INDOLE-FORMAMIDE DERIVATIVE, PREPARATION METHOD THEREFOR AND USE THEREOF IN MEDICINE

• US 20200131123A1
• Filed: 07/05/2018
• Published: 04/30/2020
• Est. Priority Date: 07/06/2017
• Status: Active Application

• Current Assignee: Jiangsu Hengrui Medicine Company Limited, Shanghai Hengrui Pharmaceutical Co., Ltd. (Jiangsu Hengrui Pharmaceuticals Co., Ltd.)
• Original Assignee: Jiangsu Hengrui Medicine Company Limited, Shanghai Hengrui Pharmaceutical Co., Ltd. (Jiangsu Hengrui Pharmaceuticals Co., Ltd.)
• Inventors: LIU, Dong, LU, Biao, QIAN, Wenjian, DONG, Huaide, LIU, Suxing, ZHANG, Rumin, HE, Feng, TAO, Weikang
• Application Number:
  US16/627,590
• Publication Number:
  US 20200131123A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 209/18 Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 209/42 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 403/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 413/06 linked by a carbon chain containing only aliphatic carbon atoms

Abstract

A solid dispersion, a method for preparing same, and a solid preparation comprising the solid dispersion. The solid dispersion contains (R)-4-amino-1-(1-(but-2-ynylacyl)pyrrolidin-3-yl)-3-(4-(2,6-difluorophenoxy)phenyl)-1,6-dihydro-7H-pyrrolo[2,3-d]pyridazine-7-one or a pharmaceutically acceptable salt thereof, and a carrier material. The carrier material is selected from hydroxypropyl methylcellulose acetate succinate and hydroxypropyl methylcellulose phthalate.

Claims

1. A compound of formula (I):

2. The compound of formula (I) according to claim 1, wherein the compound is a compound of formula (IA):

3. The compound of formula (I) according to claim 1, wherein the compound is a compound of formula (II):

4. The compound of formula (I) according to claim 1, or a tautomer, mesomer, racemate, enantiomer, diastereomer thereof, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein ring A is selected from the group consisting of phenyl, pyridyl, imidazolyl, pyrazolyl and morpholinyl.

5. The compound of formula (I) according to claim 1, wherein the compound is a compound of formula (III):

6. The compound of formula (I) according to claim 1, wherein the compound is a compound of formula (IV):

7. The compound of formula (I) according to claim 1, or a tautomer, mesomer, racemate, enantiomer, diastereomer thereof, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein R¹ is selected from the group consisting of hydrogen, halogen and alkyl.

8. The compound of formula (I) according to claim 1, or a tautomer, mesomer, racemate, enantiomer, diastereomer thereof, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein R⁵ is selected from the group consisting of alkyl, NR¹⁰R¹¹ and cycloalkyl, wherein the alkyl and cycloalkyl are each independently optionally substituted by one or more substituents selected from the group consisting of hydroxy, halogen, alkyl, amino, cycloalkyl and heterocyclyl;

and R¹⁰ and R¹¹ are as defined in claim 1.

9. The compound of formula (I) according to claim 1, or a tautomer, mesomer, racemate, enantiomer, diastereomer thereof, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein R⁶ is hydrogen or halogen.

10. The compound of formula (I) according to claim 1, or a tautomer, mesomer, racemate, enantiomer, diastereomer thereof, or mixture thereof, or a pharmaceutically acceptable salt thereof, wherein R⁷ is selected from the group consisting of alkyl, cycloalkyl and haloalkyl.

12. A pharmaceutical composition, comprising a therapeutically effective amount of the compound of formula (I) according to claim 1, or a tautomer, mesomer racemate, enantiomer, diastereomer thereof, or mixture thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, diluents or excipients.

13. The pharmaceutical composition according to claim 12, further comprising an anti-PD-1 antibody.

17. A method of treating a tumor or cancer, comprising administrating to a patient in need thereof a therapeutically effective amount of the compound of formula (I) of claim 1, or a tautomer, mesomer, racemate, enantiomer, diastereomer thereof, or mixture thereof, or a pharmaceutically acceptable salt thereof.

18. A method of treating a tumor or cancer, comprising administrating to a patient in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 13.

11. A compound selected from the group consisting of:

19. A pharmaceutical composition, comprising a therapeutically effective amount of the compound according to claim 11, and one or more pharmaceutically acceptable carriers, diluents or excipients.

20. The pharmaceutical composition according to claim 19, further comprising an anti-PD-1 antibody.

21. A method of treating a tumor or cancer, comprising administrating to a patient in need thereof a therapeutically effective amount of the compound of claim 11, or a tautomer, mesomer, racemate, enantiomer, diastereomer thereof, or mixture thereof, or a pharmaceutically acceptable salt thereof.

22. A method of treating a tumor or cancer, comprising administrating to a patient in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 20.

14-16. -16. (canceled)