Compounds for treatment of cancer

Patent metadata

Field	Value
Publication number	US-10022356-B2
Application number	US-201414773265-A
Country	US
Kind code	B2
Filing date	Mar 5, 2014
Priority date	Mar 5, 2013
Publication date	Jul 17, 2018
Grant date	Jul 17, 2018

Abstract

The present invention relates to pharmaceutical compositions for treating cancer comprising BRAF inhibitors, (e.g. vemurafenib) and/or MEK inhibitor, (e.g. trametinib, RO5068760), in combination with anti-tubulin compounds of the invention or other known tubulin inhibitors, and using such compositions for treating cancer such as melanoma, drug-resistant cancer, and cancer metastasis.

First claim

What is claimed:

1. A pharmaceutical composition comprising (a) a tubulin inhibitor (b) at least one of a BRAF inhibitor, and (c) a pharmaceutically acceptable carrier, wherein the tubulin inhibitor is a compound represented by the structure of formula II:

wherein
A is single or fused aromatic or heteroaromatic ring system;
R 1 is H, C 1 -C 6 linear or branched alkyl, aryl, phenyl, benzyl, haloalkyl, aminoalkyl, —OCH 2 Ph, SO 2 -aryl, SO 2 -phenyl, —(C═O)-aryl, —(C═O)-phenyl or OH;
R 4 and R 5 are each independently hydrogen, C 1 -C 6 linear or branched alkyl, C 1 -C 6 linear or branched haloalkyl, C 1 -C 6 linear or branched alkoxy, C 1 -C 6 linear or branched haloalkoxy, F, Cl, Br, I, CF 3 , CN, —CH 2 CN, NH 2 , OH, —OC(O)CF 3 , alkylamino, aminoalkyl, —OCH 2 Ph, —NHCO— alkyl, COOH, —C(O)Ph, C(O)O-alkyl, C(O)H, —C(O)NH 2 or NO 2 ; and
n is an integer between 1-4;
or its pharmaceutically acceptable salt, N-oxide, hydrate, tautomer or isomer.

2. The composition of claim 1 , wherein said compound of formula II is:

or a pharmaceutically acceptable salt thereof, or a combination thereof.

3. The composition of claim 1 , wherein said BRAF inhibitor is vemurafenib, dabrafenib, GDC-0879, PLX-4720, sorafenib tosylate, LGX818 or any combination thereof.

4. The composition of claim 2 , comprising a compound represented by the following structure:

or a pharmaceutically acceptable salt thereof,
in combination with a BRAF inhibitor and a pharmaceutically acceptable carrier, wherein said BRAF inhibitor is vemurafenib.

Assignees

• Univ Tennessee Res Found

Inventors

• Wang Jin
• Chen Jianjun
• Miller Duane D
• Li Wei

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P43/00

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

• A61P35/04

  specific for metastasis · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P17/00

  Drugs for dermatological disorders · CPC title