EP2321329A2 - Nouveaux derives de glucopyranose, leur preparation et leurs applications biologiques - Google Patents

Nouveaux derives de glucopyranose, leur preparation et leurs applications biologiques

Info

Publication number
EP2321329A2
EP2321329A2 EP09786642A EP09786642A EP2321329A2 EP 2321329 A2 EP2321329 A2 EP 2321329A2 EP 09786642 A EP09786642 A EP 09786642A EP 09786642 A EP09786642 A EP 09786642A EP 2321329 A2 EP2321329 A2 EP 2321329A2
Authority
EP
European Patent Office
Prior art keywords
formula
compound
methoxy
preparation
tert
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP09786642A
Other languages
German (de)
English (en)
French (fr)
Inventor
Robert Vachy
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of EP2321329A2 publication Critical patent/EP2321329A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/02—Acyclic radicals, not substituted by cyclic structures
    • C07H15/04—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
    • C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
    • C07H13/08—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals directly attached to carbocyclic rings

Definitions

  • the present invention relates to novel glucopyranose derivatives, in particular a novel ester, "3,4,5-trihydroxy-6-methoxy tetrahydropyran-2-yl methyl 3,5-di-tert-butyl-4-hydroxybenzoate" and derivatives of said ester.
  • the invention also relates to their method of preparation, as well as the biological applications of said compound and its derivatives, in particular for the treatment of viral and retroviral infections.
  • the new derivative of the invention has a developed formula close to the sweet compound D-glucopyranose previously described in FR 2 887 249 in the name of the Applicant, and the use of which is particularly advantageous against infections with enveloped viruses, and in particular the herpes virus, AIDS, influenza, hepatitis B and C.
  • the object of the invention is therefore to provide new active compounds against enveloped viruses.
  • the present invention more particularly relates to the 3,4,5-trihydroxy-6-methoxy tetrahydropyran-2-yl methyl 3,5-di-tert-butyl-4-hydroxybenzoate compound defined by the following formula (I):
  • the compound of the invention may also be in the form of a derivative such as, for example, in the form of a salt or an acid of said ester (I).
  • the compound (I) of the invention as well as said derivative (s) may be presented in a composition comprising at least one pharmaceutically acceptable excipient.
  • the subject of the invention is also a composition comprising at least one compound as defined above in association with a biologically active compound.
  • biologically active compounds mention may be made of:
  • the invention further relates to a pharmaceutical composition containing a therapeutically effective amount of at least one compound or at least one composition as defined above.
  • the amount of compound or composition may vary depending on the intended applications, the age and weight of the patient.
  • the pharmaceutical composition of the invention may be in a form suitable for oral, injectable or parenteral administration.
  • the present invention also covers the use of a compound or a composition as defined above, for the preparation of a medicament for the treatment and / or prevention of infections with enveloped viruses.
  • the invention also relates to a process for the preparation of the novel 3,4,5-trihydroxy-6-methoxy tetrahydropyran-2-yl methyl 3,5-di-tert-butyl-4-hydroxybenzoate ester of formula (I).
  • This process comprises the prior steps of forming 3,5-di-tert-butyl-4-hydroxybenzoic acid chloride of formula (IiI) on the one hand and [6-methoxy-3,4,5-tris- ( 4-methoxy-benzyloxy) -tetrahydropyran-2-yl3-methanoi of formula (V) on the other hand, then a coupling reaction between the two compounds (III) and (V) thus obtained to obtain the protected ester (II) which after deprotection leads to the glucopyranose compound (I) of the invention.
  • the preparation of the acid chloride (III) is carried out at from 3,5-di-tert-butyl-4 'hydroxybenzoic acid of the formula ((V):
  • This acid (IV) has been proposed to prepare antiviral drugs for the treatment of diseases related to an infection of an individual with viruses such as herpes or AIDS.
  • the preparation of compound (V) more particularly comprises the following steps: reaction of 3A5-trihydroxy-6-methoxy-tetrahydropyran-2-yl methanol of formula (VIII ):
  • the compound (I) of the present invention has several advantages, in particular with respect to the compound of the patent FR 2 887 249 of rather similar structure: a better solubility in water which facilitates the preparation of a pharmaceutical preparation more suitable for a drug,
  • FIG. 1 shows the synthesis scheme of the new ester (I).
  • EXAMPLE 1 SYNTHESIS OF 3,5-DI-TERTIOBUTYL-4-HYDROXYBENZOATE OF 3A5-TRIHYDROXY-6-M ETHOXY TETRAHYDRQPYRAN-2-YL METHYL OF FORMULA FI) (see FIG. 1).
  • Step 1 Synthesis of 6-methoxy-2- (4-methoxy-phenyl) -hexahydro-pyrano [3,2-D] [1,3] dioxin-7,8-diol of formula (VII).
  • pressure 40 mbar
  • Step 2 Synthesis of 6-methoxy-7,8-bis (4-methoxy-benzyloxy) -2- (4-methoxy-phenyl) -hexahydro-pyrano [3,2-D] [1,3] dioxin of formula (VI). Protection of the two free secondary alcohol functions of the compound (VII) is carried out by the action of sodium hydride and p-methoxybenzyl chloride (X) in a DMF / THF mixture (80/20).
  • Step 3 Synthesis of [6-methoxy-3,4,5-tris- (4-methoxybenzyloxy) tetrahydropyran-2-yl] methanol of formula (V).
  • the selective opening of the previously formed acetal (VI) is carried out by sodium cyanoborohydride and chlorotrimethylsilane in the presence of 3'-molecular sieve in acetonitrile.
  • the reaction is carried out in 1 hour at -20 ° C., and after basic treatment followed by purification on silica gel, the open product (V) is isolated in the form of a white solid with a yield of 60%.
  • the coupling between the acid chloride (ill) pre-prepared and the open compound (V) is carried out in the presence of 1.5 equivalents of triethylamine (Et 3 N) in dichloromethane (CH 2 Ck) at room temperature in 2 hours.
  • the coupling product (II) (3,4,5-tris (4-methoxybenzyloxy) -6-methoxytetrahydropyran-2-ylmethyl) 3,5-di-tert-butyl-4-hydroxybenzoate is isolated by chromatography on silica gel in the form of a yellow oil with a yield of 70%.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Virology (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Communicable Diseases (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Oncology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • AIDS & HIV (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
EP09786642A 2008-08-12 2009-07-20 Nouveaux derives de glucopyranose, leur preparation et leurs applications biologiques Withdrawn EP2321329A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0804572A FR2934998B1 (fr) 2008-08-12 2008-08-12 Nouveaux derives de glucopyranose, leur preparation et leurs applications biologiques
PCT/IB2009/053131 WO2010018474A2 (fr) 2008-08-12 2009-07-20 Nouveaux derives de glucopyranose, leur preparation et leurs applications biologiques

Publications (1)

Publication Number Publication Date
EP2321329A2 true EP2321329A2 (fr) 2011-05-18

Family

ID=40524524

Family Applications (1)

Application Number Title Priority Date Filing Date
EP09786642A Withdrawn EP2321329A2 (fr) 2008-08-12 2009-07-20 Nouveaux derives de glucopyranose, leur preparation et leurs applications biologiques

Country Status (7)

Country Link
US (1) US20110136748A1 (ja)
EP (1) EP2321329A2 (ja)
JP (1) JP2011530579A (ja)
CN (1) CN102149723A (ja)
CA (1) CA2734191A1 (ja)
FR (1) FR2934998B1 (ja)
WO (1) WO2010018474A2 (ja)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9278989B2 (en) 2012-03-08 2016-03-08 Kyushu University Sugar-derived gelator
CN111658631A (zh) * 2020-06-11 2020-09-15 广东盛普生命科技有限公司 没食子酸及其衍生物和结构类似物在制备抗冠状病毒药物方面的应用

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4870157A (en) 1985-07-09 1989-09-26 Olin Corporation Selected 4-acyl-2,6-dialkylphenol adducts of saccharides and their use as stabilizers of organic materials against oxidative degradation

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4833155A (en) * 1986-11-25 1989-05-23 Syntex (U.S.A.) Inc. 3-(ω-(3,5,-di-t-butyl-4-hydroxyphenyl)-alkanoyl)pyrroles, and anti-inflammatory uses thereof
US5312837A (en) * 1991-01-29 1994-05-17 Genelabs Technologies, Inc. Method of treating viral infections with aryl macrocyclic compounds
FR2887249B1 (fr) * 2005-06-21 2007-09-28 Rdw Pharma Soc Par Actions Sim Compose d-glucopyranose 1-[3,5-bis(1,1-dimenthylethyl)-4- hydroxybenzoate] et ses derives, leur preparation et leurs utilisations

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4870157A (en) 1985-07-09 1989-09-26 Olin Corporation Selected 4-acyl-2,6-dialkylphenol adducts of saccharides and their use as stabilizers of organic materials against oxidative degradation

Also Published As

Publication number Publication date
FR2934998B1 (fr) 2010-09-03
FR2934998A1 (fr) 2010-02-19
US20110136748A1 (en) 2011-06-09
WO2010018474A2 (fr) 2010-02-18
CN102149723A (zh) 2011-08-10
WO2010018474A3 (fr) 2010-04-29
JP2011530579A (ja) 2011-12-22
CA2734191A1 (fr) 2010-02-18

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