Substituted 3-azabicyclo[3.1.0]hexanes as ketohexokinase inhibitors

Patent metadata

Field	Value
Publication number	US-10988463-B2
Application number	US-202016999295-A
Country	US
Kind code	B2
Filing date	Aug 21, 2020
Priority date	Dec 29, 2015
Publication date	Apr 27, 2021
Grant date	Apr 27, 2021

Abstract

Provided herein are substituted 3-azabicyclo[3.1.0]hexanes as ketohexokinase inhibitors, processes to make said compounds, and methods comprising administering said compounds to a mammal in need thereof.

First claim

It is claimed:

1. A method of treating a disease for which an inhibitor of KHK is indicated, the method comprising the administration to a human in need thereof a therapeutically effective amount of a compound, wherein the compound is [(1R,5S,6R)-3-{2-[(2S)-2-methylazetidin-1-yl]-6-(trifluoromethyl)pyrimidin-4-yl}-3-azabicyclo[3.1.0]hex-6-yl]acetic acid, or pharmaceutically acceptable salt thereof, and wherein the disease is selected from any one or a combination of obesity, visceral adipose dysfunction, eating disorders, and excessive sugar craving.

2. The method of claim 1 , wherein the compound is a crystalline form of [(1R,5S,6R)-3-{2-[(2S)-2-methylazetidin-1-yl]-6-(trifluoromethyl)pyrimidin-4-yl}-3-azabicyclo[3.1.0]hex-6-yl]acetic acid.

3. The method of claim 2 , wherein the crystalline form is characterized substantially by the following principal powder x-ray diffraction pattern peaks expressed in terms of 2θ as measured with a copper radiation chosen from 9.0+/−0.2°, 10.4+/−0.2°, 15.0+/−0.2°, and 21.4+/−0.2°.

4. The method of claim 1 , wherein the compound is [(1R,5S,6R)-3-{2-[(2S)-2-methylazetidin-1-yl]-6-(trifluoromethyl)pyrimidin-4-yl}-3-azabicyclo[3.1.0]hex-6-yl]acetic acid.

5. The method of claim 4 , wherein the disease is obesity.

6. The method of claim 4 , wherein the disease is visceral adipose dysfunction.

7. The method of claim 4 , wherein the disease is eating disorders.

8. The method of claim 4 , wherein the disease is excessive sugar craving.

Assignees

• Pfizer

Inventors

• Dowling Matthew
• Fernando Dilinie
• Futatsugi Kentaro
• Huard Kim
• Magee Thomas Victor
• Raymer Brian
• Shavnya Andre
• Smith Aaron
• Thuma Benjamin
• Tsai Andy
• Tu Meihua

Classifications

• C07D403/14 Primary

  containing three or more hetero rings · CPC title

• C07D403/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D401/14 Primary

  containing three or more hetero rings · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P25/30

  for treating abuse or dependence · CPC title