Crystalline PPAR-delta agonist
Inventors
DEL RIO GANCEDO, Susana • Suleiman, Osama • Sharp, Emma • BALOGH, Cristina • LEE, Rachael • MACRAE, Julie • Feeder, Neil
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11267795-B2
Publication Date
2022-03-08
Expiration Date
Abstract
Described herein is crystalline sodium (E)-2-(4-((3-(4-fluorophenyl)-3-(4-(3-morpholinoprop-1-yn-1-yl)phenyl)allyl)oxy)-2-methylphenoxy)acetate, uses of such crystalline material in the preparation of pharmaceutical compositions for the treatment of diseases or conditions that would benefit by administration with a PPARδ agonist compound.
Core Innovation
The document describes crystalline sodium (E)-2-(4-((3-(4-fluorophenyl)-3-(4-(3-morpholinoprop-1-yn-1-yl)phenyl)allyl)oxy)-2-methylphenoxy)acetate (Compound II) as a PPARδ agonist solid-state material. A particular solid form is identified as crystalline Form 1, and the material is characterized using XRPD, DSC, TGA, FTIR, and Raman spectroscopy, together with crystallographic unit-cell parameters at 100 K.
The disclosure addresses the need to define and distinguish specific solid forms of Compound II with reproducible solid-state characteristics. It provides multiple characterization patterns and threshold-defined features, including XRPD peak positions measured using Cu Kα radiation, DSC endotherm onset and peak values, and TGA behavior including a defined 0.1% w/w loss interval and degradation onset.
In addition to characterization, the document describes pharmaceutical compositions including oral solid forms containing the crystalline Compound II material, and treatment use for diseases or conditions benefiting from PPARδ agonism. It further includes further solid forms such as hydrates and solvates, an amorphous form of Compound II, and polymorph screening/conversion behavior involving moisture uptake, GVS and storage stability, and solvate formation/reversion.
Claims Coverage
The partial content includes three independent claims directed to crystalline Compound II in crystalline Form 1, each defining the form by XRPD-based characterization features, with one broader claim also requiring DSC, TGA, FTIR, Raman, and unit-cell parameters. A further dependent claim set refines the material form and extends to pharmaceutical compositions.
Crystalline form 1 defined by combined XRPD, DSC, TGA, FTIR, Raman, and unit-cell parameters
Crystalline sodium (E)-2-(4-((3-(4-fluorophenyl)-3-(4-(3-morpholinoprop-1-yn-1-yl)phenyl)allyl)oxy)-2-methylphenoxy)acetate (Compound II) wherein crystalline Compound II is crystalline Form 1, characterized by an XRPD pattern with peaks at about 2.8° 2-Theta, about 7.2° 2-Theta, about 13.4° 2-Theta, about 17.8° 2-Theta, about 19.7° 2-Theta, about 19.9° 2-Theta, and about 20.6° 2-Theta (Cu Kα); a DSC thermogram with an endotherm having onset at about 179.5° C. and peak at about 181.6° C.; a TGA pattern with a 0.1% w/w loss from 25 to 60° C. and degradation onset at about 250° C.; FTIR peaks at about 103 cm−1, about 838 cm−1, about 1220 cm−1, about 1504 cm−1, and about 1612 cm−1; Raman peaks at about 103 cm−1, about 126 cm−1, about 810 cm−1, about 1158 cm−1, about 1238 cm−1, about 1604 cm−1, and about 1629 cm−1; and unit cell parameters at 100 K including monoclinic crystal system and space group P2/c.
Crystalline form 1 defined by XRPD pattern as shown in FIG. 1
Crystalline Form 1 of sodium (E)-2-(4-((3-(4-fluorophenyl)-3-(4-(3-morpholinoprop-1-yn-1-yl)phenyl)allyl)oxy)-2-methylphenoxy)acetate (Compound II) characterized by an X-ray powder diffraction (XRPD) pattern as shown in FIG. 1.
Crystalline form 1 defined by Cu Kα XRPD peak positions
Crystalline Form 1 of sodium (E)-2-(4-((3-(4-fluorophenyl)-3-(4-(3-morpholinoprop-1-yn-1-yl)phenyl)allyl)oxy)-2-methylphenoxy)acetate (Compound II) characterized by an XRPD pattern with peaks at about 2.8° 2-Theta, about 7.2° 2-Theta, about 13.4° 2-Theta, about 17.8° 2-Theta, about 19.7° 2-Theta, about 19.9° 2-Theta, and about 20.6° 2-Theta as measured using Cu Kα radiation.
Claim coverage focuses on defining crystalline Compound II (crystalline Form 1) by specific XRPD signatures, with the broader independent claim further requiring DSC, TGA, FTIR, Raman, and unit-cell parameters at 100 K. The dependent claim set also refines the solid form and includes pharmaceutical compositions.
Stated Advantages
Documented Applications
No documented applications found
Interested in licensing this patent?