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EP-4737447-A1 - CRYSTAL FORM OF BAXDROSTAT, AND PREPARATION METHOD THEREFOR AND USE THEREOF

EP4737447A1EP 4737447 A1EP4737447 A1EP 4737447A1EP-4737447-A1

Abstract

A new crystal form of Baxdrostat, and a preparation method therefor, a pharmaceutical composition containing the crystal form, and the use of the crystal form in the preparation of an aldosterone synthase inhibitor drug and a drug for treating hypertension, primary aldosteronism, and chronic kidney disease.

Inventors

  • ZHAI, Xiaoting
  • MENG, LIPING

Assignees

  • Crystal Pharmaceutical (Suzhou) Co., Ltd.

Dates

Publication Date
20260506
Application Date
20240628

Claims (9)

  1. A crystalline form of Compound I,
  2. The crystalline form of Compound I according to claim 1, wherein the X-ray powder diffraction pattern comprises at least one characteristic peak at 2theta values of 8.1°±0.2°, 14.3°±0.2° and 21.7°±0.2° using Cu-Kα radiation.
  3. The crystalline form of Compound I according to claim 1, wherein the X-ray powder diffraction pattern comprises at least one characteristic peak at 2theta values of 15.9°±0.2°, 18.9°±0.2° and 24.8°±0.2° using Cu-Kα radiation.
  4. The crystalline form of Compound I according to claim 1, wherein the X-ray powder diffraction pattern comprises characteristic peak at 2theta values of 14.7°±0.2°, 17.4°±0.2°, 18.5°±0.2° and 22.0°±0.2° using Cu-Kα radiation.
  5. The crystalline form of Compound I according to claim 1, wherein the X-ray powder diffraction pattern is substantially as depicted in Figure 1 using Cu-Kα radiation.
  6. The crystalline form of Compound I according to claim 1, wherein it is a hydrate.
  7. A pharmaceutical composition, wherein said pharmaceutical composition comprises a therapeutically effective amount of crystalline form of Compound I according to claim 1, and pharmaceutically acceptable excipients.
  8. Crystalline form of Compound I according to claim 1 for use of preparing aldosterone synthase inhibitor drugs.
  9. Crystalline form of Compound I according to claim 1 for use of preparing drugs treating hypertension, primary aldosteronism and chronic kidney disease.

Description

TECHNICAL FIELD The present disclosure pertains to the field of chemical crystallography, particularly relates to crystalline form of Baxdrostat, preparation method and use thereof. BACKGROUND Baxdrostat is an aldosterone synthase inhibitor developed by CinCor, and is used for the treatment of hypertension, primary aldosteronism and chronic kidney disease. Positive results have been achieved in phase II clinical trial for resistant hypertension. The chemical name of Baxdrostat is (+)-(R)-N-(4-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8-tetrahydroisoquinolin-8-yl)propionamide (hereinafter referred to as Compound I), and the structural formula is as follows: A crystalline form is a solid material whose constituents are arranged in a highly ordered microscopic structure, forming a crystal lattice that extends in all directions. Polymorphism refers to the phenomenon that a compound exists in more than one crystalline form. Compounds may exist in one or more crystalline forms, but their existence and characteristics cannot be predicted with any certainty. Different crystalline forms of active pharmaceutical ingredient (API) have different physicochemical properties, which can affect drug's in vivo dissolution and absorption and will further affect drug's clinical efficacy and safety to some extent. In particular, for some poorly soluble oral solid or semi-solid dosage forms, crystalline forms can be crucial to the performance of drug products. In addition, the physiochemical properties of a crystalline form, such as fluidity, compressibility, and grinding stability, are very important to the manufacturing process. Therefore, polymorphism is an important part of drug research and drug quality control. WO2013041591A1 discloses the synthesis method of Compound I, but does not disclose a crystalline form of Compound I. The inventors of the present disclosure surprisingly discovered a crystalline form of Compound I, which have advantages in hygroscopicity and stability, and is of great significance for the development of drugs containing Compound I. SUMMARY The present disclosure is to provide a crystalline form of Compound I, preparation method and pharmaceutical compositions comprising the crystalline form. According to the objective of the present disclosure, a crystalline form of Compound I is provided. According to the objective of the present disclosure, a hydrate of Compound I is provided. According to the objective of the present disclosure, crystalline form CSI of Compound I is provided (hereinafter referred to as Form CSI). The X-ray powder diffraction pattern of Form CSI comprises one or two or three characteristic peaks at 2theta values of 8.1°±0.2°, 14.3°±0.2° and 21.7°±0.2°. Preferably, the X-ray powder diffraction pattern of Form CSI comprises characteristic peaks at 2theta values of 8.1°±0.2°, 14.3°±0.2° and 21.7°±0.2° using CuKα radiation. The X-ray powder diffraction pattern of Form CSI comprises one or two or three characteristic peaks at 2theta values of 15.9°±0.2°, 18.9°±0.2° and 24.8°±0.2°. Preferably, the X-ray powder diffraction pattern of Form CSI comprises characteristic peaks at 2theta values of 15.9°±0.2°, 18.9°±0.2° and 24.8°±0.2° using CuKα radiation. The X-ray powder diffraction pattern of Form CSI comprises one or two or three or four characteristic peaks at 2theta values of 14.7°±0.2°, 17.4°±0.2°, 18.5°±0.2° and 22.0°±0.2°. Preferably, the X-ray powder diffraction pattern of Form CSI comprises characteristic peaks at 2theta values of 14.7°±0.2°, 17.4°±0.2°, 18.5°±0.2° and 22.0°±0.2° using CuKα radiation. The X-ray powder diffraction pattern of Form CSI comprises one or two or three or four or five or six or seven or eight or nine or ten or eleven or twelve or thirteen or fourteen or fifteen or sixteen characteristic peaks at 2theta values of 8.1°±0.2°, 14.3°±0.2°, 21.7°±0.2°, 15.9°±0.2°, 18.9°±0.2°, 24.8°±0.2°, 14.7°±0.2°, 17.4°±0.2°, 18.5°±0.2°, 22.0°±0.2°, 12.4°±0.2°, 16.3°±0.2°, 16.8°±0.2°, 20.1°±0.2°, 21.1°±0.2° and 24.5°±0.2°. Without any limitation being implied, the XRPD pattern of Form CSI is substantially as depicted in Figure 1 using CuKα radiation. Without any limitation being implied, the DSC curve of Form CSI is substantially as depicted in Figure 2. There is an endothermic peak near 103 °C, which is the dehydration signal of Form CSI. Without any limitation being implied, Form CSI is a hydrate. Without any limitation being implied, Form CSI shows about 3%~6% weight loss when heated to 150 °C by TGA. Without any limitation being implied, the TGA curves of Form CSI are substantially as depicted in Figure 4, Figure 5 and Figure 6, which show 3.2%, 5.0% and 5.1% weight loss when heated to 150 °C, respectively. According to the objective of the present disclosure, a process for preparing Form CSI is also provided. The process comprises: Placing Compound I in a mixed solvent of methanol and methyl tert-butyl ether, stirring, and separating to obtain Form CSI. Acco