Alkyne derivative, preparation method for same, and uses thereof

Patent metadata

Field	Value
Publication number	US-12447151-B2
Application number	US-202017625103-A
Country	US
Kind code	B2
Filing date	Jul 6, 2020
Priority date	Jul 8, 2019
Publication date	Oct 21, 2025
Grant date	Oct 21, 2025

Abstract

The present invention relates to an alkyne derivative, a preparation method for same, and applications thereof in medicine. Specifically, the present invention relates to the alkyne derivative as represented by formula (I), the preparation method for same, a pharmaceutically acceptable salt thereof, and uses of them as a therapeutic agent, specifically as a phosphoinositide 3-kinase γ (PI3Kγ) inhibitor, where the definitions of the substituents in formula (I) are identical to the definitions in the description.

First claim

The invention claimed is:

1. The compound of formula (I) or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof:

wherein:
X is selected from CH or N;
R 1 is selected from cycloalkyl or heterocyclyl, wherein said cycloalkyl or heterocyclyl is optionally further substituted by one or more substituents selected from hydroxyl, halogen, nitro, cyano, alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl or —NR 5 R 6 ;
R 2 and R 3 are each independently selected from hydrogen atom, alkyl, alkoxy, cyano or halogen, wherein the alkyl or alkoxy is optionally further substituted with one or more halogens;
R 4 is the same or different, each independently selected from hydrogen atom, alkyl, alkoxy, cyano or halogen, wherein the alkyl or alkoxy is optionally further substituted with one or more halogens;
R 5 and R 6 are each independently selected from hydrogen atom, alkyl or cycloalkyl, wherein the alkyl or cycloalkyl is optionally further substituted by one or more substituents selected from hydroxyl, halogen, cyano, alkyl, alkoxy, cycloalkyl or heterocyclyl; and
m is 0, 1, 2, 3, 4, or 5.

2. The compound or the stereoisomer, tautomer, or pharmaceutically acceptable salt thereof according to claim 1 , wherein: R 1 is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or oxetanyl.

3. The compound or the stereoisomer, tautomer, or pharmaceutically acceptable salt thereof according to claim 1 , wherein: R 1 is cyclopropyl or oxetanyl.

4. The compound or the stereoisomer, tautomer, or pharmaceutically acceptable salt thereof according to claim 1 , wherein: R 2 and R 3 are each independently selected from hydrogen atom or halogen.

5. The compound or the stereoisomer, tautomer, or pharmaceutically acceptable salt thereof according to claim 1 , wherein: R 4 is the same or different, each independently selected from hydrogen atom, alkyl or halogen, and m is 0, 1, 2 or 3.

6. The compound or the stereoisomer, tautomer, or pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is selected from:

7. A pharmaceutical composition comprising an effective dose of the compound or the stereoisomer, tautomer, or pharmaceutically acceptable salt thereof according to claim 1 , and pharmaceutically acceptable carriers, excipients or combinations thereof.

8. The compound or the stereoisomer, tautomer, or pharmaceutically acceptable salt thereof according to claim 1 , wherein: R 2 and R 3 are both fluorine.

9. The compound or the stereoisomer, tautomer, or pharmaceutically acceptable salt thereof according to claim 1 , wherein R 4 is hydrogen.

Assignees

• Zhejiang Hisun Pharm Co Ltd
• Shanghai Aryl Pharmtech Co Ltd
• His Pharmaceutical Co Ltd

Inventors

• Lv Hejun
• Ma Yutao
• Qiu Haibo
• Zhao Wenwen
• Hu taishan
• Chen Lei

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P35/02

  specific for leukemia · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P11/06

  Antiasthmatics · CPC title