Compounds and methods for inhibiting fascin
Provided are compounds, compositions and methods for inhibiting fascin activity or treating a condition or disorder mediated by fascin activity in a subject in need thereof.
1. A compound of Formula IV
or tautomer thereof, and/or a pharmaceutically acceptable salt thereof;
wherein
R 2 is 6- to 10-membered aryl or 5- to 10-membered heteroaryl; wherein the 6- to 10-membered aryl or 5- to 10-membered heteroaryl is optionally substituted with 1 to 4 R 4 , wherein each R 4 is independently selected from the group consisting of lower alkyl, lower haloalkyl, —OH, —OR 7 , —SH, —SR 7 , —NR 10 R 10 , halo, cyano, nitro, —COH, —COR 7 , —CO 2 H, —CO 2 R 7 , —CONR 10 R 10 , —OCOR 7 , —OCO 2 R 7 , —OCONR 10 R 10 , —NR 10 COR 10 , —NR 10 CO 2 R 10 , —SOR 7 , —SO 2 R 7 , SO 2 NR 10 R 10 , phenyl (optionally substituted with lower alkyl, halo or lower haloalkyl, or —OH), and —NR 10 SO 2 R 7 ;
each R 3 is independently selected from the group consisting of lower alkyl, lower haloalkyl, —OH, —OR 7 , —SH, —SR 7 , —NR 10 R 10 , halo, cyano, nitro, —COH, —COR 7 , —CO 2 H, —CO 2 R 7 , —CONR 10 R 10 , —OCOR 7 , —OCO 2 R 7 , —OCONR 10 R 10 , —NR 10 COR 10 , —NR 10 CO 2 R 10 , —SOR 7 , —SO 2 R 7 , SO 2 NR 10 R 10 , and —NR 10 SO 2 R 7 ;
m is 0, 1, 2 or 3;
R 7 is lower alkyl; and
each R 10 is independently hydrogen or lower alkyl, or two R 10 together with the atom(s) attached thereto form a 4- to 6-membered ring;
Y is selected from the group consisting of CF 3 , Cl, F and Me;
provided that the compound is not N-(1-(4-(trifluoromethyl)benzyl)-1H-indazol-3-yl)furan-2-carboxamide.
2. A compound of claim 1 , wherein R 2 is 5- or 6-membered heteroaryl optionally substituted with 1 to 4 R 4 .
3. A compound of claim 1 , wherein R 2 is optionally substituted with 1 to 4 R 4 , and R 2 is selected from the group consisting of furan, benzofuran, pyridine, pyridazine, pyrimidine, pyrazine, thiophene, thiazole, isothiazole, oxazole, isoxazole, oxadiazole, imidazole, pyrrole, and pyrazole.
4. A compound of claim 1 , wherein R 2 is selected from the group consisting of
5. A compound of claim 3 , wherein R 4 is not optional and is selected from the group consisting of lower alkyl, halo, lower haloalkyl, —OH, —OR 7 , cyano and phenyl optionally substituted methyl, and wherein R 7 is lower alkyl or lower haloalkyl.
6. A compound of claim 1 , wherein m is 0.
7. A compound selected from:
or tautomer thereof, and/or a pharmaceutically acceptable salt thereof.
8. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable carrier.
9. The compound of claim 7 , wherein the compound is
or tautomer thereof, and/or a pharmaceutically acceptable salt thereof.
10. The compound of claim 7 , wherein the compound is
or tautomer thereof, and/or a pharmaceutically acceptable salt thereof.
11. The compound of claim 7 , wherein the compound is
or tautomer thereof, and/or a pharmaceutically acceptable salt thereof.
12. The compound of claim 7 , wherein the compound is
or tautomer thereof, and/or a pharmaceutically acceptable salt thereof.
13. The compound of claim 7 , wherein the compound is
or tautomer thereof, and/or a pharmaceutically acceptable salt thereof.
14. The compound of claim 7 , wherein the compound is
or tautomer thereof, and/or a pharmaceutically acceptable salt thereof.
15. The compound of claim 1 , wherein
R 2 is selected from pyrrole, imidazole, isothiazole, isoxazole, pyrazole, pyrimidine and pyridazine, each of which may be optionally substituted by one or more methyl;
m is zero; and
Y is CF 3 ,
or tautomer thereof, and/or a pharmaceutically acceptable salt thereof.
16. The compound of claim 15 , wherein R 2 is substituted by one or two methyl moieties.
17. The compound of claim 1 , wherein R 2 is selected from the group consisting of
18. The compound of claim 17 , wherein R 2 is selected from the group consisting of
19. The compound of claim 17 , wherein m is zero.
20. The compound of claim 18 , wherein m is zero.