Crystalline form of hydrochloride salt of quinoline derivative

Patent metadata

Field	Value
Publication number	US-12545676-B2
Application number	US-202118005159-A
Country	US
Kind code	B2
Filing date	Jul 26, 2021
Priority date	Jul 28, 2020
Publication date	Feb 10, 2026
Grant date	Feb 10, 2026

Abstract

The present disclosure relates to a crystalline form of trans-4-[1-(3-Chloro-phenyl)-7-methoxy-2,4-dioxo-3,4-dihydro-2H-pyrimido[5,4-c]quinolin-3-yl]-cyclohexanecarboxylic acid hydrochloride, methods of preparation, and its use as a therapeutic agent to treat inflammatory diseases.

First claim

What is claimed is:

1 . A crystalline form of trans-4-[1-(3-Chloro-phenyl)-7-methoxy-2,4-dioxo-3,4-dihydro-2H-pyrimido[5,4-c]quinolin-3-yl]-cyclohexanecarboxylic acid hydrochloride, wherein the crystalline form is characterized as having an X-ray powder diffraction (XRPD) pattern comprising peaks at 11.6°±0.2°, 12.0°±0.2°, and 24.1°±0.2° measured using Cu Ka X-rays; and optionally
a first endothermic peak with an onset at about 231° C. and a second endothermic peak with an onset at about 354° C. or is characterized by a first endothermic peak with a peak at about 263° C. and a second endothermic peak with a peak at about 360° C. as determined by Differential Scanning calorimetry (DSC); or
a weight loss of about 0.8% wt/wt from about 25° C. to about 127° C. a weight loss of about 6.9% wt/wt from about 130° C. to about 300° C., a weight loss of about 1.7% wt/wt from about 300° C. to about 350° C. and/or a weight loss of about 9.5% from about 25° C. to about 350° C. as determined by Thermogravimetry Analysis (TGA); or
a solid-state 13 C Nuclear Magnetic Resonance (NMR) spectrum having peaks at 177.4, 161.9, 149.4, and 130.7 ppm, when the external reference of the carbonyl resonance of glycine is 176.5 ppm; or
a Fourier transform infrared (FT-IR) spectrum with peaks at 1679 and 1731 cm 1 .

2 . The crystalline form of claim 1 , wherein the crystalline form is characterized as having an X-ray powder diffraction (XRPD) pattern comprising peaks at 11.6°±0.2°, 12.0°±0.2°, and 24.1°±0.2° measured using Cu Ka X-rays; and a first endothermic peak with an onset at about 231° C. and a second endothermic peak with an onset at about 354° C. or is characterized by a first endothermic peak with a peak at about 263° C. and a second endothermic peak with a peak at about 360° C. as determined by Differential Scanning calorimetry (DSC).

3 . The crystalline form of claim 1 , wherein the crystalline form is characterized as having an X-ray powder diffraction (XRPD) pattern comprising peaks at 11.6°±0.2°, 12.0°±0.2°, and 24.1°±0.2°, measured using Cu Ka X-rays; and a weight loss of about 0.8% wt/wt from about 25° C. to about 127° C. a weight loss of about 6.9% wt/wt from about 130° C. to about 300° C. a weight loss of about 1.7% wt/wt from about 300° C. to about 350° C., and/or a weight loss of about 9.5% from about 25° C. to about 350° C. as determined by Thermogravimetry Analysis (TGA).

4 . The crystalline form of claim 1 , wherein the crystalline form is characterized as having an X-ray powder diffraction (XRPD) pattern comprising peaks at 11.6°±0.2°, 12.0°±0.2°, and 24.1°±0.2° measured using Cu Ka X-rays; and a solid-state 13 C Nuclear Magnetic Resonance (NMR) spectrum having peaks at 177.4, 161.9, 149.4, and 130.7 ppm, when the external reference of the carbonyl resonance of glycine is 176.5 ppm; or a Fourier transform infrared (FT-IR) spectrum with peaks at 1679 and 1731 cm 1.

5 . A crystalline form of trans-4-[1-(3-Chloro-phenyl)-7-methoxy-2,4-dioxo-3,4-dihydro-2H-pyrimido[5,4-c]quinolin-3-yl]-cyclohexanecarboxylic acid hydrochloride, wherein the crystalline form is characterized as having an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 1 ; and optionally
a Differential Scanning calorimetry (DSC) profile substantially the same as shown in FIG. 2 ; or a Thermogravimetry Analysis (TGA) profile substantially the same as shown in FIG. 3 ; or a solid-state 13 C Nuclear Magnetic Resonance (NMR) spectrum substantially the same as shown in FIG. 4 ; or a Fourier transform infrared (FT-IR) spectrum substantially the same as shown in FIG. 5 .

6 . The crystalline form of claim 1 , wherein the crystalline form is characterized as having an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 1 ; and a Differential Scanning calorimetry (DSC) profile substantially the same as shown in FIG. 2 .

7 . The crystalline form of claim 1 , wherein the crystalline form is characterized as having an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 1 ; and a Thermogravimetry Analysis (TGA) profile substantially the same as shown in FIG. 3 .

8 . The crystalline form of claim 1 , wherein the crystalline form is characterized as having an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 1 ; and a solid-state 13 C Nuclear Magnetic Resonance (NMR) spectrum substantially the same as shown in FIG. 4 ; or a Fourier transform infrared (FT-IR) spectrum substantially the same as shown in FIG. 5 .

9 . A crystalline form of trans-4-[1-(3-Chloro-phenyl)-7-methoxy-2,4-dioxo-3,4-dihydro-2H-pyrimido[5,4-c]quinolin-3-yl]-cyclohexanecarboxylic acid hydrochloride, wherein the crystalline form is characterized as having an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 1 ; and
a Differential Scanning calorimetry (DSC) profile substantially the same as shown in FIG. 2 ; or a Thermogravimetry Analysis (TGA) profile substantially the same as shown in FIG. 3 ; or a solid-state 13 C Nuclear Magnetic Resonance (NMR) spectrum substantially the same as shown in FIG. 4 ; or a Fourier transform infrared (FT-IR) spectrum substantially the same as shown in FIG. 5 .

10 . The crystalline form of claim 1 , wherein the crystalline form has a polymorphic purity of at least about 80%, or at least about 90%, or at least about 95%, or at least about 99%.

11 . A pharmaceutical composition comprising the crystalline form of claim 1 and a pharmaceutically acceptable carrier.

12 . A method for producing the crystalline form of claim 1 , the method comprising: a) mixing trans-4-[1-(3-Chloro-phenyl)-7-methoxy-2,4-dioxo-3,4-dihydro-2H-pyrimido[5,4-c]quinolin-3-yl]-cyclohexanecarboxylic or salt thereof in an aqueous solution comprising hydrochloric acid, where the aqueous solution has a temperature of at least 30° C.; and b) cooling the mixture to below 30° C.

13 . The method of claim 12 , wherein the aqueous solution comprising hydrochloric acid is 5 M HCl.

14 . The method of claim 12 , where the aqueous solution in step a) has a temperature of at least 50° C.

Assignees

• Vtv Therapeutics Llc

Inventors

• Gaddam Bapu
• Victory Samuel
• Polisetti Dharma Rao

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P17/06

  Antipsoriatics · CPC title

• A61P19/02

  for joint disorders, e.g. arthritis, arthrosis · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title