Aminoquinazoline Derivative And Use Thereof In Preparing Anti-Malignant Tumor Medicament

• US 20150065709A1
• Filed: 03/13/2013
• Published: 03/05/2015
• Est. Priority Date: 06/21/2011
• Status: Abandoned Application

• Current Assignee: Metabomics, Inc.
• Original Assignee: Metabomics, Inc.
• Inventors: Yin, Jianming, Tao, Junhua
• Application Number:
  US14/385,734
• Publication Number:
  US 20150065709A1
• Time in Patent Office: Days
• US Class Current: 544/284
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 239/94 Nitrogen atoms
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/14 containing three or more hetero rings

Abstract

The invention discloses a new amino-quinazoline derivative and its use in preparing drugs for preventing and/or treating malignancies. The amino-quinazoline derivative of the invention is an ideal, high effective, dual and irreversible EGFR and HER2 kinase inhibitor, and can treat or prevent various malignancy diseases, such as breast cancer, ovarian cancer, gastrointestinal cancer, oesophageal cancer, lung cancer, head and neck squamous cancer, pancreatic cancer, epidermis squamous cell cancer, prostatic cancer, neuroglioma and nasopharynx cancer.

Claims

1. A compound of the Formula (I), a pharmaceutically acceptable salt or hydrate thereof, a prodrug thereof, or a metabolite thereof produced in any type of metabolism,

2. The compound of the Formula (I), the pharmaceutically acceptable saltor hydrate thereof, the prodrug thereof, or the metabolite thereof produced in any type of metabolism as claimed in claim 1, wherein in the Formula (I), R₁ is selected from the group consisting of —

CHF₂, chlorinated ethyl and tetrahydrofuryl, and wherein R₂, R₃, n and A are defined as in claim 1.

3. The compound of the Formula (I), the pharmaceutically acceptable salt or hydrate thereof, the prodrug thereof, or the metabolite thereof produced in any type of metabolism as claimed in claim 2, wherein R₁ is —

CHF₂ or

4. The compound of the Formula (I), the pharmaceutically acceptable salt or hydrate thereof, the prodrug thereof, or the metabolite thereof produced in any type of metabolism as claimed in claim 1, wherein in the Formula (I), R₂ is Cl, R₃ is F;

and wherein R₁, n and A are defined as in claim 1.

5. The compound of the Formula (I), the pharmaceutically acceptable salt or hydrate thereof, the prodrug thereof, or the metabolite thereof produced in any type of metabolism as claimed in claim 1, wherein in the Formula (I), n is 0 or 1;

and wherein R₁, R₂, R₃ and A are defined as in claim 1.

6. The compound of the Formula (I), the pharmaceutically acceptable salt or hydrate thereof, the prodrug thereof, or the metabolite thereof produced in any type of metabolism as claimed in claim 1, wherein in the Formula (I), A is selected from the group consisting of —

N(CH₃)₂, —

N(CH₃)CH₂CH₃, —

N(CH₃)CH₂Ph, imidazolyl, pyridyl, unsubstituted and alkyl-substituted butyrolactam and valerolactam, and wherein R₁, R₂, R₃ and n are defined as in claim 1.

7. The compound of the Formula (I), the pharmaceutically acceptable salt or hydrate thereof, the prodrug thereof, or the metabolite thereof produced in any type of metabolism as claimed in claim 6, wherein A is

8. The compound of the Formula (I), the pharmaceutically acceptable salt or hydrate thereof, the prodrug thereof, or the metabolite thereof produced in any type of metabolism as claimed in claim 1, wherein the compound is selected from the compounds respectively having the following formulas:

11. A method of preventing at least one indication associated with EGFR and HER2 kinase functions in a subject in need thereof, comprising administering an effective amount of the Formula (I), the pharmaceutically acceptable salt or hydrate thereof, the prodrug thereof, or the metabolite thereof produced in any type of metabolism as claimed in claim 1.

12. The method of claim 11, wherein the indication associated with EGFR and HER2 kinase functions is breast cancer, ovarian cancer, gastrointestinal cancer, oesophageal cancer, lung cancer, head and neck squamous cancer, pancreatic cancer, epidermis squamous cancer, prostatic cancer, neuroglioma, or nasopharynx cancer.

13. A method of treating at least one indication associated with EGFR and HER2 kinase functions in a subject in need thereof, comprising administering an effective amount of a the Formula (I), the pharmaceutically acceptable salt or hydrate thereof, the prodrug thereof, or the metabolite thereof produced in any type of metabolism as claimed in claim 1.

14. The method of claim 13, wherein the indication associated with EGFR and HER2 kinase functions is breast cancer, ovarian cancer, gastrointestinal cancer, oesophageal cancer, lung cancer, head and neck squamous cancer, pancreatic cancer, epidermis squamous cancer, prostatic cancer, neuroglioma, or nasopharynx cancer.

9. (canceled)

10. (canceled)