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

Modified 2' and 3' -nucleoside produgs for treating flaviridae infections

A technology of medicinal salts and compounds, applied in the field of 2' and/or 3' prodrugs, which can solve problems such as large side effects

Inactive Publication Date: 2006-04-19
INDENIX PHARM LLC +3
View PDF76 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, as with monotherapy, in combination therapy, considerable side effects occur, including hemolysis, influenza-like symptoms, anemia, and fatigue (GaryL. Davis. Gastroenterology 118:S104-S114, 2000)

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
  • Modified 2' and 3' -nucleoside produgs for treating flaviridae infections
  • Modified 2' and 3' -nucleoside produgs for treating flaviridae infections
  • Modified 2' and 3' -nucleoside produgs for treating flaviridae infections

Examples

Experimental program
Comparison scheme
Effect test

example

[0768] Non-limiting examples include:

[0769] 1) Protease inhibitors

[0770]Examples include substrate-based NS3 protease inhibitors (Attwood et al, Antiviral peptide derivatives (antiviral peptide derivatives), PCT WO 98 / 22496, 1998; Attwood et al., Antiviral Chemistry and Chemotherapy 1999, 10, 259-273; Attwood et al. ., Preparation and use of amino acid derivatives as anti-viralagents (preparation and use as an amino acid derivative of an antiviral agent), German Patent Publication No. DE 19914474; Tunget al., Inhibitiors of serine proteases, particularly hepatitis C virus NS3 proteases (inhibitors of serine proteases, especially hepatitis C virus NS3 protease), PCT WO 98 / 17679), including α-ketoamides and hydrazinoureas, and terminating electrophiles such as boronic acid or phosphonate (Llinas-Brunet et al, Hepatitis C inhibitor peptide analogues (hepatitis C virus inhibitor peptide analogs), PCT WO 99 / 07734); non-substrate-based NS3 protease inhibitors such as 2,4,6-tr...

Embodiment 1

[0880] The following examples illustrate the invention by way of illustration. It will be understood by those of ordinary skill in the art that these examples do not limit the invention and that changes may be made in details without departing from the spirit and scope of the invention. Example 1: Preparation of 1′-C-methyl riboadenine by 6-amino-9-(1-deoxy-β-D-psicofuranosyl) purine

[0881] Melting points were determined on a Mel-temp II apparatus and are uncorrected. On the Bruker400 AMX spectrometer, use 400MHz 1 H NMR and 100MHz 13C NMR, NMR spectra were recorded with TMS as internal standard. Chemical shifts (δ) are expressed in parts per million (ppm) and signals are expressed as s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), or bs (broad singlet). Infrared (IR) spectra were measured on a Nicolet 510P Fourier transform infrared (FT-IR) spectrometer. Mass spectra were recorded on a Micromass Autospec high resolution mass spectrometer. Thin laye...

Embodiment 2

[0904] Example 2: Preparation of 2'-C-methylribose-8-methyladenine

[0905] The target compound can be obtained according to the published method (R.E.Harry-O'kuru, J.M.Smith, and M.S.Wolfe, "A short, flexible route toward 2'-C-branched ribonucleosides", J.Org.Chem.1997, 62 , 1754-1759) prepared. (Process 9).

[0906] Process 9

[0907]

[0908] (a) Dess-Martin periodinane; (b) MeMgBr / TiCl 4 ; (c) BzCl, DMAP, Et 3 N; (d) bis(trimethylsilyl)acetamide, N 6 - Benzoyl adenine, TMSOTf; (e)NH 3 / MeOH

[0909] The 3'-prodrug of the 2'-branched nucleoside can be prepared according to the published method (Syntetic Communications, 1978, 8(5), 327-333; J.Am.Chem.Soc., 1999, 121(24) , 5661-5664) preparation. Alternatively, the 2'-branched nucleosides can be esterified without protection (Scheme 9b). Carbonyldiimidazole (377 mg, 2.33 mmol) was added to 15 ml of a solution of N-(tert-butoxycarbonyl)-L-valine (507 mg, 2.33 mmol) in anhydrous THF. T...

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

2' and / or 3'-prodrugs of 1', 2', 3' or 4'-branched nucleosides, and their pharmaceutically acceptable salts and derivatives are described. These prodrugs are used in the prophylaxis and treatment of Flaviviridae infections, including HCV infections, and other related conditions. Compounds and compositions of the prodrugs of the invention are described. Also provided are methods and uses comprising administering an effective amount of a prodrug of the invention, or a pharmaceutically acceptable salt or derivative thereof. These agents may optionally be administered in combination or alternately with other antiviral agents to prevent or treat flavivirus infection and other related conditions.

Description

[0001] Cross References to Related Applications [0002] This application claims U.S. Provisional Application No. 60 / 392,350, filed June 28, 2002; U.S. Provisional Application No. 60 / 466,194, filed April 28, 2003; and U.S. Provisional Application No. 60 / 470,949, the disclosure of each of which is hereby incorporated by reference. field of invention [0003] The present invention relates to the field of medicinal chemistry, in particular, to 6-modified 1', 2', 3' or 4'-branched pyrimidine nucleosides or 8- 2' and / or 3' prodrugs of modified 1', 2', 3' or 4'-branched purine nucleosides. Background of the invention [0004] Flaviviridae [0005] The Flaviviridae family of viruses comprises at least three separate genera: pestiviruses, which cause disease in cattle and pigs; flaviviruses, which are major causes of diseases such as dengue and yellow fever; and hepatic Viruses (hepaciviruses), the only member of which is the hepatitis C virus (HCV). The Flavivirus genus compris...

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): C07H19/06C07H19/10C07H19/16C07H19/20C07H19/04C07H19/044C07H19/048C07H19/052C07H19/056C07H19/12C07H19/14C07H19/22C07H19/23A61K31/7056A61K31/706A61K31/7064A61P31/14
CPCY02A50/30
Inventor 让-皮埃尔·索马多西波罗·拉科拉理查德·斯托勒吉勒·戈瑟兰
Owner INDENIX PHARM LLC
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