Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Isopropylpiperazine thiophene bicyclic nitrile compound as well as preparation method and application thereof

A compound, dibromide technology, used in organic chemistry, drug combinations, antipyretics, etc.

Inactive Publication Date: 2018-06-08
FOSHAN HANFANG CHINESE MEDICINE HOSPITAL CO LTD
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The precise physiological role of this abundant enzyme has not been fully determined, but it appears that SSAO and its reaction products may have several functions in cellular signal transduction and regulation

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
  • Isopropylpiperazine thiophene bicyclic nitrile compound as well as preparation method and application thereof
  • Isopropylpiperazine thiophene bicyclic nitrile compound as well as preparation method and application thereof
  • Isopropylpiperazine thiophene bicyclic nitrile compound as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] The synthesis of embodiment 1 lead compound I-1

[0022]

[0023] Step 1. Synthesis of compound IV-1

[0024] Compound II-1 (2.42g, 10mmol), Compound III (1.08g, 10mmol), Pd(OAc) 2 (0.22g, 1mmol), BINAP (2,2'-bisdiphenylphosphino-1,1'-binaphthyl, 0.62g, 1mmol) and t-BuOK (2.24g, 20mmol) were added to 50mL dry 1 , 2-dimethoxyethane (DME), the reaction mixture was stirred overnight under nitrogen atmosphere, TLC detection found that the reaction was complete.

[0025] The reaction mixture was carefully poured into 200mL ice water, stirred, and washed with 50mL×3CH 2 Cl 2 After extraction, the extract phases were combined, washed successively with 1% dilute hydrochloric acid and brine, and dried over anhydrous sodium sulfate. The desiccant was removed by suction filtration, the filtrate was evaporated to dryness on a rotary evaporator, and the residue was purified by silica gel column chromatography to obtain compound IV-I, 1.88 g (yield 70%). ESI-MS, m / z=270 ([M+...

Embodiment 2

[0029] The synthesis of embodiment 2 compound 1-2

[0030]

[0031] Step 1. Synthesis of compound IV-2

[0032] Compound II-2 (2.67g, 10mmol), Compound III (1.08g, 10mmol), Pd(OAc) 2(0.22g, 1mmol), BINAP (2,2'-bisdiphenylphosphino-1,1'-binaphthyl, 0.62g, 1mmol) and t-BuOK (2.24g, 20mmol) were added to 50mL dry 1 , 2-dimethoxyethane (DME), the reaction mixture was stirred overnight under nitrogen atmosphere, TLC detection found that the reaction was complete.

[0033] The reaction mixture was carefully poured into 200mL ice water, stirred, and washed with 50mL×3CH 2 Cl 2 After extraction, the extract phases were combined, washed successively with 1% dilute hydrochloric acid and brine, and dried over anhydrous sodium sulfate. The desiccant was removed by suction filtration, the filtrate was evaporated to dryness on a rotary evaporator, and the residue was purified by silica gel column chromatography to obtain compound IV-2, ESI-MS, m / z=295 ([M+H] + ).

[0034] Step 2....

Embodiment 3

[0037] Example 3 compound in vitro inhibition of SSAO analysis

[0038] All preliminary assays were performed at room temperature using purified recombinantly expressed human SSAO. Enzymes were prepared essentially as described in Ohman et al. (Protein Expression and Purification, 2006, 46, 321-331). In addition, secondary and selectivity assays were performed using SSAO prepared from various tissues or purified rat recombinant SSAO. Enzyme activity was determined by using hydrogen peroxide generation in a horseradish peroxidase (HRP) coupled reaction using benzylamine as a substrate. Briefly, test compounds were dissolved in dimethyl sulfoxide (DMSO) to a concentration of 10 mM. Dose-response measurements were determined by serial dilutions of 1:10 in DMSO to generate 7-point curves or by serial dilutions of 1:3 in DMSO to generate 11-point curves. The highest concentration was adjusted according to the potency of the compound and then diluted in reaction buffer to give ...

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 present invention relates to the field of SSAO (semicarbazide-sensitive amine oxidase) inhibitors, and in particular relates to a bicyclic nitrile compound containing isopropylpiperazine thiopheneas well as a preparation method of the compound and an application of the compound in preparation of a medicine for treating diseases such as inflammatory diseases, immune diseases and tumors.

Description

technical field [0001] The present invention relates to the field of SSAO inhibitors. Specifically, the present invention relates to an SSAO inhibitor of a bicyclic nitrile compound containing isopropylpiperazinethiophene, which has a therapeutic effect on inhibiting SSAO, its preparation method, and its use in pharmacy. Background technique [0002] Semicarbazide-sensitive amine oxidase (SSAO) activity is produced by vascular adhesion protein-1 (Vascular Adhesinon Protein-1, VAP-1) or copper-containing amine oxidase (AmoneOxidase, Copper Containing 3, AOC3 ), which belongs to the family of copper-containing amine oxidases (EC.1.4.3.6). Therefore, inhibitors of SSAO enzymes can also regulate the biological functions of VAP-1 protein. Members of this enzyme family are sensitive to inhibition by semicarbazides and use copper ions and the protein-derived hydroxydopaquinine (TPQ) cofactor for the oxidation of primary amines to aldehydes, hydrogen peroxide, and ammonia Deamina...

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
IPC IPC(8): C07D409/04A61P29/00A61P37/02A61P35/00
CPCC07D409/04
Inventor 朱斌
Owner FOSHAN HANFANG CHINESE MEDICINE HOSPITAL CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com