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

Benzothiazole compounds and their use as medicine

A technology for benzothiazoles and compounds is applied in the field of benzothiazoles and their preparation, and can solve the problems of unresolved crystal structures and the like

Active Publication Date: 2018-07-17
SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY +1
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Domain II (amino acid sequence: 250-342) and domain III (amino acid sequence: 356-447) also play an important role in virus replication and assembly, but their specific crystal structures have not been resolved

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
  • Benzothiazole compounds and their use as medicine
  • Benzothiazole compounds and their use as medicine
  • Benzothiazole compounds and their use as medicine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0103] Example 1: Synthesis of 2-[6-(cyclopropylcarboxamido)-benzothiazole-2-carbamoyl]-pyrrole-1-acid benzyl ester

[0104] Step 1: Synthesis of 2-(6-nitrobenzothiazole-2-carbamoyl)-pyrrole-1-acid benzyl ester (III)

[0105] N-Benzyloxycarbonyl-L-proline (9.58g, 38.4mmol) and EDC.HCl (7.37g, 38.4mmol) were dissolved in dichloromethane and stirred at room temperature for 30min, then added 2- Amino-6-nitrobenzothiazole (5.00 g, 25.6 mmol) was added with a catalytic amount of DMAP (0.31 g, 2.54 mmol) and the reaction was continued to stir at room temperature overnight. After the reaction was completed, the solvent was evaporated to dryness and the sample was mixed in a dry method, and then purified by column chromatography (hexane:EtOAc=3:1) to obtain 10.05 g of a yellow solid with a yield of 92.03%.

[0106] 1 H NMRδ(300MHz, CDCl 3 ):11.33(brs,1H),8.71(s,1H),8.29(d,J=8.73Hz,1H),7.82(d,J=8.94Hz,1H),7.30-7.48(m,4H),7.00 -7.16(m,1H),5.17-5.32(m,2H),4.60-7.77(m,1H),3.43-3.67(m,...

Embodiment 2

[0116] Example 2: Synthesis of 2-[6-(1-naphthyl-formylamino)-benzothiazole-2-carbamoyl]-pyrrole-1-acid benzyl ester

[0117] According to the method of Example 1, step 3a, 1-naphthoic acid is used instead of cyclopropyl formic acid to obtain 2-[6-(1-naphthyl-carboxamido)-benzothiazole-2-carbamoyl]-pyrrole- Benzyl 1-acid, 85.8 mg of yellow solid, yield 61.77%.

[0118] 1 H NMRδ(300MHz,DMSO-d6):12.53(brs,1H),10.75(brs,1H),8.59(m,1H),8.21-8.23(m,1H),8.08(d,J=8.19Hz,1H ),8.00-8.03(m,1H),7.74-7.79(m,3H),7.58-7.64(m,3H),7.37-7.38(m,2H),7.03-7.19(m,3H),4.90-5.13 (m,2H),4.51-4.58(m,1H),3.52-3.54(m,2H),2.25-2.34(m,1H),1.85-1.92(m,3H).MS(ESI)m / z: 551.17(M+1).

Embodiment 3

[0119] Example 3: Synthesis of 2-[6-(4-fluorobenzamido)-benzothiazole-2-carbamoyl]-pyrrole-1-acid benzyl ester

[0120] According to the method of step 3b of Example 1, replace cyclopropylformyl chloride with p-fluorobenzoyl chloride to obtain 2-[6-(4-fluorobenzamido)-benzothiazole-2-carbamoyl]-pyrrole Benzyl-1-acid, 90.7 mg of light yellow solid, yield 69.34%.

[0121] 1 H NMRδ(300MHz, DMSO-d6):12.54(brs,1H),10.43(brs,1H),8.40-8.54(m,1H),8.06(t,J=6.03Hz,2H),7.68-7.83(m ,2H),7.35-7.40(m,5H),7.04-7.18(m,3H),4.90-5.13(m,2H),4.50-4.56(m,1H),3.56-3.58(m,2H),2.27 -2.29(m,1H),1.87-1.92(m,3H).MS(ESI)m / z:519.31(M+1).

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

PropertyMeasurementUnit
molecular weightaaaaaaaaaa
Login to View More

Abstract

The invention relates to the medical technical field, and provides benzothiazole compounds, and racemates and d-type or l-type isomers thereof, wherein the compounds have the structure represented by the formula (I). Pharmacological experiments indicate that the compounds have better inhibitory effect on HCV, act on a nonstructural protein NS5A target spot of the HCV, and have better in-vitro anti-HCV activity. The invention also provides a preparation method of the compounds, and an application thereof in preparation of anti-HCV inhibitors.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a class of benzothiazole compounds, a preparation method thereof, and an application as a medicine. Background technique [0002] Hepatitis C virus (HCV) infection seriously endangers human health and is one of the main causes of post-transfusion hepatitis. At present, ribavirin and pegylated interferon are mainly used in combination therapy clinically, but the effective genotypes are limited, the effect is not good, and it is easy to cause drug resistance. So far, there is no safe and effective vaccine that can prevent and completely suppress HCV. Although the listing of Boceprevir and Telaprevir is considered to have opened up a new era of HCV treatment, they are very expensive and still cannot completely cure HCV patients. [0003] HCV belongs to the genus Flavivirus, which is a single-stranded positive-sense RNA with 6 genotypes and more than 50 subtypes. The full length o...

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 Patents(China)
IPC IPC(8): C07D417/12C07D417/14A61K31/428A61K31/4439A61P31/14
Inventor 盛春泉袁正宏朱仕平张小楠张万年董国强缪震元姚建忠刘娜
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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