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1. WO2005003374 - SYNTHESE DE NUCLEOSIDES ?-L-2-DESOXY

Numéro de publication WO/2005/003374
Date de publication 13.01.2005
N° de la demande internationale PCT/US2004/021281
Date du dépôt international 30.06.2004
Demande présentée en vertu du Chapitre 2 28.01.2005
CIB
C07H 19/00 2006.01
CCHIMIE; MÉTALLURGIE
07CHIMIE ORGANIQUE
HSUCRES; LEURS DÉRIVÉS; NUCLÉOSIDES; NUCLÉOTIDES; ACIDES NUCLÉIQUES
19Composés contenant un hétérocycle partageant un hétéro-atome du cycle avec un radical saccharide; Nucléosides; Mononucléotides; Leurs anhydro-dérivés
CPC
C07H 13/04
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
13Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
02by carboxylic acids
04having the esterifying carboxyl radicals attached to acyclic carbon atoms
C07H 13/08
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
13Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
02by carboxylic acids
08having the esterifying carboxyl radicals directly attached to carbocyclic rings
C07H 15/203
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
15Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
20Carbocyclic rings
203Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems
C07H 19/06
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
19Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides ; Anhydro-derivatives thereof
02sharing nitrogen
04Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
06Pyrimidine radicals
C07H 19/073
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
19Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides ; Anhydro-derivatives thereof
02sharing nitrogen
04Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
06Pyrimidine radicals
073with 2-deoxyribosyl as the saccharide radical
C07H 19/09
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
19Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides ; Anhydro-derivatives thereof
02sharing nitrogen
04Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
06Pyrimidine radicals
09with arabinosyl as the saccharide radical
Déposants
  • IDENIX (CAYMAN) LIMITED; Walker Secretaries Walker House Grand Cayman, KY (AllExceptUS)
  • STORER, Richard [GB/GB]; GB (UsOnly)
  • MOUSSA, Adel [US/US]; US (UsOnly)
  • WANG, Jing, Yang [CN/US]; US (UsOnly)
  • CHAUDHURI, Narayan [IN/US]; US (UsOnly)
  • MATHIEU, Steven [US/US]; US (UsOnly)
  • STEWART, Alistair [GB/US]; US (UsOnly)
Inventeurs
  • STORER, Richard; GB
  • MOUSSA, Adel; US
  • WANG, Jing, Yang; US
  • CHAUDHURI, Narayan; US
  • MATHIEU, Steven; US
  • STEWART, Alistair; US
Mandataires
  • KNOWLES, Sherry, M.; King & Spalding LLP 191 Peachtree Street, 45th Floor Atlanta, GA 30303-1763, US
Données relatives à la priorité
60/483,71130.06.2003US
60/558,61601.04.2004US
Langue de publication anglais (EN)
Langue de dépôt anglais (EN)
États désignés
Titre
(EN) SYNTHESIS OF &bgr;-L-2-DEOXY NUCLEOSIDES
(FR) SYNTHESE DE NUCLEOSIDES ?-L-2-DESOXY
Abrégé
(EN)
An improved process for the preparation of 2'-modified nucleosides and 2'-deoxy-nucleosides, such as, &bgr;-L-2'-deoxy-thymidine (LdT), is provided. In particular, the improved process is directed to the synthesis of a 2'-deoxynucleoside that may utilize different starting materials but that proceeds via a chloro-sugar intermediate or via a 2,2'­ anhydro-1-furanosyl-nucleobase intermediate. Where an 2,2'-anhydro-1-furanosyl base intermediate is utilized, a reducing agent, such as Red-Al, and a sequestering agent, such as 15-crown-5 ether, that cause an intramolecular displacement reaction and formation of the desired nucleoside product in good yields are employed. An alternative process of the present invention utilizes a 2,2'-anhydro-1-furanosyl base intermediate without a sequestering agent to afford 2'-deoxynucleosides in good yields. The compounds made according to the present invention may be used as intermediates in the preparation of other nucleoside analogues, or may be used directly as antiviral and/or antineoplastic agents.
(FR)
Cette invention concerne une technique améliorée de préparation de nucléosides modifiés en 2' et de nucléosides 2'-désoxy, tels que la ß-L-2'-désoxy-thymidine (LdT). Cette technique concerne en particulier la synthèse d'un nucléoside 2'-désoxy qui peut utiliser différents matériaux de départ, mais qui se fait via un intermédiaire de chloro-sucre ou un intermédiaire d'une nucléobase de 2,2'- anhydro-1-furanosyle. Dans le cas d'un intermédiaire d'une base de 2,2'-anhydro-1-furanosyle, on utilise un agent réducteur tel que Red-Al, et un agent séquestrant tel qu'un éther15-couronne-5 qui provoquent une réaction de déplacement intramoléculaire et la formation abondante du produit nucléosidique recherché. En variante, on peut utiliser un intermédiaire de base 2,2'-anhydro-1-furanosyle sans agent séquestrant pour obtenir de bons rendements de 2'-désoxy nucléosides. Les composés obtenus selon la présente invention peuvent être utilisés comme intermédiaires pour l'obtention d'autres analogues de nucléosides, ou bien directement en tant qu'agents antiviraux et/ou anti-néoplasiques.
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