Compounds and methods for treating gastrointestinal disease

Patent metadata

Field	Value
Publication number	US-12226489-B2
Application number	US-201917279864-A
Country	US
Kind code	B2
Filing date	Sep 26, 2019
Priority date	Sep 28, 2018
Publication date	Feb 18, 2025
Grant date	Feb 18, 2025

Abstract

The present disclosure relates to chemical moieties which, when bonded to pharmacophores, cause the pharmacophores to undergo first pass metabolism. By undergoing first pass metabolism, a pharmacophore may be made less bioavailable. Such compounds and related pharmaceutical compositions may be used for targeted treatment of diabetic and non-diabetic gastrointestinal disorders, with minimal systemic circulation beyond the gastrointestinal tract.

First claim

What is claimed is:

1. A compound, comprising a pharmacophore and a targeting moiety, wherein the targeting moiety causes the pharmacophore to undergo first pass metabolism; wherein the targeting moiety is selected from:

wherein n, p, and q are each independently integers from 1-4; and
m is an integer from 0-5; and
the pharmacophore is glucagon receptor antagonist NNC 250926 wherein NNC 250926, has the structure

2. The compound of claim 1 , wherein the targeting moiety causes the pharmacophore to undergo first pass metabolism in the liver.

3. The compound of claim 1 , wherein the systemic bioavailability is less than 1%.

4. The compound of claim 1 , wherein the targeting moiety is

5. The compound of claim 1 , wherein the targeting moiety is

6. The compound of claim 1 , wherein the targeting moiety is

7. The compound of claim 1 , wherein the pharmacophore and the targeting moiety are linked through a linking moiety.

8. The compound of claim 1 , having the structure:

or a pharmaceutically acceptable salt thereof.

9. The compound of claim 1 , having the structure:

or a pharmaceutically acceptable salt thereof.

10. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable excipient.

11. A method of administering a compound of claim 1 comprising administering an effective amount of the compound of claim 1 to a subject suffering from diabetes or a gastrointestinal disorder.

12. The method of claim 11 , wherein the subject is suffering from diabetes.

Assignees

• Univ California

Inventors

• El-Nachef Wael N

Classifications

• A61K47/55

  the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P1/00

  Drugs for disorders of the alimentary tract or the digestive system · CPC title

• A61K31/4152

  having oxo groups directly attached to the heterocyclic ring, e.g. antipyrine, phenylbutazone, sulfinpyrazone · CPC title

• A61K47/54

  the modifying agent being an organic compound · CPC title