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

Macrocyclic inhibitors of flaviviridae viruses

A kind of cycloalkyl and heterocycloalkyl technology, applied in the field of macrocyclic inhibitors of Flaviviridae viruses

Active Publication Date: 2015-07-15
GILEAD SCI INC +1
View PDF11 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, none of sanglifehrin or its derivatives have been used in human antiviral therapy

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
  • Macrocyclic inhibitors of flaviviridae viruses
  • Macrocyclic inhibitors of flaviviridae viruses
  • Macrocyclic inhibitors of flaviviridae viruses

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0248] Preparation of macrocycles

[0249] Compounds of the invention, such as those of general formula I, II, II-a, II-b, II-c or III, can be prepared according to the schemes described below, but it will be appreciated that the illustrated methods or other method improvement. As illustrated in Scheme 1, from the five key components A-E, the protective group (PG 1 -PG 8 ), and combine them in order to synthesize the macrocyclic compound M. The dashed lines numbered 1-5, referred to herein as connection 1, connection 2, etc. respectively, are the 5 connections used to bind components A-E. The order in which a particular linkage occurs can vary and depends on the choice of protecting group and the desired chemistry. Typically, ligation 3, 4 or 5 is used as the final macrocyclization step.

[0250] plan 1

[0251]

[0252] Links 1 and 2 are amide bonds. Linkages are formed between the respective acids and amines using standard peptide coupling reagents known to those s...

Embodiment 1

[0466] Example 1: (E)-(2R,3R)-7-(3-{(R)-1-[((S)-hexahydro-pyridazine-3-carbonyl)-amino]-ethyl}- Phenyl)-3-methoxy-2-methyl-hept-6-enoic acid (S)-2-methyl-1-((S)-1-methyl-2-oxo-ethylaminomethyl acyl)-propyl ester- compound 1

[0467]

[0468] Synthesis of compound 1a: Preparation of 1-((1R,5S)-10,10-dimethyl-3,3-dioxo-3λ*6*-thio-4-aza-tricyclo in toluene (50 mL) A solution of [5.2.1.0*1,5*]dec-4-yl)-propan-1-one (3.95 g, 14.55 mmol) was then evaporated to dryness. This process was repeated, and the resulting white solid was dissolved in anhydrous dichloromethane (16 mL). A small amount of calcium hydride was added, followed by tert-butyldimethylsilyl trifluoromethanesulfonate (3.83 mL, 14.5 mmol) and anhydrous triethylamine (2.33 mL, 16.7 mmol). The reaction mixture was stirred at room temperature ("RT") for 15 hours ("h") under a nitrogen atmosphere. The resulting solution was evaporated to yield a thick paste which was redissolved in anhydrous dichloromethane (15 mL) a...

Embodiment 2

[0491] Embodiment 2: compound 2

[0492]

[0493] Synthesis of compound 2a: Preparation of 1-((1R,5S)-10,10-dimethyl-3,3-dioxo-3λ*6*-thia-4-nitrogen in anhydrous dichloromethane (24ml) A solution of hetero-tricyclo[5.2.1.0*1,5*]dec-4-yl)-propan-1-one (6.0 g, 22.1 mmol) and addition of tert-butyldimethylsilyltrifluoromethanesulfonic acid (5.0 mL, 22.1 mmol), followed by the addition of anhydrous triethylamine (3.54 mL, 25.4 mmol). The reaction mixture was stirred at room temperature under nitrogen atmosphere for 15 h. This gave a dark solution which evaporated to an oil. The oil was dissolved in anhydrous dichloromethane (22 mL), and the solution was added dropwise to crotonaldehyde (3.66 mL, 44.2 mmol) and Titanium tetrachloride (1M in dichloromethane, 44.2 mL, 44.2 mmol). The reaction mixture was stirred at -78 °C for 1 h, then ammonium chloride solution (30 mL) was added. The reaction mixture was allowed to warm to room temperature and the layers were separated. 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

Provided are compounds of Formula I: and pharmaceutically acceptable salts and esters thereof. The compounds, compositions, and methods provided are useful for the treatment of virus infections, particularly hepatitis C infections.

Description

[0001] Cross References to Related Applications [0002] Pursuant to 35 U.S.C. §119(e), this application claims the benefit of U.S. Provisional Application Serial No. 61 / 657,562, filed June 08, 2012, the entire contents of which are hereby incorporated by reference. technical field [0003] The application provides novel compounds that inhibit viruses, compositions comprising such compounds, and methods of treatment comprising administering such compounds. Background technique [0004] RNA viruses comprising the family Flaviviridae comprise at least three distinguishable genera, including pestiviruses, flaviviruses and hepaciviruses (Calisher et al., J. Gen. Virol. 1993, 70, 37-43). Although pestisviruses cause many economically important animal diseases such as bovine viral diarrhea virus (BVDV), classical swine fever virus (CSFV, hog cholera) and sheep border disease (BDV), their importance in human disease Few have been adequately characterized (Moennig, V. et al., Adv....

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): C07D487/08C07D498/08C07D498/18C07D498/22A61K31/504A61P31/14
CPCC07D487/08A61K38/15C07D498/08A61K38/12C07D498/22C07D498/18A61K45/06A61K39/29C07K5/02C07D513/18A61K38/00A61P1/14A61P1/16A61P11/00A61P29/00A61P3/04A61P31/00A61P31/12A61P31/14A61P31/18A61P31/20A61P35/00A61P37/02A61P43/00Y02A50/30A61K31/504A61K39/05C07K5/0202
Inventor 维多利亚 亚历山德拉·斯特德曼卡琳 G.·波尔伦尼克利诺斯·拉扎里迪斯卡洛琳·阿西罗大卫 肯尼斯·迪安安德鲁 约翰·基茨达斯汀 斯科特·西格尔亚当 詹姆斯·施里尔理查德·麦肯曼彼得·扬萨格雷戈里·瓦特艾德里安 约翰·海顿简 伊夫斯·齐瓦
Owner GILEAD SCI INC
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