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

Macrocyclic inhibitors of flaviviridae viruses

A spirocycle, heterocycloalkyl technology, applied in the field of macrocycle inhibitors of Flaviviridae viruses

Inactive Publication Date: 2015-06-10
GILEAD SCI INC +1
View PDF14 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

[0260] Preparation of macrocycles

[0261] Compounds of the invention, such as those of general formula (I) and (II), may be prepared according to the schemes described below, although it will be appreciated that modifications of the illustrated methods or other methods may also be used. 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 (Q is NH). 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.

[0262] plan 1

[0263]

[0264] Linkages 1, 2 and 3 are amide bonds. Linkages are formed between representative acids and amines using standard peptide coupling ...

Embodiment 1 to 20

[0365] For Examples 1 to 20, unless otherwise noted, preparative HPLC was performed on a Gilson HPLC system using an Agilent Eclipse XDB / C187micron, 250 x 21.2 mm semi-preparative column and an acetonitrile / water mobile phase at a flow rate of 20 mL / min.

[0366] For Examples 121 to 175, unless otherwise noted, preparative HPLC was performed on a Shimadzu HPLC system using a 21.2 x 250 mm 10 micro C18 Phenomenex Gemini semi-preparative column and an acetonitrile / water mobile phase at a flow rate of 20 mL / min.

[0367] List of Abbreviations and Acronyms

[0368] Abbreviation Meaning

[0369] ℃ degrees Celsius

[0370] di-tBuXPhos 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2′,4′,6′-triisopropyl-1,1′-bis

[0371] benzene

[0372] 2,6-lut. 2,6-lutidine

[0373] MNBA 2-methyl-6-nitrobenzoic anhydride

[0374] 4AMS 4 angstrom molecular sieve

[0375] Acetyl

[0376] ACN acetonitrile

[0377] app obvious

[0378] Aq water content

[0379] BINAP (2,2'-bis(biph...

Embodiment 1

[0503] Example 1: (E)-(2R,5S,11S,14S,17R,18R)-18-hydroxy-14-isopropyl-2,11,17-trimethyl-3,9,12,15, 28-Pentaza-tricyclo[21.3.1.1*5,9*]octadeca-1(26),21,23(27),24-tetraene-4,10,13,16-tetraone : Compound 1

[0504]

[0505] Preparation of 1-((1R,5S)-10,10-dimethyl-3,3-dioxo-3λ*6*-thio-4-aza-tricyclo[5.2.1.0* in toluene (50 mL) A solution of 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 RT ("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) and added dropwise to anhydrous dichloromethane (20 mL ) in a...

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] This application claims the benefit of US Provisional Application Serial No. 61 / 657,562 filed June 8, 2012 under 35 U.S.C. § 119(e), which is incorporated herein by reference in its entirety. technical field [0003] The application provides novel compounds that inhibit viruses, compositions containing such compounds, and methods of treatment involving the administration of 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. Vir. Res. ...

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): C07D487/18C07D498/18A61K31/504A61P31/12A61P35/00
CPCC07D487/18C07D498/18A61K38/21A61K38/12C07K5/06052A61P1/16A61P11/00A61P29/00A61P3/04A61P31/00A61P31/12A61P31/14A61P31/18A61P35/00A61P37/02A61P43/00Y02A50/30A61K31/504A61K45/06C07K5/06086C07K5/06139C07K5/06191
Inventor 卡洛琳·阿西罗维多利亚 亚历山德拉·斯特德曼西蒙 尼尔·佩蒂特卡琳 G.·波尔伦尼克利诺斯·拉扎里迪斯大卫 肯尼斯·迪安尼尔 安德鲁·邓巴艾德里安 约翰·海顿安德鲁 约翰·基茨达斯汀 斯科特·西格尔卡皮尔 库马尔·卡尔基亚当 詹姆斯·施里尔彼得·扬萨理查德·麦肯曼简 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