RUNX2 Transcription Factor Inhibitors and Uses Thereof

Patent metadata

Field	Value
Publication number	US-2019263751-A1
Application number	US-201916402402-A
Country	US
Kind code	A1
Filing date	May 3, 2019
Priority date	Mar 19, 2015
Publication date	Aug 29, 2019
Grant date	—

Abstract

Substituents R1 and R2 independently are H, Cl, F, Br, CH3, CF3, SH, —N(C1-3alkyl)2, —NHC(O)C1-3alkyl, or —NHC(O)C5-7cycloalkyl, substituent R3 is H or C1-3 alkyl and R4 is a bridged cycloalkene such as a bridged cyclohexene or a bridge-substituted cyclohexene. The compounds are therapeutics to treat a cancer, such as breast cancer, or metastatic cancers, to inhibit RUNX2 activity, such as protein expression, in a cancer cell and to increase survival of a subject with breast cancer.

First claim

What is claimed is:

1 . A compound having the chemical structure

wherein
R 1 and R 2 independently are H, Cl, F, Br, CH 3 , CF 3 , SH, —N(C 1-3 alkyl) 2 , —NHC(O)C 1-3 alkyl, or —NHC(O)C 5-7 cycloalkyl;
R 3 is H or C 1-3 alkyl; and
R 4 is

or
a pharmaceutically acceptable salt thereof.

2 . The compound of claim 1 , wherein R 3 is NH.

3 . The compound of claim 1 , wherein R 1 and R 2 are independently H, Cl, Br, or —NHC(O)CH 3 , R 3 is NH and R 4 is

4 . The compound of claim 1 , wherein R 1 and R 2 are independently H, Cl, CH 3 , —NHC(O)CH 3 , —NHC(O)cyclohexane, or —N(CH 3 ) 2 , R 3 is NH and R 4 is

5 . The compound of claim 1 , wherein R 1 and R 2 are each Cl and R 3 is NH.

6 . The compound of claim 1 , wherein the chemical structure is:

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

8 . A compound having the chemical structure:

or a pharmaceutically acceptable salt thereof.

9 . A pharmaceutical composition comprising the compound of claim 8 and a pharmaceutically acceptable carrier.

Assignees

• Univ Maryland
• Us Veterans Affairs

Inventors

• Passaniti Antonino
• Mackerell Jr Alexander D

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07C235/82 Primary

  with the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring · CPC title

• A61K31/196

  the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil · CPC title

• C07C2601/14

  The ring being saturated · CPC title

• C07C2602/42

  the bicyclo ring system containing seven carbon atoms · CPC title