Chemical compound for inhibition of SHP2 function and for use as an anti-cancer agent

Patent metadata

Field	Value
Publication number	US-9932288-B2
Application number	US-201615371699-A
Country	US
Kind code	B2
Filing date	Dec 7, 2016
Priority date	Dec 9, 2015
Publication date	Apr 3, 2018
Grant date	Apr 3, 2018

Abstract

This invention provides a compound that is 4,4′-(4′-Carboxy)-4-nonyloxy-[1,1′-biphenyl]-3,5-diyl)dibutanoic acid (CNBDA), derivative compounds of CNBDA, and pharmaceutical compositions thereof. The derivative compounds of CNBDA have one or more of the following substitutions (a) replacement of one or both of the carboxylic acid groups of the CNBDA compound with an organic acid group having 1-3, or 5-30, or more carbon atoms in chain length, wherein the carbon atom chains are either saturated, partially saturated, or unsaturated with respect to the carbon to carbon bonding, (b) replacement of the carboxylic groups of (a) with a phosphate, a sulphate, an amide, a hydroxyl, an aldehyde, or a halide group, and (c) replacement of the nonane group with an alkane having a carbon chain length of 1-8 or 10-30, or more carbon atoms. A method of treating a patient having cancer is provided.

First claim

We claim:

1. A compound that is 4,4′-(4′-Carboxy)-4-nonyloxy-[1,1′-biphenyl]-3,5-diyl)dibutanoic acid (abbreviated “CNBDA”) having the following chemical structure:

2. A compound that is a derivative of 4,4′-(4′-Carboxy)-4-nonyloxy-[1,1′-biphenyl]-3,5-diyl)dibutanoic acid (abbreviated “CNBDA”) having the following chemical structure:

wherein said derivative compound has one or more of the following substitutions (a) replacement of one or both of said butyric acid groups of the CNBDA compound with an organic acid group (carboxylic group) having from 1-3 carbon atoms in chain length, or having from 5 to 30carbon atoms in chain length, wherein the carbon atom chains are either saturated, partially saturated, or unsaturated with respect to the carbon to carbon bonding of said carbon atom chain, (b) replacement of said carboxylic groups with phosphate, sulphate, amide, hydroxyl, aldehyde, or halide groups, and (c) replacement of the nonane group with a carbon chain length having from 1-8 carbon atoms, or with a carbon chain length of ten to thirty carbon atoms in chain length.

3. A compound of the chemical formula:

wherein R 1 and R 2 are the same or different and are independently selected from the group of (a) an organic acid group (carboxylic group) having from 1-30 carbon atoms in chain length, wherein organic acid group is not a cyclic organic acid, wherein the carbon atom chains are either saturated, partially saturated, or unsaturated with respect to the carbon to carbon bonding of the carbon atom chain, and (b) replacement of the carboxylic groups of (a) with a phosphate, a sulphate, an amide, an hydroxyl, an aldehyde, or a halide group, and wherein R 3 is an alkyl group having from one to thirty carbon atoms in chain length.

4. A pharmaceutical composition comprising a compound of the chemical formula:

wherein R 1 and R 2 are the same or different and are independently selected from the group of (a) an organic acid group (carboxylic group) having from 1-30 carbon atoms in chain length, wherein the carbon atom chains are either saturated, partially saturated, or unsaturated with respect to the carbon to carbon bonding of the carbon atom chain, and (b) replacement of the carboxylic groups of (a) with a phosphate, a sulphate, an amide, an hydroxyl, an aldehyde, or a halide group, and wherein R 3 is an alkyl group having from one to thirty carbon atoms in chain length, and a pharmaceutically acceptable carrier.

5. The pharmaceutical composition of claim 4 wherein said pharmaceutically acceptable carrier is selected from the group consisting of dextrose, water, saline, isotonic saline, and lactose.

6. A pharmaceutical composition comprising a compound that is 4,4′-(4′-Carboxy)-4-nonyloxy-[1, 1 ′-biphenyl]-3, 5-diyl)dibutanoic acid (abbreviated “CNBDA”) having the following chemical structure:

and a pharmaceutically acceptable carrier.

7. A pharmaceutical composition that is a derivative of 4,4′-(4′-Carboxy)-4-nonyloxy-[1, 1′-biphenyl]-3 ,5-diyl)dibutanoic acid (abbreviated “CNBDA”) having the following chemical structure:

wherein said derivative compound has one or more of the following substitutions (a) replacement of one or both of said butyric acid groups of the CNBDA compound with an organic acid group (carboxylic group) having from 1-3 carbon atoms in chain length, or having from 5 to 30 carbon atoms in chain length, wherein the carbon atom chains are either saturated, partially saturated, or unsaturated with respect to the carbon to carbon bonding of said carbon atom chain, (b) replacement of said carboxylic groups with phosphate, sulphate, amide, hydroxyl, aldehyde, or halide groups, and (c) replacement of the nonane group with a carbon chain length having from 1-8 carbon atoms, or with a carbon chain length of ten to thirty carbon atoms in chain length.

8. The pharmaceutical composition of claim 6 wherein said pharmaceutically acceptable carrier is selected from the group consisting of dextrose, water, saline, isotonic saline, and lactose.

9. The pharmaceutical composition of claim 7 wherein said pharmaceutically acceptable carrier is selected from the group consisting of dextrose, water, saline, isotonic saline, and lactose.

Assignees

• Univ West Virginia

Inventors

• Agazie Yehenew
• Hartman Zachary

Classifications

• G01N33/5008

  for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics · CPC title

• G01N2333/916

  acting on ester bonds (3.1), e.g. phosphatases (3.1.3), phospholipases C or phospholipases D (3.1.4) · CPC title

• C12N2501/115

  Basic fibroblast growth factor (bFGF, FGF-2) · CPC title

• A61P9/06

  Antiarrhythmics · CPC title

• C12N2501/01

  Modulators of cAMP or cGMP, e.g. non-hydrolysable analogs, phosphodiesterase inhibitors, cholera toxin · CPC title