Methods for polymorphic screening

Patent metadata

Field	Value
Publication number	US-12534827-B2
Application number	US-202117793730-A
Country	US
Kind code	B2
Filing date	Jan 14, 2021
Priority date	Jan 21, 2020
Publication date	Jan 27, 2026
Grant date	Jan 27, 2026

Abstract

A method for screening a target compound for polymorphic forms is provided. The method comprises providing a library of mixed-crystal seeds, each mixed-crystal seed consisting essentially of the target compound and at least one structural analog that is structurally analogous to the target compound; and for each mixed-crystal seed: introducing the mixed-crystal seed into a crystallization medium comprising the target compound, under conditions suitable for crystallization of the target compound; monitoring the formation of crystals of the target compound; and when formed, characterizing the crystals of the target compound.

First claim

The invention claimed is:

1 . A method for screening a target compound for polymorphic forms, the method comprising:
providing a library of mixed-crystal seeds, each mixed-crystal seed consisting essentially of the target compound and at least one structural analog that is structurally analogous to the target compound; and for each mixed-crystal seed:
introducing the mixed-crystal seed into a crystallization medium comprising the target compound, under conditions suitable for crystallization of the target compound;
monitoring the formation of crystals of the target compound; and
when formed, characterizing the crystals of the target compound.

2 . The method of claim 1 , wherein the library of mixed-crystal seeds is prepared by varying at least one of a chemical structure of the at least one structural analog and a molar ratio of the target compound and the at least one structural analog.

3 . The method of claim 1 , wherein each mixed-crystal seed comprises the target compound and the at least one structural analog in a molar ratio varying between 95:5 and 5:95.

4 . The method of claim 3 , wherein each mixed-crystal seed comprises the target compound and the at least one structural analog in a molar ratio between 75:25 and 25:75.

5 . The method of claim 1 , wherein each one of the at least one structural analog is one of an isostere of the target compound, an isomer of the target compound, a quasi-isostere of the target compound, an isomer of an isostere of the target compound, and an isomer of a quasi-isostere of the target compound.

6 . The method of claim 5 , wherein:
the isomer of the target compound is a constitutional isomer of the target compound, an enantiomer of the target compound, a diastereoisomer of the target compound, or an isotopic isomer of the target compound; the isomer of the isostere of the target compound is a constitutional isomer of the isostere of the target compound, an enantiomer of the isostere of the target compound, a diastereoisomer of the isostere of the target compound, or an isotopic isomer of the isostere of the target compound; and the isomer of the quasi-isostere of the target compound is a constitutional isomer of the quasi-isostere of the target compound, an enantiomer of the quasi-isostere of the target compound, a diastereoisomer of the quasi-isostere of the target compound, or an isotopic isomer of the quasi-isostere of the target compound.

7 . The method of claim 1 , wherein the crystallization medium comprises one of a solution of the target compound in a solvent, a melt of the target compound, a solid, a mixture of solids and a mixture of a melt of the target compound suspended in a liquid.

8 . The method of claim 7 , wherein crystallization of the target compound is performed by at least one of grinding and sublimation.

9 . The method of claim 1 , wherein monitoring the formation of crystals of the target compound comprises monitoring the formation of single crystals of the target compound suitable for single-crystal X-ray diffraction.

10 . The method of claim 1 , wherein characterizing the crystals of the target compound is performed by at least one of powder X-ray diffraction (PXRD), single-crystal X-ray diffraction (SC-XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Raman spectroscopy, and infrared spectroscopy.

11 . A method for crystallizing a target compound, the method comprising:
providing a mixed-crystal seed consisting essentially of the target compound and at least one structural analog that is structurally analogous to the target compound; and introducing the mixed crystal seed into a crystallization medium comprising the target compound, to obtain crystals of the target compound.

12 . The method of claim 11 , wherein the mixed-crystal seed comprises the target compound and the at least one structural analog in a molar ratio varying between 95:5 and 5:95.

13 . The method of claim 11 , wherein each one of the at least one structural analog is one of an isostere of the target compound, an isomer of the target compound, a quasi-isostere of the target compound, an isomer of an isostere of the target compound, and an isomer of a quasi-isostere of the target compound.

14 . The method of claim 13 , wherein:
the isomer of the target compound is a constitutional isomer of the target compound, an enantiomer of the target compound, a diastereoisomer of the target compound, or an isotopic isomer of the target compound; the isomer of the isostere of the target compound is a constitutional isomer of the isostere of the target compound, an enantiomer of the isostere of the target compound, a diastereoisomer of the isostere of the target compound, or an isotopic isomer of the isostere of the target compound; and the isomer of the quasi-isostere of the target compound is a constitutional isomer of the quasi-isostere of the target compound, an enantiomer of the quasi-isostere of the target compound, a diastereoisomer of the quasi-isostere of the target compound, or an isotopic isomer of the quasi-isostere of the target compound.

15 . The method of claim 11 , wherein the crystallization medium comprises one of a solution of the target compound in a solvent, a melt of the target compound, a solid, a mixture of solids and a melt of the target compound suspended in a liquid.

16 . The method of claim 15 , wherein crystallization of the target compound is performed by at least one of grinding and sublimation.

17 . The method of claim 11 , further comprising monitoring the formation of single crystals of the target compound suitable for single-crystal X-ray diffraction.

18 . The method of claim 15 , further comprising characterizing the crystals of the target compound.

19 . The method of claim 18 , wherein characterizing the crystals of the target compound is performed by at least one of powder X-ray diffraction (PXRD), single-crystal X-ray diffraction (SC-XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Raman spectroscopy, and infrared spectroscopy.

20 . The method of claim 1 , wherein the target compound is in the form of a neutral molecule, a compound in the form of a salt of a neutral compound, a compound in the form of a solvate of a neutral compound or a salt, or a compound in the form of a cocrystal of a neutral compound or a salt.

Assignees

• Univ Montreal

Inventors

• Levesque Alexandre
• Maris Thierry
• Wuest James

Classifications

• C30B29/68

  Crystals with laminate structure, e.g. "superlattices" · CPC title

• C30B29/54

  Organic compounds · CPC title

• C30B7/08

  by cooling of the solution · CPC title

• C40B30/10 Primary

  by measuring physical properties, e.g. mass · CPC title

• G01N2223/62

  powders · CPC title