Ezrin inhibitors and methods of making and using

Patent metadata

Field	Value
Publication number	US-9522908-B2
Application number	US-201314047362-A
Country	US
Kind code	B2
Filing date	Oct 7, 2013
Priority date	Aug 21, 2010
Publication date	Dec 20, 2016
Grant date	Dec 20, 2016

Abstract

The invention encompasses compound and pharmaceutical composition comprising the compound of the following Formula (I): or pharmaceutically acceptable salts or prodrugs thereof, that are useful for inhibiting ezrin protein in a cell or for inhibiting the growth of a cancer cell.

First claim

What is claimed is:

1. A compound of

or pharmaceutically acceptable salts thereof,
wherein
E, F and G are present;

 is

wherein
D is H, OH, NO 2 , CN, carboxy, SH, CF 3 , C 1 to C 10 alkoxy, NH 2 , or NR 13 R 14 ; wherein R 13 and
R 14 are each independently H, C 1 to C 15 linear chain or branched chain alkyl;

E is —(CH 2 ) 2 —;
F is a bond, O, S,

 and
G is

wherein
R 1 and R 5 are each indepdently H, halogen, NO 2 , CN, carboxy, SH, CF 3 , C 1 to C 5 alkoxy, C 1 to C 5 alkyl group, NHCONH 2 , NH—SO 2 CH 3 , NH—NH—NH 2 , NH 2 , or NR 13 R 14 , and R 3 , R 6 -R 12 and X 1 -X 5 are each independently selected from H, halogen, OH, NO 2 , CN, carboxy, SH, CF 3 , C 1 to C 5 alkoxy, C 1 to C 5 alkyl group, NHCONH 2 , NH—SO 2 CH 3 , NH—NH—NH 2 , NH 2 , or NR 13 R 14 , and R 2 and R 4 are each independently selected from H, halogen, OH, NO 2 , CN, carboxy, SH, CF 3 , C 1 to C 5 alkyl group, NHCONH 2 , NH—SO 2 CH 3 , NH—NH—NH 2 , NH 2 , or NR 13 R 14 ;

with the proviso that when R 3 is OH and

 is

R 2 and R 4 are not both H, OH, or the same halogen.

2. The compound of claim 1 , wherein D is hydrogen.

3. The compound of claim 1 , wherein D is NH 2 or NR 13 R 14 .

4. The compound of claim 1 , wherein
D is H, F is a bond; and
G is

5. The compound of claim 1 , wherein R 3 is hydroxy or methoxy.

6. A method of inhibiting ezrin protein in a cell comprising administering to the cell the compound of claim 1 , or a pharmaceutically acceptable salt thereof.

7. A method of inhibiting the growth of a cancer cell comprising administering to the cell an amount of at least one compound of claim 1 wherein the cancer cell is an osteosarcoma cell or a lung cancer cell.

8. The method of claim 7 wherein the cancer cell is an osteosarcoma cell.

9. The method of claim 8 , wherein the osteosarcoma cell is in a subject.

10. The compound of claim 1 , wherein the compound is selected from the group consisting of

Assignees

• Univ Georgetown
• Gerogetown Univ

Inventors

• Brown Milton L
• Paige Mikell
• Torestsky Jeffrey A
• Uren Aykut
• Kosturko George
• Bulut Gullay

Classifications

• C07D215/24

  attached in position 8 · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D401/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D413/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D215/38

  Nitrogen atoms (nitro radicals C07D215/18) · CPC title