Polycyclic LPA1 antagonist and uses thereof

Patent metadata

Field	Value
Publication number	US-9556133-B2
Application number	US-201113992022-A
Country	US
Kind code	B2
Filing date	Dec 7, 2011
Priority date	Dec 7, 2010
Publication date	Jan 31, 2017
Grant date	Jan 31, 2017

Abstract

Described herein is the LPA1 antagonist 1-{4′-[3-methyl-4-((R)-1-phenyl-ethoxycarbonylamino)-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid (Compound 1), or pharmaceutically acceptable salts thereof. Also described are methods of preparing the LPA1 antagonist, or pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions suitable for administration to a mammal that include the LPA1 antagonist, or pharmaceutically acceptable salt thereof, and methods of using such pharmaceutical compositions for treating LPA-dependent or LPA-mediated diseases or conditions.

First claim

What is claimed is:

1. A crystalline form of sodium salt of 1-{4′-[3-methyl-4-((R)-1-phenyl-ethoxycarbonylamino)-isoxazol-5-yl]-biphe-nyl-4-yl}-cyclopropanecarboxylic acid, wherein said crystalline form is a hydrate for use in a therapeutically effective amount in a pharmaceutical formulation wherein the crystalline form:
(a) has an X-ray powder diffraction (XRPD) pattern derived using Cu Kα radiation with characteristic peaks at 13.2° 2-Theta, 17.2° 2-Theta, 19.3° 2-Theta, 22.4° 2-Theta, and 25.6° 2-Theta;
(b) has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 4 ;
(c) has a DSC or a thermo-gravimetric analysis (TGA) substantially similar to the ones set forth in FIG. 5 and FIG. 6 ;
(d) has an infrared spectrum substantially similar to the one set forth in FIG. 7 ;
(e) was obtained from methyl ethyl ketone, acetonitrile, 1,4-dioxane/tert-butyl methyl ether, methyl ethyl ketone (MEK)/tert-butyl methyl, or ethanol/heptane;
(f) unit cell parameters substantially equal to the following at 25°:

a(Å)
13.8714(2)

b(Å)
 7.7379(2)

c(Å)
25.5253(5)

α°
90

β°
103.863(1)

γ°
90

V(Å3)
2659.96(9)

Z
4

Calculated Density
1.305

Crystal System
Monoclinic

SG
P2 1

R1
0.0301

Sol. Sites
1H 2 0

or (g) combinations thereof.

2. A pharmaceutical composition comprising the crystalline form of claim 1 , and at least one inactive ingredient selected from pharmaceutically acceptable carriers, diluents and excipients.

Assignees

• Brittain Jason Edward
• Seiders Thomas Jon
• King Christopher David
• Rosso Victor W
• Bristol Myers Squibb Co
• Amira Pharmaceuticals Inc

Inventors

• Brittain Jason Edward
• Seiders Thomas Jon
• King Christopher David
• Rosso Victor W

Classifications

• C07D261/14 Primary

  Nitrogen atoms · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P43/00

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

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title