Carboxylic acid ester prodrug inhibitors of MEK

Patent metadata

Field	Value
Publication number	US-10654792-B2
Application number	US-201615383635-A
Country	US
Kind code	B2
Filing date	Dec 19, 2016
Priority date	Nov 15, 2012
Publication date	May 19, 2020
Grant date	May 19, 2020

Abstract

The invention generally relates to compounds having structure I:

wherein x represents alkyl, aryl or het-aryl, each of y independently represents hydrogen or halogen and z represents hydrogen or alkyl. Further, said compounds are inhibitors of MEK 1, 2 and 5. Furthermore, the invention includes methods of making said compounds, compositions including said compounds and uses for inhibiting MEK 1, 2 and 5.

First claim

The invention claimed is:

1. A method for preparing a compound of structure Ia or structure Ib:

the method comprising a reaction scheme selected from the group consisting of the following:

wherein: X 1 is hydrogen, X 2 is hydrogen, alkyl, aryl or hetaryl, Y 1 is halogen, Z is hydrogen or alkyl, and
Y 4 is fluorine, Y 5 is iodine, and Y 2 and Y 3 are hydrogen, or
Y 4 and Y 5 are hydrogen, and Y 2 and Y 3 are halogen.

2. The method of claim 1 , wherein Y 4 and Y 5 are hydrogen and Y 2 and Y 3 are fluorine.

3. The method of claim 1 , wherein Y 4 is fluorine, Y 5 is iodine, and Y 2 and Y 3 are hydrogen.

4. A method for preparing an inhibitor of mitogen-activated protein kinase 1, 2 and 5, of structure Ia or structure Ib:

the method comprising a reaction scheme selected from the group consisting of the following:

wherein: X 1 is hydrogen, X 2 is hydrogen, alkyl, aryl or hetaryl, Y 1 is halogen, Z is hydrogen or alkyl, and
Y 4 is fluorine, Y 5 is iodine, and Y 2 and Y 3 are hydrogen, or
Y 4 and Y 5 are hydrogen, and Y 2 and Y 3 are halogen.

5. The method of claim 4 , wherein Y 4 and Y 5 are hydrogen and Y 2 and Y 3 are fluorine.

6. The method of claim 4 , wherein Y 4 is fluorine, Y 5 is iodine, and Y 2 and Y 3 are hydrogen.

7. The method of claim 4 , wherein Y 1 and Y 4 are fluorine, Y 5 is iodine, and Y 2 and Y 3 are hydrogen.

Assignees

• Duquesne Univ Of The Holy Ghost
• Univ Holy Ghost Duquesne

Inventors

• Chakrabarty Suravi
• Monlish Darlene
• Flaherty Patrick
• Cavanaugh Jane E
• Potdar Sneha

Classifications

• C07C229/58 Primary

  having the nitrogen atom of at least one of the amino groups further bound to a carbon atom of a six-membered aromatic ring, e.g. N-phenyl-anthranilic acids · CPC title

• C07C227/10 Primary

  with simultaneously increasing the number of carbon atoms in the carbon skeleton · CPC title