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

Derivatives and methods of treating hepatitis B infections

A compound and alkyl technology, applied in the field of derivatives and methods for treating hepatitis B infection, can solve the problems of inability to provide cure, difficult complete inhibition, low cure rate and the like

Inactive Publication Date: 2018-01-02
NOVIRA THERAPEUTICS
View PDF1 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Despite the availability of preventive HBV vaccines, the burden of chronic HBV infection remains a major and unaddressed worldwide medical problem due to suboptimal treatment options and persistent new infection rates in large parts of the developing world
Current treatments offer no cure and are limited to only two classes of agents (interferon alpha and nucleoside analogs / inhibitors of viral polymerase); drug tolerance, low efficacy, and resistance issues limit their impact
The low cure rate of HBV is due at least in part to the fact that complete suppression of viral production is difficult to achieve with a single antiviral agent

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
  • Derivatives and methods of treating hepatitis B infections
  • Derivatives and methods of treating hepatitis B infections
  • Derivatives and methods of treating hepatitis B infections

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0317] Preparation of the optically active form is accomplished in any suitable manner, including, by way of non-limiting examples, resolution of the racemic form by recrystallization techniques, synthesis from optically active starting materials, chiral synthesis, or use of a chiral stationary phase Perform chromatographic separation. In one embodiment, mixtures of one or more isomers are used as therapeutic compounds described herein. In another embodiment, the compounds described herein contain one or more chiral centers. These compounds are prepared by any means including stereoselective synthesis, enantioselective synthesis and / or separation of enantiomeric and / or diastereomeric mixtures. Resolution of compounds and isomers thereof is achieved by any means including, by way of non-limiting examples, chemical methods, enzymatic methods, fractional crystallization, distillation and chromatography.

[0318] In one embodiment, the compounds of the invention may exist as tau...

Embodiment 1

[0394] Example 1: Preparation of Compounds 010 and 059

[0395]

[0396] Step 1: Preparation of compound 3

[0397] at 30°C and N 2 3-Phenyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine (1.00 g, 4.24 mmol, 1.00 equiv) and 2-phenoxyacetic acid ( A mixture of 645.50 mg, 4.24 mmol, 1.00 equiv) in DCM (40 mL) was added in one portion with HATU (1.93 g, 5.09 mmol, 1.20 equiv) and DIPEA (1.37 g, 10.60 mmol, 2.50 equiv). The mixture was stirred at 30°C for 12 hours. LCMS showed the reaction was complete. The mixture was poured into water (50 mL) and stirred for 2 min. The aqueous phase was extracted with DCM (20 mL*2). The combined organic phases were washed with saturated brine (20mL*2), washed with anhydrous Na 2 SO 4Dry, filter and concentrate in vacuo. The residue was purified by silica gel chromatography (petroleum ether / ethyl acetate=3 / 1) to give 2-phenoxy-1-(3-phenyl-1,4,6,7-tetrahydro as a yellow solid Pyrazolo[4,3-c]pyridin-5-yl)ethanone (1.30 g, 3.90 mmol, ...

Embodiment 2

[0400] Embodiment 2: the preparation of compound 011 and 060

[0401]

[0402] at 0°C and N 2 , to 2-phenoxy-1-(3-phenyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl)ethanone (150.00mg, 449.94 umol, 1.00 equiv) in DMF (10 mL) was added NaH (36.00 mg, 899.88 umol, 2.00 equiv) in one portion. The mixture was stirred at 0°C for 0.5 hours, then ethyl iodide (210.53 mg, 1.35 mmol, 3.00 equiv) was added to the mixture at 0°C. The mixture was heated to 30°C and stirred for 12 hours. LCMS showed the reaction was complete. The mixture was quenched with water (5 mL) and stirred for 5 min. The aqueous phase was extracted with ethyl acetate (15 mL*2). The combined organic phases were washed with saturated brine (15mL*2), washed with anhydrous Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue was purified by preparative HPLC (FA) to give 1-(1-ethyl-3-phenyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine as a white solid -5-yl)-2-phenoxy-ethanone (71.20mg, 196.99umol, 43.78...

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

Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject.

Description

[0001] Related Patent Applications [0002] This patent application claims priority to US Provisional Application 62 / 097,835, filed December 30, 2014, and US Provisional Application 62 / 163,150, filed May 18, 2015. The entire contents of these provisional applications are incorporated herein by reference. Background technique [0003] Chronic hepatitis B virus (HBV) is a major global health problem, affecting more than 5% of the world's population (more than 350 million people worldwide and 1.25 million individuals in the United States). [0004] Despite the availability of preventive HBV vaccines, the burden of chronic HBV infection remains a major and unaddressed worldwide medical problem due to suboptimal treatment options and persistent rates of new infections in large parts of the developing world. Current treatments offer no cure and are limited to only two classes of agents (interferon alpha and nucleoside analogs / inhibitors of viral polymerase); drug tolerance, low ef...

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): C07D471/04A61K31/437A61P31/20
CPCC12N2730/10111A61K31/4545A61P31/12C07D471/04A61K38/212A61K31/437A61K31/5377A61K45/06A61K2300/00A61K31/501A61K39/292C12N7/00C12N2730/10134A61K31/4375C12N2730/10171
Inventor G.D.哈特曼S.库杜克
Owner NOVIRA THERAPEUTICS
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