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

Novel anti-infectives

A compound, alkyl technology, applied in the field of hepatitis C virus inhibitors, can solve the problem of weakened response in genotype 1 patients

Inactive Publication Date: 2004-10-06
SMITHKLINE BECKMAN CORP
View PDF0 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, side effects associated with combination therapy and diminished response in patients with genotype 1 suggest opportunities for improvement in the management of this disease

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
  • Novel anti-infectives
  • Novel anti-infectives
  • Novel anti-infectives

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0143] Alternative methods for the preparation of N-alkylated 1H-benzo[d][1,3]oxazine-2,4-diones (d) are shown in Scheme 5 and Scheme 6.

[0144] Option 5

[0145]

[0146] Conditions: i.W-CHO, NaBH 4 .THF; ii. Triphosgene, THF

[0147] One of the alternative methods for the preparation of N-alkylated 1H-benzo[d][1,3]oxazine-2,4-diones (d) is shown in Scheme 5, involving the reductive amination conditions 2-Aminobenzoic acid (a) is treated with the appropriate aldehyde ( W-CHO) treats 2-aminobenzoic acid to generate N-alkylated 2-aminobenzoic acid (r). Treatment of the N-alkylated 2-aminobenzoic acid (r) with phosgene or a phosgene equivalent such as triphosgene or ethyl chloroformate in a suitable solvent such as tetrahydrofuran as described above affords the N-alkylated 1H-Benzo[d][1,3]oxazine-2,4-dione (d).

[0148] Option 6

[0149]

[0150] Condition: i.W-NH 2 , 6mol% CuBr 2 , K 2 CO 3 , THF, 63°C; ii. Triphosgene, THF

[0151] Scheme 6 illustrates an...

test approach 1

[0157] Method for detecting positive strand replicon HCV-RNA in replicon cells

[0158] at 37°C and 5% CO 2 The replicon cells in DMEM (Dulbecco's Minimal Essential Medium) were mixed at 3×10 per well 3 The cells were plated in 96-well plates in DMEM containing 10% FCS (fetal calf serum), 1% NEAA (non-essential amino acids) and 1 mg / ml Geneticin (G418 neomycin). After allowing the cells to attach for 4 hours, 1 μl of the candidate antiviral agent solution was added to the medium (n=8 wells / dilution). Briefly, eleven 2.5-fold serial dilutions of test compounds from 1 mM stocks in DMSO (dimethyl sulfoxide) were prepared at final concentrations ranging from 10000 to 1.0 nM. Plates were incubated for 40 hours until reaching 80% confluency. After the medium was removed, 150 μl Buffer RLT (Qiagen, Valencia, California, US) was added to each well, and the RNA was purified according to the manufacturer’s recommendation (Qiagen RNAeasy), and 45 μl of dH 2 Dilute twice in O. Add ap...

test approach 2

[0160] Method for detecting negative strand replicon HCV-RNA in replicon cells

[0161] For strand-specific detection, perform a reverse transcription (RT) reaction using primers containing HCV RNA (or a replicon RNA sequence such as the neomycin gene) and an 18-base tag at the 5′ end of an unrelated sequence , 5'ACATGCGCGGCATCTAGACCGGCTACCTGCCCATTC3' (SEQ ID NO 4). RT reaction was carried out with Thermoscript-RT-PCR system (Invitrogen) according to the instruction manual, about 9 μl of RNA was harvested from the cells, and it was incubated with 1 μl of primer (10 μM) at 60° C. for 1 hour at RT. Afterwards, 2 μl of the cDNA product containing the 5′ tag was amplified for TaqMan quantification using 48 μl of TaqMan Universal Master Mix (Applied Biosystems) and the following primers: neo-forward tag: 5′ACA TGC GCG GCA TCT AGA 3' (SEQ ID NO 3); neo reverse: 5' CCAGATCATCCTGATCGACAAG 3' (SEQ ID NO 6); neo probe: 5' FAM-ACA TCG CAT CGA GCG AGC ACG TAC-TAMRA 3' (SEQ ID NO 3). The...

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

Compounds useful as HCV anti-infectives having the formula: wherein the formula variables are as defined herein, are disclosed. Also disclosed are methods of making and using the same.

Description

technical field [0001] The present invention relates to compounds that inhibit RNA-containing viruses, and methods of making and using the same. In particular, the present invention relates to inhibitors of hepatitis C virus (HCV). Background technique [0002] In the United States, an estimated 4.5 million Americans are chronically infected with HCV. Although only 30% of acute infections are symptomatic, more than 85% of those infected develop chronic, long-lasting infections. The estimated cost of treating HCV infection in the United States in 1997 was $5.46 billion. Worldwide, more than 200 million people are estimated to be living with chronic HCV infection. HCV infection is responsible for 40-60% of all chronic liver diseases and 30% of all liver transplants. According to CDC estimates, by 2010, the number of deaths caused by HCV will increase to at least 38,000 people per year. [0003] Due to the high variability of viral surface antigens, the presence of multipl...

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): A61K31/5415A61K31/7088A61K31/7105A61K38/00A61K38/16A61K38/21A61K39/00A61K45/00A61K48/00A61P1/16A61P29/00A61P31/14A61P31/18A61P35/00A61P37/02C07C229/56C07C229/64C07C311/46C07D215/56C07D265/26C07D285/24C07D413/06C07D417/04C07D417/14C07D491/04C07D521/00C07F7/18
CPCC07C2101/02C07D265/26C07D215/56C07C229/56C07D413/06C07D417/14C07D491/04C07D231/12C07D249/08C07D233/56C07C311/46C07D285/24C07D417/04C07F7/1856C07C2601/02C07F7/1804A61P1/16A61P29/00A61P31/00A61P31/12A61P31/14A61P31/18A61P35/00A61P37/00A61P37/02
Inventor 柴德平迈克尔·G·达西达什扬特·达纳克凯文·J·达菲格雷格·A·埃克里森杜克·M·菲奇亚当·T·盖茨维克托·K·约翰斯顿罗伯特·T·萨里斯基马修·J·夏普安东尼·N·肖罗莎娜·特德斯科肯尼思·J·威加尔迈克尔·N·齐默尔曼
Owner SMITHKLINE BECKMAN CORP
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