Isoquinolinyl triazolone complexes

Patent metadata

Field	Value
Publication number	US-11786608-B2
Application number	US-202117145006-A
Country	US
Kind code	B2
Filing date	Jan 8, 2021
Priority date	Mar 31, 2016
Publication date	Oct 17, 2023
Grant date	Oct 17, 2023

Abstract

Disclosed is a complex of a compound of Formula 1,a stereoisomer thereof, or a tautomer of the compound of Formula 1 or stereoisomer thereof, and a cyclodextrin, in which the complex is an amorphous solid. This disclosure also relates to materials and methods for preparing the complex, to pharmaceutical compositions which contain the complex, and to the use of the complex to treat Type I hypersensitivity reactions, autoimmune diseases, inflammatory disorders, cancer, non-malignant proliferative disorders, and other conditions associated with BTK.

First claim

What is claimed is:

1. A complex comprising a compound of Formula 1,

a stereoisomer thereof or a tautomer of the compound of Formula 1, and
a sulfobutylether β-cyclodextrin, wherein the complex is an amorphous solid.

2. The complex according to claim 1 , wherein the compound is (S)-3-(1-((1-acryloylpyrrolidin-3-yl)oxy)isoquinolin-3-yl)-1H-1,2,4-triazol-5(4H)-one or a tautomer thereof.

3. The complex according to claim 1 , wherein the compound is (R)-3-(1-((1-acryloylpyrrolidin-3-yl)oxy)isoquinolin-3-yl)-1H-1,2,4-triazol-5(4H)-one or a tautomer thereof.

4. The complex according to claim 1 , wherein the sulfobutylether β-cyclodextrin and the compound of Formula 1, stereoisomer or tautomer thereof are present in a molar ratio of about 1:1 to about 10:1.

5. The complex according to claim 1 , wherein the sulfobutylether β-cyclodextrin and the compound of Formula 1, stereoisomer or tautomer thereof are present in a molar ratio of about 1:1 to about 5:1.

6. The complex according to claim 1 , wherein the sulfobutylether β-cyclodextrin and the compound of Formula 1, stereoisomer or tautomer thereof are present in a molar ratio of about 1:1.

7. A pharmaceutical composition comprising a complex as defined in claim 1 , and a pharmaceutically acceptable excipient.

8. A method of making the complex of claim 1 comprising the compound of Formula 1,

a stereoisomer thereof or a tautomer of the compound of Formula 1, and a sulfobutylether β-cyclodextrin, wherein the complex is an amorphous solid, the method comprising:
atomizing a liquid solution into droplets, the liquid solution comprising the compound, stereoisomer, or tautomer of Formula 1, the sulfobutylether β-cyclodextrin, and water; and
removing at least a portion of the water from the droplets to form the complex.

9. The method according to claim 8 , wherein the liquid solution was obtained by dissolving the compound of Formula 1, stereoisomer or tautomer thereof in water having a pH of about 12 or greater.

10. The method according to claim 9 , wherein the liquid solution was obtained by dissolving the compound of Formula 1, stereoisomer or tautomer thereof in water having a pH of about 13 or greater.

11. The method according to claim 8 , wherein the pH of the liquid solution was adjusted to a pH of about 7 before atomizing the liquid solution into droplets.

Assignees

• Takeda Pharmaceuticals Co
• Chen Rongliang
• Manam Padma
• Zeng Lu

Inventors

• Chen Rongliang
• Manam Padma
• Zeng Lu

Classifications

• A61K47/6951 Primary

  using cyclodextrin (cyclodextrins used as simple excipients A61K47/40) · CPC title

• A61K31/4725

  containing further heterocyclic rings · CPC title

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title

• C07D401/14 Primary

  containing three or more hetero rings · CPC title

• C08B37/0015

  Inclusion compounds, i.e. host-guest compounds, e.g. polyrotaxanes · CPC title