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Inhibitor salt or crystal form containing di-fused ring derivative and preparation method and application of inhibitor salt or crystal form

A crystal form and diazabicyclo technology, applied in the field of drug synthesis, can solve the problems of large clinical needs and no specific targeted drugs for RET targets

Pending Publication Date: 2022-05-13
SHANGHAI HANSOH BIOMEDICAL +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] There is currently no specific targeted drug for the RET target, and there is a large clinical demand

Method used

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  • Inhibitor salt or crystal form containing di-fused ring derivative and preparation method and application of inhibitor salt or crystal form

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Embodiment Construction

[0200]Unless stated to the contrary, the terms used in the specification and claims have the following meanings.

[0201] The term "alkyl" refers to a saturated aliphatic hydrocarbon group which is a straight or branched chain group containing 1 to 20 carbon atoms, preferably an alkyl group containing 1 to 8 carbon atoms, more preferably 1 to 6 carbon atoms An alkyl group, most preferably an alkyl group of 1 to 3 carbon atoms. Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1 ,2-Dimethylpropyl, 2,2-Dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2- Methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3 -Dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, n-heptyl, 2 -Methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 2,3-dimethylpentyl, 2,4-dimethylpentyl, 2,2-dim...

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Abstract

The invention relates to a salt containing a bicyclic derivative inhibitor, and a crystal form, a preparation method and application thereof. Specifically, the invention relates to a preparation method of a compound 6-(((R)-2-hydroxy-2-methylbutyl-3-alkyn-1-yl) oxy)-4-(6-(6-((6-methoxypyridine-3-yl) methyl)-3, 6-diazabicyclo [3.1. 1] heptane-3-yl) pyridine-3-yl) pyrazolo [1, 2-a] pyridine. The invention relates to a salt of [1, 5-a] pyridine-3-formonitrile, a crystal form thereof, a preparation method thereof, a pharmaceutical composition containing a therapeutically effective amount of the salt of the compound or the crystal form thereof, and application of the salt or the crystal form thereof as an RET inhibitor in treatment of cancers, inflammation, chronic liver diseases, diabetes, cardiovascular diseases, AIDS and other related diseases.

Description

technical field [0001] The invention belongs to the field of drug synthesis, and in particular relates to an inhibitor salt or crystal form containing a biscyclic derivative and a preparation method and application thereof. Background technique [0002] RET (rearranged during transfection) protein is encoded by the proto-oncogene RET located on chromosome 10. It is a receptor tyrosine kinase and consists of an extracellular region, a transmembrane region and an intracellular kinase region. RET ligands are glial cell-derived neurotrophic factor (GDNF) family ligands (GFLs) such as GDNF, neurturin (NRTN), artemin (ARTN), persephin (PSPN), activation of receptors also requires co-receptor GFRα The joint function of the family, GFLs and GFRα form a dimer, bind RET and recruit it to the cholesterol-rich membrane region, RET protein dimerization and autophosphorylation, thereby activating the downstream RAS-MAPK, PI3K-AKT , PKC and other signaling pathways. RET plays an importan...

Claims

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Application Information

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IPC IPC(8): C07D519/00A61P35/00A61K31/444
CPCC07D519/00A61P35/00C07B2200/13C07B2200/07
Inventor 董华呙临松
Owner SHANGHAI HANSOH BIOMEDICAL
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