Pyrazole derivatives as inhibitors of STAT3

Patent metadata

Field	Value
Publication number	US-10138208-B2
Application number	US-201715643373-A
Country	US
Kind code	B2
Filing date	Jul 6, 2017
Priority date	Jun 14, 2012
Publication date	Nov 27, 2018
Grant date	Nov 27, 2018

Abstract

Compositions that modulate the activity of signal transducer and activator of transcription-3 (STAT3) activity as well as their methods of use, such as treatment and imaging are provided. Compositions contain small molecules such as substituted pyrazoles and are useful in treatment of diseases related to the activity of STAT3 including, for example, cancer and other diseases.

First claim

What is claimed is:

1. A compound selected from:

or a pharmaceutically acceptable salt thereof.

2. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

3. A method of inhibiting activation of STAT3 or initiating apoptosis in a cancer cell, wherein the cancer is selected from human colorectal carcinoma, lymphoma, leukemia, multiple myeloma, breast cancer, lung cancer, and brain cancer, the method comprising contacting the cell with a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

4. The method of claim 3 , wherein the brain cancer is selected from glioblastoma and medulloblastoma.

5. A method for treating cancer in a subject, wherein the cancer is selected from human colorectal carcinoma, lymphoma, leukemia, multiple myeloma, breast cancer, lung cancer, and brain cancer, the method comprising administering to the subject in need thereof a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

6. The method of claim 5 , wherein the brain cancer is selected from glioblastoma and medulloblastoma.

7. The method of claim 5 , wherein the compound is used in combination with an anti-cancer agent.

8. The method of claim 7 , wherein the anti-cancer agent is temozolomide.

9. The compound of claim 1 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

Assignees

• Mayo Found Medical Education & Res

Inventors

• Daniels David J
• Parney Ian F
• Peterson Timothy E

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/495

  having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53}) · CPC title

• A61K31/415

  1,2-Diazoles · CPC title

• C07D231/02

  not condensed with other rings · CPC title