Peripherally restricted GABA positive allosteric modulators for the treatment of irritable bowel syndrome and other ailments of the peripheral nervous system

Patent metadata

Field	Value
Publication number	US-10266534-B2
Application number	US-201515320866-A
Country	US
Kind code	B2
Filing date	Jun 26, 2015
Priority date	Jun 26, 2014
Publication date	Apr 23, 2019
Grant date	Apr 23, 2019

Abstract

The present invention provides compounds and compositions which are positive allosteric modulators of GABA-A receptors that selectively target the peripheral nervous system and organs of the body, and which do not pass through the blood-brain barrier. The compounds and compositions of the present invention are useful for treatment of diseases or disorders which are mediated by GABA-A neuronal activity, such as, for example, visceral pain, gut motility, irritable bowel syndrome, functional abdominal pain, functional idiopathic diarrhea, inflammatory bowel diseases, drug induced pain, bile salt malabsorption, lactase or other carbohydrate intolerance.

First claim

The invention claimed is:

1. A compound selected from the group consisting of:

2. A pharmaceutical composition comprising a compound of claim 1 , wherein the compound is selected from the group consisting of:

and a pharmaceutically acceptable carrier.

3. The pharmaceutical composition of claim 2 , further comprising at least one antibiotic agent selected from the group consisting of quinolone antibiotics trimethoprim-sulfamethoxazole antibiotics and combinations thereof.

4. A method for the inhibition of gut motility in a subject comprising administering to the subject a pharmaceutical composition of claim 2 .

5. A method for treatment of irritable bowel syndrome in a subject comprising administering to the subject a pharmaceutical composition of claim 2 .

6. A method for treatment of functional abdominal pain, functional idiopathic diarrhea, inflammatory bowel diseases, drug induced pain, bile salt malabsorption, lactase or other carbohydrate intolerance in a subject comprising administering to the subject a pharmaceutical composition of claim 2 .

7. A method for the inhibition of gut motility in a subject comprising administering to the subject a compound of claim 1 .

8. A method for treatment of irritable bowel syndrome in a subject comprising administering to the subject a compound of claim 1 .

9. A method for treatment of functional abdominal pain, functional idiopathic diarrhea, inflammatory bowel diseases, drug induced pain, bile salt malabsorption, lactase or other carbohydrate intolerance in a subject comprising administering to the subject a compound of claim 1 .

10. A method for the inhibition of gut motility in a subject comprising administering to the subject a compound having the following formula:

11. A method for treatment of irritable bowel syndrome in a subject comprising administering to the subject a compound having the following formula:

12. A method for treatment of functional abdominal pain, functional idiopathic diarrhea, inflammatory bowel diseases, drug induced pain, bile salt malabsorption, lactase or other carbohydrate intolerance in a subject comprising administering to the subject a compound having the following formula:

Assignees

• Univ Johns Hopkins
• Lieber Inst Inc

Inventors

• Pasricha Pankaj
• Huang Yifang
• Barrow James

Classifications

• A61P43/00

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

• A61P25/02

  for peripheral neuropathies · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61P1/12

  Antidiarrhoeals · CPC title

• A61P1/04

  for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants · CPC title