Compounds for treatment of cancer

Patent metadata

Field	Value
Publication number	US-10525037-B2
Application number	US-201816033953-A
Country	US
Kind code	B2
Filing date	Jul 12, 2018
Priority date	Mar 5, 2013
Publication date	Jan 7, 2020
Grant date	Jan 7, 2020

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 method of treating, suppressing, reducing the severity, reducing the risk, or inhibiting BRAF mutant cancer in a subject, comprising administering a composition comprising at least one of a BRAF inhibitor or a MEK inhibitor, in combination with 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 and a pharmaceutically acceptable carrier.

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

or pharmaceutically acceptable salts thereof or combination thereof.

3. The method of claim 1 , wherein said BRAF inhibitor is vemurafenib, dabrafenib or combination thereof, and said MEK inhibitor is trametinib or RO5068760, or combination thereof.

4. The method according to claim 1 , wherein the BRAF mutant cancer is BRAF inhibitor resistant cancer, melanoma, drug resistant melanoma, or taxane resistant cancer.

5. The method according to claim 4 , wherein said taxane is docetaxel.

6. The method according to claim 1 , wherein the MEK inhibitor is trametinib, selumetinib, RO5068760, MEK162, PD-325901, cobimetinib, CI-1040 or any combination thereof.

7. The method of claim 1 , wherein the cancer is melanoma, thyroid cancer, colorectal cancer, breast cancer, colon cancer, biliary tract cancer, non-small cell lung cancer (NSCLC), or ovarian cancer.

8. The method according to claim 1 , wherein the cancer is melanoma, thyroid cancer, colorectal cancer, or ovarian cancer.

9. The method according to claim 1 , wherein the cancer is melanoma.

10. The method according to claim 9 , wherein the melanoma is drug resistant melanoma.

11. The method according to claim 9 , wherein the melanoma is V600E positive melanoma.

Assignees

• Univ Tennessee Res Found

Inventors

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

Classifications

• A61P43/00

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

• A61P35/04

  specific for metastasis · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P17/00

  Drugs for dermatological disorders · CPC title