Compounds and methods for inhibiting fascin

Patent metadata

Field	Value
Publication number	US-9573946-B2
Application number	US-201514626791-A
Country	US
Kind code	B2
Filing date	Feb 19, 2015
Priority date	Feb 20, 2014
Publication date	Feb 21, 2017
Grant date	Feb 21, 2017

Abstract

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.

First claim

What is claimed:

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 compo

Assignees

• Univ Cornell
• Novita Pharmaceuticals Inc

Inventors

• Huang Xin-Yun
• Shue Christy Young

Classifications

• A61P35/04

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• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P35/02

  specific for leukemia · CPC title