IMIDAZOPYRIDINAMINE PHENYL DERIVATIVE AND USE THEREOF

• US 20190211023A1
• Filed: 06/29/2017
• Published: 07/11/2019
• Est. Priority Date: 06/30/2016
• Status: Active Grant

• Current Assignee: Hangzhou Bangshun Pharmaceutical Company Limited
• Original Assignee: Hangzhou Sanyintai Pharmaceutical Technology Co., Ltd.
• Inventors: YIN, Jianming, LV, Yubin, LI, Bangliang
• Granted Patent: US 10,640,512 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/4985 Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

Imidazopyrazinamine phenyl derivatives, pharmaceutically acceptable salts and hydrates thereof, or metabolites thereof formed by any form of metabolism, and uses thereof in the preparation of medicaments for preventing and/or treating indications/diseases associated with BTK functions are disclosed. The disclosed imidazopyrazinamine phenyl derivatives are ideal high-efficient BTK inhibitors for treating or preventing diseases such as rheumatoid arthritis, B cell lymphoma, leukemia, multiple myeloma, allergies, asthma, multiple sclerosis, type I diabetes and systemic lupus erythematosus.

Claims

1. An imidazopyrazinamine phenyl derivative having a structure represented by general formula (I), a pharmaceutically acceptable salt and hydrate thereof, or a metabolite thereof formed by any form of metabolism,

2. The imidazopyrazinamine phenyl derivative according to claim 1, a pharmaceutically acceptable salt and hydrate thereof, or a metabolite thereof formed by any form of metabolism, wherein R₁ is a benzene ring, a six-membered heteroaromatic ring containing 1 or 2 nitrogens, which is optionally substituted with 0-2 C1-C4 alkyls.

3. The imidazopyrazinamine phenyl derivative according to claim 1, a pharmaceutically acceptable salt and hydrate thereof, or a metabolite thereof formed by any form of metabolism, wherein R₂ is H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl.

4. The imidazopyrazinamine phenyl derivative according to claim 1, a pharmaceutically acceptable salt and hydrate thereof, or a metabolite thereof formed by any form of metabolism, wherein R₃ is

5. The imidazopyrazinamine phenyl derivative according to claim 1, a pharmaceutically acceptable salt and hydrate thereof, or a metabolite thereof formed by any form of metabolism, wherein R₅ is H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl.

6. The imidazopyrazinamine phenyl derivative according to claim 1, a pharmaceutically acceptable salt and hydrate thereof, or a metabolite thereof formed by any form of metabolism, wherein the imidazopyrazinamine phenyl derivative is one of the compounds represented by the following structural formulas:

13. A method for preventing and/or treating indications/diseases associated with BTK functions, the method comprising administering the imidazopyrazinamine phenyl derivative having a structure represented by general formula (I) according to claim 1, a pharmaceutically acceptable salt and hydrate thereof, or a metabolite thereof formed by any form of metabolism.

14. The method according to claim 13, wherein the indications/diseases associated with BTK functions can be rheumatoid arthritis, B cell lymphoma, leukemia, multiple myeloma, allergies, asthma, multiple sclerosis, type I diabetes or systemic lupus erythematosus.

15. Intermediate, for the preparation of the imidazopyrazinamine phenyl derivative having general formula (I) according to claim 1, a pharmaceutically acceptable salt and hydrate thereof, or a metabolite thereof formed by any form of metabolism, wherein the general structural formula of the intermediate is:

7-12. -12. (canceled)