Quinazolin crotyl compound dimaleate crystals and preparation methods and uses thereof

• US 10,640,470 B2
• Filed: 06/25/2018
• Issued: 05/05/2020
• Est. Priority Date: 05/05/2015
• Status: Active Grant

• Current Assignee: Hangzhou Huadong Medicine Group Biopharmaceutical Co. Ltd.
• Original Assignee: Hangzhou Huadong Medicine Group Biopharmaceutical Co. Ltd.
• Inventors: Lv, Yubin, Yin, Jianming, Huang, Xuehui, Li, Bangliang
• Primary Examiner(s): Carcanague, Daniel R
• Application Number:
  US16/017,084
• Publication Number:
  US 20180312472A1
• Time in Patent Office: 680 Days
• Field of Search: 5142664
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07D 239/94 Nitrogen atoms

Abstract

Disclosed are crystal forms K, E, F and G of the dimaleate of the compound as shown in formula I, and preparation methods and uses thereof. The crystal forms K, E, F and G have superior storage stability and solubility, so that they are more suitable for being used as the drug substance for drug product preparations.

Claims

1. A crystal form E of the dimaleate of the compound of Formula I,

2. The crystal form E according to claim 1, characterized in that the relative intensities of the characteristic peaks are:

7. A composition comprising the crystal form E of the dimaleate of the compound of Formula I according to claim 1.

10. A method for treating indications associated with EGFR and HER2 kinase function, the method comprising:

administering the crystal form E of the dimaleate of the compound of Formula I according to claim 1;

wherein the indication associated with EGFR and HER2 kinase function is selected from the group consisting of breast cancer, ovarian cancer, gastrointestinal cancer, esophageal cancer, lung cancer, head and neck squamous cell carcinoma, pancreatic cancer, epidermal squamous carcinoma, prostate cancer, glioma, nasopharyngeal cancer and combinations thereof.

3. A crystal form F of the dimaleate of the compound of Formula I,

4. The crystal form F according to claim 3, characterized in that the relative intensities of the characteristic peaks are:

8. A composition comprising the crystal form F of the dimaleate of the compound of Formula I according to claim 3.

11. A method for treating indications associated with EGFR and HER2 kinase function, the method comprising:

administering the crystal form F of the dimaleate of the compound of Formula I according to claim 3;

wherein the indication associated with EGFR and HER2 kinase function is selected from the group consisting of breast cancer, ovarian cancer, gastrointestinal cancer, esophageal cancer, lung cancer, head and neck squamous cell carcinoma, pancreatic cancer, epidermal squamous carcinoma, prostate cancer, glioma, nasopharyngeal cancer and combinations thereof.

5. A crystal form G of the dimaleate of the compound of Formula I,

6. The crystal form G according to claim 5, characterized in that the relative intensities of the characteristic peaks are:

9. A composition comprising the crystal form G of the dimaleate of the compound of Formula I according to claim 5.

12. A method for treating indications associated with EGFR and HER2 kinase function, the method comprising:

administering the crystal form G of the dimaleate of the compound of Formula I according to claim 5;

wherein the indication associated with EGFR and HER2 kinase function is selected from the group consisting of breast cancer, ovarian cancer, gastrointestinal cancer, esophageal cancer, lung cancer, head and neck squamous cell carcinoma, pancreatic cancer, epidermal squamous carcinoma, prostate cancer, glioma, nasopharyngeal cancer and combinations thereof.