-yl)propyl)-5-(1H-indazol-5-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(4-isopropylphenyl)propyl)-5-(1H-indazol-5-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(3,4-dichlorophenyl)propyl)-5-(1H-indazol-5-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(2,4-dichlorophenyl)propyl)-5-(1H-indazol-5-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(4-methoxyphenyl)propyl)-5-(1H-indazol-5-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(4-bromophenyl)propyl)-5-(1H-indazol-5-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(3-(trifluoromethyl)phenyl)propyl)-5-(1H-indazol-5-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(3-(trifluoromethyl)phenyl)propyl)-5-(3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-3-(4-chlorophenyl)-2-(methylamino)propyl)-5-(3-methyl-1H-indazol-5-yl)-1,3,4-thiadiazol-2-amine;

5-(3-methyl-1H-indazol-5-yl)-N-((S)-2-(methylamino)-3-(3-(trifluoromethyl)phenyl)propyl)-1,3,4-thiadiazol-2-amine;

5-(1H-indazol-5-yl)-N-((S)-2-(methylamino)-3-(4-(trifluoromethyl)phenyl)propyl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(4-methoxyphenyl)propyl)-5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(3-(trifluoromethyl)phenyl)propyl)-5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propyl)-5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(3-methoxyphenyl)propyl)-5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(2,4-dichlorophenyl)propyl)-5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(4-chlorophenyl)propyl)-5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(3,5-difluorophenyl)propyl)-5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-m-tolylpropyl)-5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propyl)-5-(1,6-naphthyridin-2-yl)-1,3,4-thiadiazol-2-amine;

N-((S)-2-amino-3-(4-bromophenyl)propyl)-5-(3-methyl-1H-indazol-5-yl)-1,3,4-thiadiazol-2-amine;

N-((2S,3S)-2-amino-3-(4-(trifluoromethyl)phenyl)butyl)-5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-amine; and

N-((2S,3S)-2-amino-3-(4-(trifluoromethyl)phenyl)butyl)-5-(1H-indazol-5-yl)-1,3,4-thiadiazol-2-amine.

7. A pharmaceutical composition comprising a pharmaceutically-acceptable carrier and a compound of claim 1 .

8. The composition of claim 7 , further comprising at least one additional therapeutic agent, wherein the at least one additional therapeutic agent is an anti-cancer agent.