Heterocyclic compound and application thereof in medicine

A technology of compounds, mixtures of isomers, applied in the field of medicine

Inactive Publication Date: 2022-08-02
KIND PHARMA
View PDF10 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Although SERDs have shown compelling promise in the treatment of ER-related diseases such as breast cancer, so far, no small-molecule drugs that can be administered orally for SERDs have entered the market.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Heterocyclic compound and application thereof in medicine
  • Heterocyclic compound and application thereof in medicine
  • Heterocyclic compound and application thereof in medicine

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0178] Preparation of intermediate compounds

[0179] Preparation of Intermediate I-100':

[0180]

[0181] 1-(2,3-Difluoropropyl)azetidine-3-amine ( I-100’-1 )

[0182]

[0183] first step

[0184] 2-benzyloxymethyloxirane ( I-100’-1-a )

[0185]

[0186] NaOH (3.7 g), tetra-n-butylammonium iodide TBAI (3.43 g) and DMF (150 mL) were added to the reaction flask, cooled in an ice-water bath, and then oxiran-2-ylmethanol (CAS: 556- 52-5; 6.85 g) was dropped into the reaction flask and stirred for 2 hours; then benzyl bromide BnBr (17.3 g) was slowly added dropwise; after the addition, the reaction was kept at room temperature overnight. Then, water was added to quench the reaction and extracted with ethyl acetate; the ethyl acetate layer was collected, washed twice with dilute aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated; the residue was purified by silica gel column chromatography to obtain oily product, I-...

Embodiment 1

[0261] 1-(3-Fluoropropyl)-N-(4-((6R,7S)-7-isobutyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h]isoquinolin-6-yl)phenyl)azetidine-3-amine ( 1 )

[0262]

[0263] first step

[0264] (2S)-2-(((1H-Indazol-4-yl)methyl)(methyl)amino)-1-(4-bromophenyl)-4-methylpentan-1-ol ( 1a )

[0265]

[0266] compound I-60-1 (839 mg), 4-(chloromethyl)-1H-indazole (ADV947321888 from Advanced ChemBlocks Inc., 739 mg), potassium carbonate (1.8 g) and sodium iodide (39 mg) were mixed at room temperature in no water in DMF. The reaction solution was stirred at room temperature overnight. Then, ethyl acetate and water were added for extraction; the organic phase was separated, and the organic phase was washed twice with dilute aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated; the residue was purified by silica gel column chromatography to obtain a yellow solid product 1a (950 mg). 1 H NMR (500 MHz, DMSO-d6) δ (ppm): 13.00 (1H, s), 8.07 (...

Embodiment 2

[0288] N-(3,5-Difluoro-4-((6S,7S)-7-isobutyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo[3,4 -h]isoquinolin-6-yl)phenyl)-1-(3-fluoropropyl)azetidine-3-amine ( 2 )

[0289]

[0290] first step

[0291] (2S)-2-(((1H-Indazol-4-yl)methyl)(methyl)amino)-1-(4-chloro-2,6-difluorophenyl)-4-methylpentan -1-ol ( 2a )

[0292]

[0293] compound I-60-2 (1130 mg), 4-(chloromethyl)-1H-indazole (ADV947321888 from Advanced ChemBlocks Inc., 630 mg), potassium carbonate (2.5 g) and sodium iodide (54 mg) were mixed at room temperature in no water in DMF. The reaction solution was stirred at room temperature overnight. Then, ethyl acetate and water were added for extraction; the organic phase was separated, and the organic phase was washed twice with dilute aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated; the residue was purified by silica gel column chromatography to obtain a yellow solid product 2a (1660 mg). 1 H NMR (500MHz, dmso-d6) ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention relates to a heterocyclic compound and application thereof in medicine. Specifically, the invention discloses a heterocyclic compound as shown in a general formula I, or an isotope labeled compound thereof, or an optical isomer, a geometric isomer, a tautomer or an isomer mixture thereof, or a pharmaceutically acceptable salt thereof, or a prodrug thereof. The invention also relates to application of the compounds in medicine.

Description

[0001] This application is a divisional application of an invention patent application with an application date of November 14, 2018, an application number of 201811354547.6, and the invention name of "heterocyclic compounds and their application in medicine". technical field [0002] The invention belongs to the field of medicine, and particularly relates to a compound related to the treatment of estrogen receptor-related diseases (such as breast cancer, etc.) and its preparation and application in medicine. Background technique [0003] Estrogen (estrogen), including estrone (estrone), estradiol (estradiol), etc., is mainly secreted by the ovary, a small amount by the liver, adrenal cortex and breast secretion. As the main sex hormone of female animals, estrogen promotes the maturation of female accessory sex organs and the appearance of secondary sexual characteristics, and maintains normal sexual desire and reproductive function. Its role is mainly through diffusion into...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C07D471/04A61K31/4745A61P35/00A61P15/00A61P25/28A61P9/00A61P19/10A61P37/06A61P5/50A61P3/04
CPCC07D471/04A61P35/00A61P15/00A61P25/28A61P9/00A61P19/10A61P37/06A61P5/50A61P3/04A61K31/4738A61K31/4745
Inventor 刘栋
Owner KIND PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap