Fused heterocyclic compounds and their use
The present invention provides compounds of formula (I) and pharmaceutically acceptable salts, hydrates and solvates thereof for use in the treatment of cancer:
1. A compound of formula (Ia) or a pharmaceutically acceptable salt thereof:
wherein:
X is O;
Y is selected from H, F, and Cl;
R 1 is selected from H, F, cyclopropyl, and —CH 2 —Z B ,
wherein Z B is selected from:
H, F, Cl, Me, —CH═CH 2 ,
—OR B1 , —NR B1 R B2 ,
-L B1 -OR B1A , -L B1 -NR B1A R B1B ,
—O-L B2 -OR B2A , —O-L B2 -NR B2A R B2B ,
—NH-L B2 -OR B2A , and —NH-L B2 -NR B2A R B2B
wherein:
R B1 and R B2 are each independently H or C 1-4 alkyl,
L B1 is C 1-3 alkylene,
R B1A and R B1B are each independently H or C 1-4 alkyl,
and L B2 is C 1-3 alkylene, and
R B2A and R B2B are each independently H or C 1-4 alkyl;
R 2 is selected from H, F, and Me; and
R 3 is selected from H, F and Me.
2. A compound according to claim 1 , wherein Y is H.
3. A compound according to claim 1 , wherein R 1 is selected from H and —CH 2 —Z B .
4. A compound according to claim 1 , wherein Z B is selected from H, F, Cl, Me, and —CH═CH 2 .
5. A compound according to claim 1 , wherein R 2 is H.
6. A compound according to claim 1 , wherein R 3 is H.
7. A compound according to claim 1 , which is a compound selected from the following compounds and pharmaceutically acceptable salts thereof:
Compound
Ref
Structure
IUPAC Name
1
6-(2-(4-fluorophenyl)thiazol-4- yl)benzo[d]oxazol-2(3H)-one
2
6-(2-(4-fluoro-2-methylphenyl)thiazol- 4-yl)benzo[d]oxazol-2(3H)-one
5
6-(2-(2-ethyl-4-fluorophenyl)thiazol-4- yl)benzo[d]oxazol-2(3H)-one
6
6-(2-(2-cyclopropyl-4- fluorophenyl)thiazol-4- yl)benzo[d]oxazol-2(3H)-one
7
6-(2-(2-allyl-4-fluorophenyl)thiazol-4- yl)benzo[d]oxazol-2(3H)-one
8
6-(2-(4-fluoro-2- (hydroxymethyl)phenyl)thiazol-4- yl)benzo[d]oxazol-2(3H)-one
9
6-(2-(4-fluoro-2-(2- hydroxyethyl)phenyl)thiazol-4- yl)benzo[d]oxazol-2(3H)-one
10
6-(2-(2-((benzyloxy)methyl)-4- fluorophenyl)thiazol-4- yl)benzo[d]oxazol-2(3H)-one
11
6-(2-(2,4-difluorophenyl)thiazol-4- yl)benzo[d]oxazol-2(3H)-one
12
6-(2-(4-fluoro-2- (fluoromethyl)phenyl)thiazol-4- yl)benzo[d]oxazol-2(3H)-one
13
6-(2-(4-fluoro-2- ((methylamino)methyl)phenyl)thiazol- 4-yl)benzo[d]oxazol-2(3H)-one
14
6-(2-(2-((dimethylamino)methyl)-4- fluorophenyl)thiazol-4- yl)benzo[d]oxazol-2(3H)-one
16
6-(2-(2-(2-(dimethylamino)ethyl)-4- fluorophenyl)thiazol-4- yl)benzo[d]oxazol-2(3H)-one
17
6-(2-(4-fluoro-2-((2- methoxyethoxy)methyl)phenyl)thiazol- 4-yl)benzo[d]oxazol-2(3H)-one
18
6-(2-(4-fluoro-2-((2- hydroxyethoxy)methyl)phenyl)thiazol- 4-yl)benzo[d]oxazol-2(3H)-one
19
6-(2-(2-((2-aminoethoxy)methyl)-4- fluorophenyl)thiazol-4- yl)benzo[d]oxazol-2(3H)-one
23
6-(2-(4-fluoro-3-methylphenyl)thiazol- 4-yl)benzo[d]oxazol-2(3H)-one
24
6-(2-(3,4-difluorophenyl)thiazol-4- yl)benzo[d]oxazol-2(3H)-one
25
6-(2-(4-fluoro-2,6- dimethylphenyl)thiazol-4- yl)benzo[d]oxazol-2(3H)-one
26
6-(2-(2,4-difluoro-3- methylphenyl)thiazol-4- yl)benzo[d]oxazol-2(3H)-one
27
6-(2-(3,4-difluoro-2- methylphenyl)thiazol-4- yl)benzo[d]oxazol-2(3H)-one.
8. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier, diluent, or excipient.
9. A compound according to claim 1 wherein Y is H, R 2 is H, and R 3 is H.
10. A compound according to claim 1 wherein R 1 is —CH 2 —Z B , and wherein Z B is selected from —OR B1 , —NR B1 R B2 , -L B1 -OR B1A , -L B1 -NR B1A R B1B , -L B1 -OR B1A , -L B1 -NR B1A R B1B , L B1 -R B1C , —O-L B2 -OR B2A , —O-L B2 -NR B2A R B2B , —O-L B2 -R B2C , —NH-L B2 -OR B2A , —NH-L B2 -NR B2A R B2B and —NH-L B2 -R B2C .
11. A compound according to claim 1 wherein R 1 is —CH 2 —Z B and wherein Z B is —O-L B2 -OR B2A .
12. A compound according to claim 1 wherein R 1 is —CH 2 —Z B and wherein Z B is —O—CH 2 CH 2 —O-Me.
13. A compound according to claim 1 which is a compound of formula
or a pharmaceutically acceptable salt thereof.