WO2013167743A1 - Utilisation de composés pour le traitement de la douleur - Google Patents

Utilisation de composés pour le traitement de la douleur Download PDF

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Publication number
WO2013167743A1
WO2013167743A1 PCT/EP2013/059752 EP2013059752W WO2013167743A1 WO 2013167743 A1 WO2013167743 A1 WO 2013167743A1 EP 2013059752 W EP2013059752 W EP 2013059752W WO 2013167743 A1 WO2013167743 A1 WO 2013167743A1
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Prior art keywords
pain
compound
group
amino
methyl
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PCT/EP2013/059752
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English (en)
Inventor
Henrik Nilsson
Shane Mcmanus
Arif MUHAMED
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Akron Molecules Gmbh
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Priority to JP2015510836A priority Critical patent/JP2015520144A/ja
Priority to AU2013257951A priority patent/AU2013257951A1/en
Priority to EP13721770.9A priority patent/EP2846788A1/fr
Publication of WO2013167743A1 publication Critical patent/WO2013167743A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
    • A61K31/708—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • the present invention relates to the field of method of treatment of pain and the provision of pharmaceutical compounds suitable for such treatments.
  • Nociception the detection of noxious or damaging stimuli serves a crucial biological purpose: it alerts living organisms to environmental dangers, inducing the sensation of pain, reflex withdrawal and complex behavioural and emotional responses, which protect the organism from further damage.
  • Noxious stimuli are detected by specialized high thresh ⁇ old primary sensory neurons (nociceptors) , which transfer sig ⁇ nals to the spinal cord and then transmit them to the brain for higher level processing that results in the conscious awareness of the sensation called pain.
  • the functional importance of pain perception is exemplified by individuals with defects in noci ⁇ ception; patients with congenital insensitivity to pain do not survive past their twenties.
  • Acute or nociceptive pain is generally self-limiting and serves a protective biological function by warning of on ⁇ going tissue damage caused by noxious chemical, thermal and me ⁇ chanical stimuli.
  • nociceptive pain include: post ⁇ operative pain, pain associated with trauma, and the pain asso ⁇ ciated with arthritis.
  • Chronic pain serves no protective biological function, and reflects either poor res ⁇ olution of the painful stimuli, or is itself a disease process. Chronic pain is unrelenting and not self-limiting and can persist for years and even decades after the initial injury.
  • Chron ⁇ ic pain is predominantly neuropathic in nature and may involve damage either to the peripheral or central nervous systems.
  • Chronic pain may, however, also be nociceptive, such as inflam ⁇ matory in nature. Furthermore, chronic pain may also be mixed nociceptive and neuropathic. Finally, chronic pain may also be of a central origin, deriving from processes/conditions in the central or peripheral nervous system, such as e.g. post stroke pain or post-amputation pain/phantom limb pain, which may, however, also be considered neuropathic in nature.
  • therapies for pain have a number of dis ⁇ advantages, which warrant the development of new therapies for the treatment, prevention and/or reduction of pain. The disadvantages are different for the different classes of available drugs.
  • NSAIDs non-steroidal anti-inflammatory drugs
  • GI gastrointestinal
  • CV cardiovascular
  • ⁇ -opioid receptor agonists opioid and opiates
  • Anti-depressants e.g. tricyclic anti-depressants (TCAs) , such as nortriptyline and desipramine, as well as the selective serotonin norepinephrine reuptake inhibitors (SSNRIs) , including e.g.
  • venlafaxaine may have a negative impact on car ⁇ diac function or, as in the case of the SSNRI duloxetine, may induce nausea.
  • Anti-convulsants such as pregabalin and gapa- bentin, can induce somnolence.
  • the disadvantage for any of the existing available drugs may also be related to limited efficacy in treating and/or preventing pain.
  • the present invention therefore provides the use of new classes of compounds for the treatment, prevention or reduction of pain.
  • the present invention also provides a method of treat ⁇ ing pain in a subject comprising the administration of a therapeutic compound selected from the inventive compounds.
  • the present invention provides the use of a com ⁇ pound of the invention for the manufacture of an analgesic or a medicament for the treatment of pain in a subject.
  • the invention is further defined by the subject matter of the claims.
  • the com ⁇ pounds of the invention are e.g. given in the claims and in the tables herein.
  • the compounds according to the invention are contemplated to have advantages in that they have less side effects as deter ⁇ mined by one or several of the side effects listed above for one or more of the available therapies.
  • Less side effects can be as ⁇ sessed e.g. either in terms of reduced severity and/or reduced frequency of side effects.
  • Such reduced side effects can e.g. be less somnolence c.f. anti-convulsants, fewer or less frequent cardiovascular side effects c.f. anti-depressants, less addic- tion potential c.f. ⁇ -opioid receptor agonists, less GI bleeding c.f. NSAIDs etc.
  • the compounds according to the invention are contemplated to have improved efficacy c.f. the available thera ⁇ pies. Improved efficacy can e.g. be determined as a greater num ⁇ ber of responders or greater magnitude of efficacy c.f. one or several of the existing therapies.
  • the compounds according to the in ⁇ vention are contemplated to have both reduced side effects and improved efficacy c.f. available therapies.
  • selected pain subtypes can be specifically treated by the inventive compounds.
  • Example inventive compounds are selected from the groups of a) nucleotide analogues, b) nucleoside analogues, c) compounds that interact with DNA polymerase, or d) compounds that interact with DNA.
  • inventive com ⁇ pounds or salts thereof are identified by their unique CAS num ⁇ ber (Chemical Abstracts Service, www.cas.org).
  • the invention in ⁇ cludes any salt form of the given compounds, but preferably re ⁇ lates to the exact salt form as given in the tables.
  • Table 3 re ⁇ fers to both table 3a and 3b.
  • Further inventive compounds are defined as derivatives of a given formula as described below the tables .
  • HDP- (R) -PMPA HDP- (R) -PMPA
  • Cidofovir ( ⁇ [ (S) -1- (4-amino-2-oxo-l, 2- Cidofovir dihydropyrimidin-l-yl) -3- hydroxypropan-2- yl] oxyjmethyl) phosphonic acid
  • Ribavirin 1- (2R, 3R, 4S, 5R) -3, 4-dihydroxy-5- Ribavirin
  • Taribavirin 1- (2R, 3R, 4S, 5S) - 3, 4-dihydroxy-5- Taribavirin
  • PRO 140 Humanized monoclonal IgG4 kappa anti ⁇ body targeting human C-C chemokine
  • CCR5 CCR5 receptor type 5
  • HuPRO-140 HuPRO-140
  • Emtricita- 4-amino-5-fluoro-1- [ (2S, 5R) -2- Emtricita- bine / FTC (hydroxymethyl ) -1, 3-oxathiolan-5-yl ] - bine
  • ester hemifumarate or TAF; or GS- 7340-03
  • Nevirapine 1 l-cyclopropyl-4-methyl-5 , 11-dihydro- Nevirapine
  • Atevirdine [4- [3- (ethylamino) pyridin-2- Atevirdine yl ] piperazin-l-yl ] - (5-methoxy-lH- mesylate indol-2-yl) methanone
  • Table 3c active compounds (INN), List of Integrity Polymerase Inhibitors :
  • Table 3 consists of table 3a, 3b, 3c and 3d.
  • Preferred inventive compounds are Tomeglovir derivatives, Alamifovir or Alamifovir derivatives, Emtricitabine or Emtricit- abine derivatives, Entecavir or Entecavir derivatives, Adefovir or Adefovir derivatives, Cidofovir or Cidofovir derivatives, Tenofovir or Tenofovir derivatives.
  • Adefovir PMEA
  • Adefovir Dipivoxil Bis-POM PMEA
  • Active compounds Tenofovir (PMPA) is included or ex- eluded.
  • Pradefo- vir Remofovir, CAS 625095-60-5) is included or excluded.
  • the inventive compound is Tomeglovir (Synonym: BAY-38-4766; Chemical name: N- [4- [5- (Dimethylamino) -1- naphthylsulfonamido ] phenyl ] -3-hydroxy-2 , 2-dimethylpropionamide ; CAS number: 233254-24-5), or any derivatives, salts, prodrugs or metabolites of Tomeglovir.
  • Tomeglovir is an antiviral compound that was originally developed against Cytomegalovirus infection, and its antiviral properties are effected by the inhibition of viral terminase enzyme.
  • the Tomeglovir deriva ⁇ tive is selected from the derivatives as described in EP 1049666 Bl (incorporated herein by reference) , especially selected from t the formula (I) :
  • R and R are identical or different and represent hydrogen, formyl, phenyl or benzyl optionally substituted by one to three halogen atoms, or straight-chain or branched alkyl or acyl each having up to 6 carbon atoms, where alkyl or acyl can optionally be substituted by one to three substituents selected from halo ⁇ gen and hydroxyl,
  • A, D, E and G are identical or different and represent hydro ⁇ gen, halogen, nitro, cyano, hydroxyl, carboxyl, trifluoromethyl , trifluoromethoxy or straight-chain or branched alkyl, alkoxy or alkoxycarbonyl each having up to 5 carbon atoms,
  • R 3 represents straight-chain or branched alkenyl having up to 6 carbon atoms, or represents straight-chain or branched alkyl having up to 8 carbon atoms, which optionally carries an amino group which can optionally be substituted by alkyl having up to 4 carbon atoms or by an amino protective group, or the alkyl is optionally identically or differently substituted one to 3 times by hydroxyl, cyano, halogen, azido, nitro, trifluoromethyl , car ⁇ boxyl or phenyl which, for its part, can be identically or dif ⁇ ferently substituted up to 2 times by nitro, halogen, hydroxyl or by straight-chain or branched alkyl or alkoxy having up to 4 carbon atoms, or R 3 represents radicals of the formulae: in which
  • L represents a straight-chain or branched alkanediyl group having up to 6 carbon atoms
  • Q represents alkyl having up to 6 carbon atoms, which is op ⁇ tionally substituted by carboxyl, or represents radicals of the formulae :
  • a denotes the number 1 or 2
  • R 5 denotes hydrogen
  • R 6 denotes cycloalkyl having 3 to 8 carbon atoms or aryl having 6 to 10 carbon atoms or hydrogen, or denotes straight-chain or branched alkyl having up to 8 carbon atoms, where the alkyl is optionally substituted by cyano, methylthio, hydroxyl, mercapto, guanidyl or by a group of the formula -NR 9 R 10 or -R 11 -OC-,
  • R 9 and R 10 independently of one another denote hydrogen, straight-chain or branched alkyl having up to 8 carbon atoms or phenyl, and
  • R 11 denotes hydroxyl, benzyloxy, alkoxy having up to 6 carbon atoms or the abovementioned group -NR 9 R 10 ,
  • alkyl is optionally substituted by cycloalkyl having 3 to 8 carbon atoms or by aryl having 6 to 10 carbon atoms, which, for its part, is substituted by hydroxyl, halogen, nitro, alkoxy having up to 8 carbon atoms or by the group -NR 9 R 10 , in which
  • R 9 and R 10 have the meaning indicated above
  • the alkyl is optionally substituted by a 5- to 6-membered ni ⁇ trogen-containing heterocycle or by indolyl, in which the corre ⁇ sponding -NH functions are optionally substituted by alkyl hav ⁇ ing up to 6 carbon atoms or protected by an amino protective group, R 7 and R 8 are identical or different and denote hydrogen or an amino protective group,
  • R 4 denotes hydrogen or a radical of the formula
  • R 5' , R 6' , R 7' and R 8' have the meaning of R 5 , R 6 , R 7 and
  • X has the meaning of R 4 indicated above and can be identical to or different from this meaning
  • N- [4- [ [ [5- (dimethylamino) -1-naphthalenyl ] sulphonyl] - amino ] phenyl ] acetamide may be included or excepted from these compounds .
  • R 1 and R 2 are identical or different and represent hydrogen, phenyl or straight-chain or branched alkyl or acyl each having up to 6 carbon atoms,
  • A, D, E and G are identical or different and represent hydro ⁇ gen, halogen, nitro, cyano, hydroxyl, carboxyl, trifluoromethyl , trifluoromethoxy or straight-chain or branched alkyl, alkoxy or alkoxycarbonyl each having up to 5 carbon atoms,
  • R 3 represents straight-chain or branched alkenyl having up to 6 carbon atoms, or represents straight-chain or branched alkyl having up to 8 carbon atoms, which optionally carries an amino group which can be substituted by alkyl having up to 4 carbon atoms or by an amino protective group, or the alkyl is optional ⁇ ly identically or differently substituted one to 3 times by hy ⁇ droxyl, cyano, halogen, azido, nitro, trifluoromethyl , carboxyl or phenyl which, for its part, can be identically or differently substituted up to 2 times by nitro, halogen, hydroxyl or by straight-chain or branched alkyl or alkoxy having up to 4 carbon atoms, or
  • R 3 represents radicals of the formulae in which
  • L represents a straight-chain or branched alkanediyl group having up to 6 carbon atoms
  • Q represents alkyl having up to 6 carbon atoms, which is op ⁇ tionally substituted by carboxyl, or represents radicals of the formulae
  • a denotes the number 1 or 2
  • R 5 denotes hydrogen
  • R 6 denotes cycloalkyl having 3 to 8 carbon atoms or aryl having 6 to 10 carbon atoms or hydrogen, or
  • alkyl is optionally substituted by cyano, methylthio, hydroxyl, mercapto, guanidyl or by a group of the formula - NR 9 R 10 or -R ⁇ -OC-, in which
  • R 9 and R 10 independently of one another denote hydrogen, straight-chain or branched alkyl having up to 8 carbon atoms or phenyl, and
  • R 11 denotes hydroxyl, benzyloxy, alkoxy having up to 6 carbon atoms or the abovementioned group -NR 9 R 10 ,
  • alkyl is optionally substituted by cycloalkyl having 3 to 8 carbon atoms or by aryl having 6 to 10 carbon atoms which, for its part, is substituted by hydroxyl, halogen, nitro, alkoxy having up to 8 carbon atoms or by the group -NR 9 R 10 , in which
  • R 9 and R 10 have the meaning indicated above
  • the alkyl is optionally substituted by a 5- to 6-membered ni ⁇ trogen-containing heterocycle or by indolyl, in which the corre ⁇ sponding -NH functions are optionally substituted by alkyl hav ⁇ ing up to 6 carbon atoms or protected by an amino protective group, R 7 and R 8 are identical or different and denote hydrogen or an amino protective group,
  • R 4 represents hydrogen or a radical of the formula in which
  • R 5' , R 6' , R 7' and R 8' have the meaning of R 5 , R 6 , R 7 and R 8 indi ⁇ cated above and are identical to or different from these, and
  • R 3 represents straight-chain or branched alkenyl having up to 6 carbon atoms, or represents straight-chain or branched alkyl having up to 8 carbon atoms, in which the alkyl carries an amino group which can be substituted by alkyl having up to 4 carbon atoms or by an amino protective group, or the alkyl is identi ⁇ cally or differently substituted one to 3 times by hydroxyl, cy- ano, halogen, azido, nitro, trifluoromethyl , carboxyl or phenyl which, for its part, can be identically or differently substi ⁇ tuted up to 2 times by nitro, halogen or hydroxyl or by
  • R 3 represent radicals of the formulae
  • R 1 and R 2 are identical or different and represent hydrogen, phenyl or straight-chain or branched alkyl or acyl each having up to 5 carbon atoms
  • A, D, E and G are identical or different and represent hydro ⁇ gen, fluorine, chlorine, bromine, nitro, cyano, hydroxyl or straight-chain or branched alkyl, alkoxy or alkoxycarbonyl each having up to 3 carbon atoms,
  • R 3 represents straight-chain or branched alkenyl having up to 5 carbon atoms, or
  • alkyl represents straight-chain or branched alkyl having up to 7 carbon atoms which optionally carries an amino group which can be substituted by alkyl having up to 3 carbon atoms, tert- bu- tyloxycarbonyl or benzyloxycarbonyl , or the alkyl is optionally identically or differently substituted one to 3 times by hydrox ⁇ yl, cyano, fluorine, chlorine, azido, nitro, trifluoromethyl or phenyl which, for its part, can be identically or differently substituted up to 2 times by nitro, fluorine, chlorine or hy ⁇ droxyl or by straight-chain or branched alkyl or alkoxy having up to 3 carbon atoms, or
  • R 3 represent radicals of the formulae:
  • L represents a straight-chain or branched alkanediyl group having up to 4 carbon atoms
  • Q represents alkyl having up to 4 carbon atoms, which is op ⁇ tionally substituted by carboxyl, or represents radicals of the formulae :
  • a denotes the number 1 or 2
  • R 5 denotes hydrogen
  • R 6 denotes cyclopentyl, cyclohexyl, phenyl or hydrogen, or de ⁇ notes straight-chain or branched alkyl having up to 6 carbon atoms , where the alkyl can optionally be substituted by cyano, methyl- thio, hydroxyl, mercapto, guanidyl, amino, carboxyl or 3 ⁇ 4N-CO-, or the alkyl is substituted by cyclohexyl, naphthyl or phenyl which, for its part, can be substituted by fluorine, hydroxyl, nitro or alkoxy having up to 4 carbon atoms,
  • alkyl is substituted by indolyl, imidazolyl, pyridyl, triazolyl or pyrazolyl, where the corresponding -NH functions are optionally substituted by alkyl having up to 4 carbon atoms or protected by tert-butyloxycarbonyl or benzyloxycarbonyl ,
  • R 7 and R 8 are identical or different and denote hydrogen, tert- butyloxycarbonyl or benzyloxycarbonyl,
  • R 4 represents hydrogen or a radical of the formula:
  • R 5 , R 6 , R 7 and R 8 have the meaning of R 5 , R 6 , R 7 and R 8 indicated above and are identical to or different from these,
  • R 3 represents straight-chain or branched alkenyl having up to 5 carbon atoms, or
  • alkyl represents straight-chain or branched alkyl having up to 7 carbon atoms, in which the alkyl carries an amino group which can be substituted by alkyl having up to 3 carbon atoms, tert- butyloxycarbonyl or benzyloxycarbonyl, or the alkyl is identically or differently substituted one to 3 times by hydroxyl, cy ⁇ ano, fluorine, chlorine, azido, nitro, trifluoromethyl or phenyl which, for its part, can be identically or differently substi ⁇ tuted up to 2 times by nitro, fluorine, chlorine or hydroxyl or by straight-chain or branched alkyl or alkoxy having up to 3 carbon atoms, or
  • R 3 represents radicals of the formulae in which L and Q are as defined above.
  • R 1 and R 2 are identical or different and represent hydrogen, phenyl or straight-chain or branched alkyl or acyl each having up to 4 carbon atoms,
  • A, D, E and G are identical or different and represent hydro ⁇ gen, fluorine, chlorine, bromine, hydroxyl, methyl or methoxy,
  • R 3 represents straight-chain or branched alkenyl having up to 4 carbon atoms, or
  • R 3 represents radicals of the formulae
  • L represents a straight-chain or branched alkanediyl group having up to 4 carbon atoms
  • Q represents alkyl having up to 3 carbon atoms, which is op ⁇ tionally substituted by carboxyl, or
  • R 6 denotes cyclopentyl, cyclohexyl or hydrogen, or denotes straight-chain or branched alkyl having up to 4 carbon atoms, where the alkyl can optionally be substituted by cyano, methyl- thio, hydroxyl, mercapto, guanidyl, amino, carboxyl or 3 ⁇ 4N-CO-, or the alkyl is substituted by cyclohexyl, naphthyl or phenyl which, for its part, can be substituted by fluorine, chlorine or alkoxy having up to 4 carbon atoms,
  • alkyl is substituted by indolyl, imidazolyl, triazolyl, pyridyl or pyrazolyl, where the corresponding -NH functions are optionally substituted by methyl or protected by benzyloxymeth- ylene or tert-butyloxy-carbonyl (BOC) ,
  • R 7 and R 8 are identical or different and denote hydrogen or tert-butyloxycarbonyl ,
  • R 4 represents hydrogen or a radical of the formula V
  • R 5' , R 6' , R 7' and R 8' have the meaning of R 5 , R 6 , R 7 and
  • R 3 represents straight-chain or branched alkenyl having up to 4 carbon atoms, or
  • alkyl represents straight-chain or branched alkyl having up to 5 carbon atoms, in which the alkyl carries an amino group which can be substituted by tert-butyloxycarbonyl or benzyloxycarbonyl , or the alkyl is identically or differently substituted one to 3 times by hydroxyl, cyano, fluorine, chlorine, nitro, azido, tri- fluoromethyl or phenyl which, for its part, can be identically or differently substituted up to 2 times by nitro, fluorine, chlorine, hydroxyl, methyl; ethyl, methoxy or ethoxy, or
  • R 3 represents radicals of the formulae
  • R 1 and R 2 represent straight-chain or branched alkyl having up to 4 carbon atoms
  • A, D, E and G represent hydrogen
  • R 3 represents straight-chain or branched alkyl having up to 5 carbon atoms, which is substituted by hydroxyl, or
  • R 3 represents a radical of the formula -L-O-CO-Q in which
  • L represents a straight-chain or branched alkanediyl group having up to 4 carbon atoms
  • R 5 and R 6 denote hydrogen
  • R 7 and R 8 denote hydrogen
  • R 4 represents hydrogen
  • said compounds or intermediates or derivatives thereof are of the general formula (I) above, which are selected from the group of the following compounds :
  • the compound may be provided in a composition in association with a pharmaceutically acceptable substantially nontoxic carri ⁇ er or excipient.
  • the inventive compound is Alamifovir (Syno ⁇ nym: LY-582563, MCC-478; Chemical name: Bis (2,2,2- trifluoroethyl ) ( (2- (2-amino-6- ( (4-methoxyphenyl) sulfanyl) -9H- purin-9-yl) ethoxy) methyl) phosphonate ; Bis (2,2, 2-trifluoroethyl) ( (2- ⁇ 2-amino-6- ( (4-methoxyphenyl) sulfanyl) -9H-purin-9- yl ⁇ ethoxy) methyl phosphonate ; CAS number: 193681-12-8), or any derivatives, salts, prodrugs, metabolites of Alamifovir, includ ⁇ ing but not restricted to the prodrugs Alamifovir disoproxil fumarate and Alamifovir disoproxil hemifumarate, or x
  • Alamifovir is a purine nucleotide ana ⁇ logue antiviral compound that was originally developed against Hepatitis B virus infection, and its antiviral properties are effected by the inhibition of viral DNA polymerase enzyme.
  • Ala ⁇ mifovir disoproxil hemifumarate is a prodrug of Alamifovir, that has been in the preclinical phase of development in rodents, as an anti-Hepatitis B antiviral.
  • the derivative or salt or prodrug or metab ⁇ olite of Alamifovir is selected from the compounds as described in EP 0785208 Bl and EP 2511281 Al (all incorporated herein by reference) , especially selected from the compounds, or their salts or hydrates or solvates or intermediates thereof, of the formula I ) :
  • R 1 represents hydrogen atom, a C 1 -C6 alkoxy group, a Ci- C 4 alkoxy group substituted with one or more halogen atoms, a hal ⁇ ogen atom, amino group, or nitro group
  • R 2 and R 3 independently represent hydrogen atom, a C 1 -C22 alkyl group, an acyloxymethyl group, an acylthioethyl group, or an ethyl group substituted with one or more halogen atoms
  • R 4 represents hydrogen atom, a Ci- C4 alkyl group, a C 1 -C4 hydroxyalkyl group, or a C 1 -C4 alkyl group substituted with one or more halogen atoms
  • X represents a carbon atom or a nitrogen atom.
  • R 1 represents hydrogen atom or a C 1 -C6 alkoxy group.
  • R 1 represents hydrogen atom or a C 1 -C4 alkoxy group; and
  • R 2 and R 3 independently represent hydrogen atom, a Ci- C22 alkyl group, or an ethyl group substituted with one or more halogen atoms.
  • R 1 represents hydrogen atom or a C 1 -C4 alkoxy group
  • R 2 and R 3 independently represent hydrogen atom, a C 1 -C22 alkyl group, or 2 , 2 , 2-trifluoroethyl group
  • R 4 represents hydrogen atom or methyl group.
  • R 1 represents hydrogen atom or a C 1 -C4 alkoxy group
  • R 2 and R 3 independently represent hydrogen atom or 2,2,2- trifluoroethyl group
  • R 4 represents hydrogen atom or methyl group .
  • the compound is selected from the group consisting of:
  • R 1 is hydrogen atom or a C1-C4 alkoxy group
  • R 2 and R 3 represent 2 , 2 , 2-trifluoroethyl group
  • R 4 represents hydro ⁇ gen atom or methyl group.
  • the compound is selected from the group consisting of:
  • R 1 is hydrogen atom or a C 1 -C4 alkoxy group
  • R 2 and R 3 represent 2 , 2 , 2-trifluoroethyl group
  • R 4 represents hydro ⁇ gen atom.
  • the compound is selected from the group consisting of:
  • R 1 represents hydrogen atom or a C 1 -C2 alkoxy group
  • R 2 and R 3 represent 2 , 2 , 2-trifluoroethyl group
  • R 4 represents hydrogen atom
  • the compound is 2-amino-9- [2- [bis (2, 2, 2- trifluoroethyl ) phosphonylmethoxy] ethyl] -6-phenylthiopurine, 2- amino-9- [2- [bis (2, 2, 2-trifluoroethyl) phosphonylmethoxy] ethyl] -6- p-methoxyphenylthiopurine, 2-amino-9- [2- [bis (2,2,2- trifluoroethyl ) phosphonylmethoxy] ethyl ] - 6-m- methoxyphenylthiopurine, 2-amino-9- [2- [bis (2,2,2- trifluoroethyl ) phosphonylmethoxy] ethyl ] - 6-o- methoxyphenylthiopurine, or 2-amino-9- [2- [bis (2, 2, 2- trifluoroethyl ) phosphonylmethoxy] e
  • Ri is selected from H or methyl
  • each R 2 is independently selected from -R 3 or -OR 3 ;
  • each R 3 is independently selected from Ci-Cs alkyl, or C3-
  • the two R 2 are same; or wherein the two R 2 are differ ⁇ ent .
  • acyclic nucleoside phosphonate derivative or a pharmaceutically acceptable salt, isomer, hydrate or solvate thereof having any one or more of the following:
  • R 2 is -R 3 ;
  • R 2 is -OR3;
  • one R 2 is -R 3 , and the other R 2 is -OR 3 .
  • each R 3 for each occurrence is independently selected from C 1 -C6 alkyl or C3-C 6 cycloalkyl ; preferably, each R 3 for each occurrence is independently selected from C 2 -C6 alkyl or C 4 - C6 cycloalkyl.
  • each R 3 for each occurrence is independently selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert- butyl, t-butyl, n-pentyl, isopentyl, neopentyl, cyclopropyl, cy- clobutyl, cyclopentyl, cyclohexyl, or -CH (CH 2 CH 3 ) 2 , etc.; prefer ⁇ ably, each R 3 for each occurrence is independently selected from ethyl, propyl, isopropyl, butyl, isobutyl, isopentyl, neopentyl, cyclopentyl, cyclohexyl, or -CH (CH 2 CH 3 ) 2 , etc.
  • the acyclic nucleoside phosphonate derivative is se lected from the group consisting of:
  • the acyclic nucleoside phosphonate derivative is se ⁇ lected from the group consisting of:
  • the x related compound' of Alamifovir is se ⁇ lected from compounds which bear one or more structural features in common with Alamifovir, which may point to potential analgesic activity similar to Alamifovir in these compounds.
  • These common structural features which would define a x related com ⁇ pound' of Alamifovir would include the compound being a: a) Purine analogue or derivative, b) Nucleotide analogue, c) Acyclic nucleotide.
  • the compound may be provided in a composition in association with a pharmaceutically acceptable substantially nontoxic carri ⁇ er or excipient.
  • the inventive compound is Emtricitabine (Synonym: (-)-FTC, BW-524W91; Chemical name: (-) - (2R-cis) -4- Amino-5-fluoro-1- [2- (hydroxymethyl ) -1, 3-oxathiolan-5-yl ] -2 (1H) - pyrimidinone / (-)- (2R, 5S) -5-Fluoro-l- [2- (hydroxymethyl) -1, 3- oxathiolan-5-yl ] cytosine / (-) -2 ' , 3 ' -Dideoxy-5-fluoro-3 ' - thiacytidine ; CAS number: 143491-57-0), or any derivatives, salts, prodrugs or metabolites of Emtricitabine, including but not restricted to the salts (-) -Emtricitabine Triphosphate
  • Tetrasodium (CAS number: 1188407-46-6), Emtricitabine 5'- monophosphate, Emtricitabine 5 ' -monophosphate diammonium, (-)- ⁇ - L-2 ' , 3 ' -Dideoxy-5-fluoro-3 ' -thiacytidine-5 ' -diphosphate, (-) - ⁇ - L-2 ' , 3 ' -Dideoxy-5-fluoro-3 ' -thiacytidine-5 ' -diphosphate triammo- nium, (-) -B-L-2 ' , 3 ' -Dideoxy-5-fluoro-3 ' -thiacytidine-5 ' - triphosphate, (-) -B-L-2 ' , 3 ' -Dideoxy-5-fluoro-3 ' -thiacytidine-5 ' - triphosphate tetraammonium, or x related compounds' of Emtricita ⁇ bine
  • Emtricitabine is a pyrimidine nucleoside analogue antivi ⁇ ral compound that was originally developed against Human Immuno ⁇ deficiency Virus (HIV) and Hepatitis B virus infections, and its antiviral properties are effected by the inhibition of the viral reverse transcriptase enzyme (in HIV) and viral DNA polymerase enzyme (in Hepatitis B) .
  • the derivative or salt or prodrug or metab ⁇ olite of Emtricitabine is selected from the compounds as de ⁇ scribed in EP 0513200 B2 or EP 1439177 Bl (all incorporated herein by reference) , especially selected from the compounds, or intermediates thereof , of the formula:
  • R is selected from the group consisting of hydrogen, alkyl, silyl, and acyl
  • Y is selected from the group consisting of hydrogen, methyl, chloro, fluoro, iodo, bromo, alkyl, alkenyl, alkynyl, hydroxyalkyl , carboxyalkyl , thioalkyl, selenoalkyl, phenyl, cy- cloalkyl, cycloalkenyl , thioaryl, and selenoaryl.
  • the compound is 2-hydroxymethyl-5-oxol-l , 3- oxathiolane, 2-acyloxymethyl-5-acyloxy-l , 3-oxathiolane, 2- acetoxymethyl-5-acetoxy-l , 3-oxathiolane .
  • nucleoside having the formula:
  • R is selected from the group consisting of hydro ⁇ gen, alkyl, silyl, and acyl;
  • Y is selected from the group consisting of chloro, bromo, fluoro, and iodo;
  • R is selected from the group consisting of hydro ⁇ gen, alkyl, silyl, and acyl, and wherein Y is fluorine;
  • R is selected from the group consisting of alkyl, silyl, and acyl
  • Y is selected from the group con ⁇ sisting of chloro, bromo, fluoro, and iodo
  • the said derivative or salt or prodrug or metabo ⁇ lite of Emtricitabine is selected from the compounds, or their salts or hydrates or solvates or intermediates thereof, corre ⁇ sponding to the ( - ) -enantiomer of cis-4-ammo-5-fluoro-1- (2- hydroxymethyl-1 , 3-oxathiolane-5-yl ) - (1H) -pyrimidin-2-one, or its pharmaceutically acceptable salt or the 5'-0-alkyl derivative, a 5 ' -O-alkylC (0) derivative, a monophosphate, a diphosphate, or a triphosphate of the ( - ) -enantiomer of cis-4-ammo-5-fluoro-1- (2-hydroxymethyl-l , 3-oxathiolane-5-yl ) - (1H) -pyrimidin-2-one .
  • the x related compound' of Emtricitabine is selected from compounds which bear one or more structural fea ⁇ tures in common with Emtricitabine, which may point to potential analgesic activity similar to Emtricitabine in these compounds.
  • These common structural features which would define a x related compound' of Emtricitabine would include the compound being a: a) Pyrimidine analogue or derivative or b) Nucleoside analogue.
  • the compound may be provided in a composition in association with a pharmaceutically acceptable substantially nontoxic carri ⁇ er or excipient.
  • the inventive compound is Entecavir (Syno ⁇ nym: BMS-200475, ETV, SQ-34676; Chemical name: 2-Amino-9- [ (IS, 3R, 4S) -4-hydroxy-3- (hydroxymethyl ) -2- methylidenecyclopentyl ] -6, 9-dihydro-3H-purin- 6-one /
  • Entecavir tosylate Entecavir toluene sulfonic acid, Entecavir toluene sulfonic acid hydrate, Entecavir (IS) -champhor-10- sulfonate, Entecavir (IS) -champhor-10-sulfonate hydrate,
  • Entecavir p-toluenesulfonate Entecavir p-toluenesulfonate hy ⁇ drate and the Entecavir intermediates (ls-trans) -2-
  • Entecavir is a purine nucleoside analogue antiviral compound with a pentose ring moiety, that was originally developed
  • HSV Herpes Simplex Virus
  • HSV Hepatitis B virus infec ⁇ tions
  • its antiviral properties are effected by the inhibi ⁇ tion of the respective viral DNA polymerase enzymes.
  • the derivative or salt or prodrug or metab ⁇ olite of Entecavir is selected from the compounds as described in EP 0481754 Bl or US 20100210669 Al (all incorporated herein by reference) , especially selected from the compounds, or inter ⁇ mediates thereof, of the formula:
  • R2 is fluoro, chloro, bromo, iodo, hydrogen, methyl, trifluorome- thyl, ethyl, n-propyl, 2-fluoroethyl, 2-chloroethyl, ethynyl or
  • R3 is chloro, bromo, iodo, hydrogen, methyl or trifluoromethyl ;
  • R4 is alkyl;
  • R5 is hydrogen, alkyl, substituted alkyl, or aryl
  • R6 and R7 are independently hydrogen, -PO 3 H 2 , or
  • the said derivative or salt or prodrug or metab ⁇ olite of Entecavir refers to the crystalline form of entecavir having the following general formula (I) :
  • the x related compound' of Entecavir is se ⁇ lected from compounds which bear one or more structural features in common with Entecavir, which may point to potential analgesic activity similar to Entecavir in these compounds.
  • These common structural features which would define a x related compound' of Entecavir would include the compound being a: a) Purine analogue or derivative, b) Pentose ring containing molecule, c) Nucleo ⁇ side analogue.
  • the compound may be provided in a composition in association with a pharmaceutically acceptable substantially nontoxic carri ⁇ er or excipient.
  • the inventive compound is Famciclovir (Syn ⁇ onym: AK-120, BRL-42810, M-5210; Chemical name: 9- [ 4-Acetoxy-3- (acetoxymethyl) butyl] -2-aminopurine; CAS number: 104227-87-4), or any analogues, derivatives, salts, prodrugs, bioprecursors or metabolites of Famciclovir including but not restricted to the salts Famciclovir monohydrate or any phosphate ester and/or acyl derivatives of Famciclovir, or its metabolic active princi- pie compound Penciclovir (Synonym: BRL-39123; Chemical name: 9- [4-Hydroxy-3- (hydroxymethyl) butyl] guanine; CAS number: 39809-25- l),or any analogues, derivatives, salts, prodrugs, bioprecursors or metabolites of Penciclovir, including
  • Famciclovir and Penciclovir are purine nucleoside analogue antiviral compounds, that were originally developed against Her ⁇ pes Simplex Virus (HSV) and Varicella Zoster Virus (VZV) infec ⁇ tions, and their antiviral properties are effected by the inhi ⁇ bition of the respective viral DNA polymerase enzymes.
  • HSV Her ⁇ pes Simplex Virus
  • VZV Varicella Zoster Virus
  • the analogue or derivative or salt or prodrug or bioprecursor or metabolite of Famciclovir is selected from the compounds as described in US 5246937 A and EP 0302644 Bl (incorporated herein by reference) , especially selected from the compounds, or intermediates thereof , of the formula:
  • Ri and R2 are each independently hydrogen, or a carboxylic acyl provided that Ri and R2 are not both hydrogen; or Riand R2 are joined to ⁇ gether to form a cyclic acetal group or a cyclic carbonate group .
  • Ri and/or R2 is a carboxylic acyl group such that the group RiO- and/or R2O- is a pharmaceutically acceptable ester group .
  • carboxylic acyl group Ri and/or R2 is a group o
  • R3 is Ci-6 alkyl, Ci-6 alkoxy or aryl optionally substitut ⁇ ed with one or two groups selected from Ci-6 alkyl, Ci-6 alkoxy and halo.
  • Ri and R2 are joined together to form a group ⁇
  • Ri and R2 are joined together as a 0((3 ⁇ 4)2 group.
  • the compound is selected from:

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Abstract

La présente invention concerne de nouvelles thérapies pour traiter la douleur et des maladies apparentées, ainsi que des composés pharmaceutiques destinés à être utilisés dans lesdites thérapies.
PCT/EP2013/059752 2012-05-11 2013-05-10 Utilisation de composés pour le traitement de la douleur WO2013167743A1 (fr)

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US9908908B2 (en) 2012-08-30 2018-03-06 Jiangsu Hansoh Pharmaceutical Co., Ltd. Tenofovir prodrug and pharmaceutical uses thereof
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WO2018190713A1 (fr) * 2017-04-12 2018-10-18 Umc Utrecht Holding B.V. Inhibiteurs de lysine méthyltransférase destinés au traitement de la douleur
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US11149284B2 (en) 2017-09-26 2021-10-19 Mgenplus Co., Ltd. Transgenic cloned piglet expressing human proinsulin and method of producing the same
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Citations (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0152316B1 (fr) 1984-01-26 1989-07-26 Merck & Co. Inc. Butylguanines substituées et leur utilisation dans des compositions antivirales
EP0141927B1 (fr) 1983-08-18 1991-10-30 Beecham Group Plc Dérivés de guanine antiviraux
US5142051A (en) 1986-07-18 1992-08-25 Ceskoslovenska Akademie Ved N-phosphonylmethoxyalkyl derivatives of pyrimidine and purine bases and a therapeutical composition therefrom with antiviral activity
US5246937A (en) 1985-09-18 1993-09-21 Beecham Group P.L.C. Purine derivatives
EP0388049B1 (fr) 1989-03-03 1995-05-17 Beecham Group Plc Dérivés de penciclovir pour le traitement d'infections de l'Hépatite-B
EP0302644B1 (fr) 1987-08-01 1997-01-29 Beecham Group Plc Dérivés de purine et leur préparation
EP0481754B1 (fr) 1990-10-18 1997-08-20 E.R. Squibb & Sons, Inc. Hydroxymethyl(methylènecyclopentyl)Purines et Pyrimidines
US5663159A (en) 1990-09-14 1997-09-02 Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic Prodrugs of phosphonates
EP0513200B1 (fr) 1990-02-01 1998-09-09 Emory University Procede et compositions de synthese de bch-189 et de composes apparentes
US5866581A (en) * 1993-10-05 1999-02-02 Smithkline Beecham P.L.C. Penciclovir for the treatment of post therapeutic neuralgia
US5922695A (en) 1996-07-26 1999-07-13 Gilead Sciences, Inc. Antiviral phosphonomethyoxy nucleotide analogs having increased oral bioavarilability
US5935946A (en) 1997-07-25 1999-08-10 Gilead Sciences, Inc. Nucleotide analog composition and synthesis method
EP0785208B1 (fr) 1996-01-18 2001-03-21 Mitsubishi Chemical Corporation Composés phosphoniques de nucléotides
EP1049666B1 (fr) 1998-01-23 2003-06-04 Bayer Aktiengesellschaft Nouveaux sulfamides a substitution par naphtyle et anilide
US20050201998A1 (en) * 2003-11-06 2005-09-15 Welch Martha G. Novel multipeptide regimen for the treatment of autistic spectrum, behavioral, emotional and visceral inflammation/autoimmune disorders
US20070196458A1 (en) * 2004-06-07 2007-08-23 Jie Zhang Compositions and methods for dermally treating neuropathic pain
WO2008112715A2 (fr) * 2007-03-12 2008-09-18 Vm Discovery Inc. Nouveaux agents modulateurs des canaux d'ions calcium
EP1439177B1 (fr) 1991-02-22 2010-05-26 Emory University Activité antivirale et résolution de 2-hydroxyméthyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane
US20100210669A1 (en) 2007-02-14 2010-08-19 Weidong Ye Crystalline form of entecavir, its preparation and the pharmaceutical composition and uses thereof
CN101856322A (zh) * 2010-06-11 2010-10-13 中国人民解放军军事医学科学院卫生装备研究所 一种磺胺嘧啶银控释凝胶及制备方法
CN102048677A (zh) * 2009-11-09 2011-05-11 杭州赛利药物研究所有限公司 一种盐酸缬更昔洛韦固体制剂及其制备方法
WO2012062925A2 (fr) * 2010-11-11 2012-05-18 Akron Molecules Gmbh Composés et procédés de traitement de la douleur
EP2511281A1 (fr) 2009-12-10 2012-10-17 Institute Of Pharmacology And Toxicology Academy Of Military Medical Sciences P.L.A. China Dérivé de nucléoside phosphonate acyclique et son utilisation médicale

Patent Citations (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0141927B1 (fr) 1983-08-18 1991-10-30 Beecham Group Plc Dérivés de guanine antiviraux
EP0152316B1 (fr) 1984-01-26 1989-07-26 Merck & Co. Inc. Butylguanines substituées et leur utilisation dans des compositions antivirales
US5246937A (en) 1985-09-18 1993-09-21 Beecham Group P.L.C. Purine derivatives
US5142051A (en) 1986-07-18 1992-08-25 Ceskoslovenska Akademie Ved N-phosphonylmethoxyalkyl derivatives of pyrimidine and purine bases and a therapeutical composition therefrom with antiviral activity
EP0302644B1 (fr) 1987-08-01 1997-01-29 Beecham Group Plc Dérivés de purine et leur préparation
EP0388049B1 (fr) 1989-03-03 1995-05-17 Beecham Group Plc Dérivés de penciclovir pour le traitement d'infections de l'Hépatite-B
EP0513200B1 (fr) 1990-02-01 1998-09-09 Emory University Procede et compositions de synthese de bch-189 et de composes apparentes
US5663159A (en) 1990-09-14 1997-09-02 Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic Prodrugs of phosphonates
EP0481754B1 (fr) 1990-10-18 1997-08-20 E.R. Squibb & Sons, Inc. Hydroxymethyl(methylènecyclopentyl)Purines et Pyrimidines
EP1439177B1 (fr) 1991-02-22 2010-05-26 Emory University Activité antivirale et résolution de 2-hydroxyméthyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane
US5866581A (en) * 1993-10-05 1999-02-02 Smithkline Beecham P.L.C. Penciclovir for the treatment of post therapeutic neuralgia
EP0785208B1 (fr) 1996-01-18 2001-03-21 Mitsubishi Chemical Corporation Composés phosphoniques de nucléotides
US5977089A (en) 1996-07-26 1999-11-02 Gilead Sciences, Inc. Antiviral phosphonomethoxy nucleotide analogs having increased oral bioavailability
US5922695A (en) 1996-07-26 1999-07-13 Gilead Sciences, Inc. Antiviral phosphonomethyoxy nucleotide analogs having increased oral bioavarilability
US5935946A (en) 1997-07-25 1999-08-10 Gilead Sciences, Inc. Nucleotide analog composition and synthesis method
EP1049666B1 (fr) 1998-01-23 2003-06-04 Bayer Aktiengesellschaft Nouveaux sulfamides a substitution par naphtyle et anilide
US20050201998A1 (en) * 2003-11-06 2005-09-15 Welch Martha G. Novel multipeptide regimen for the treatment of autistic spectrum, behavioral, emotional and visceral inflammation/autoimmune disorders
US20070196458A1 (en) * 2004-06-07 2007-08-23 Jie Zhang Compositions and methods for dermally treating neuropathic pain
US20100210669A1 (en) 2007-02-14 2010-08-19 Weidong Ye Crystalline form of entecavir, its preparation and the pharmaceutical composition and uses thereof
WO2008112715A2 (fr) * 2007-03-12 2008-09-18 Vm Discovery Inc. Nouveaux agents modulateurs des canaux d'ions calcium
CN102048677A (zh) * 2009-11-09 2011-05-11 杭州赛利药物研究所有限公司 一种盐酸缬更昔洛韦固体制剂及其制备方法
EP2511281A1 (fr) 2009-12-10 2012-10-17 Institute Of Pharmacology And Toxicology Academy Of Military Medical Sciences P.L.A. China Dérivé de nucléoside phosphonate acyclique et son utilisation médicale
CN101856322A (zh) * 2010-06-11 2010-10-13 中国人民解放军军事医学科学院卫生装备研究所 一种磺胺嘧啶银控释凝胶及制备方法
WO2012062925A2 (fr) * 2010-11-11 2012-05-18 Akron Molecules Gmbh Composés et procédés de traitement de la douleur

Non-Patent Citations (25)

* Cited by examiner, † Cited by third party
Title
1992, PAIN, vol. 48, pages 73 - 81
ANN RHEUM DIS, vol. 67, 2008, pages 1505 - 1515
AREZZO, J.C.; ROSENSTOCK, J.; LAMOREAUX, L.; PAUER, L.: "Efficacy and safetyof pregabalin 600 mg/d for treating painful diabetic peripheral neuropathy: a double-blind placebo- controlled trial", BMC NEUROLOGY, vol. 16, no. 8, 2008, pages 33
BENNETT G.J.; XIE Y.K., PAIN, vol. 33, 1988, pages 87 - 107
BENNETT GJ; CHUNG JM; HONORE M; SELTZER Z.: "Curr Protoc Pharmacol.", July 2003
BLACKBURN-MUNRO G; ERICHSEN H.K., CURRENT PHARM DES, vol. 11, 2005, pages 2961 - 2975
BOYCE-RUSTAY J M ET AL: "Characterization of Fasudil in Preclinical Models of Pain", JOURNAL OF PAIN, SAUNDERS, PHILADELPHIA, PA, US, vol. 11, no. 10, October 2010 (2010-10-01), pages 941 - 949, XP027313509, ISSN: 1526-5900, [retrieved on 20100924] *
BRIDGES, D.; THOMPSON, S.W.; RICE, A.S.: "Mechanisms of neuropathic pain", BR J ANAESTH, vol. 87, no. 1, 2001, pages 12 - 26, XP001068882, DOI: doi:10.1093/bja/87.1.12
CHAPLAN, S.R.; BACH, F.W.; POGREL, J.W.; CHUNG, J.M.; YAKSH, T.L.: "Quantitative assessment of tactile allodynia in the rat paw", J NEUROSCI METHODS, vol. 53, no. 1, 1994, pages 55 - 63, XP024352718, DOI: doi:10.1016/0165-0270(94)90144-9
DA SILVA FILHO A.A.; ANDRADE E SILVA M.L.; CARVALHO J.C.; BASTOS J.K.: "Evaluation of analgesic and anti-inflammatory activities of Nectandra megapotamica (Lauraceae) in mice and rats", J PHARM PHARMACOL., vol. 56, no. 9, 2004, pages 1179 - 84
DRIESSEN B ET AL: "Antinociceptive effect of intrathecally administered P2-purinoceptor antagonists in rats", BRAIN RESEARCH, ELSEVIER, AMSTERDAM, NL, vol. 666, no. 2, 15 December 1994 (1994-12-15), pages 182 - 188, XP024282065, ISSN: 0006-8993, [retrieved on 19941215], DOI: 10.1016/0006-8993(94)90770-6 *
HSIEH, G.C; CHANDRAN, P; SALYERS, A.K; PAI, M; ZHU, C.Z; WENSINK, E.J; WITTE, D.G; MILLER, T.R; MIKUSA, J.P; BAKER, S.J., PHARMACOL BIOCHEM BEHAV, vol. 95, 2010, pages 41 - 50
JETT, M.F.; RAMESHA, C.S.; BROWN, C.D.; CHIU, S.; EMMETT, C.; VORONIN, T.; SUN, T.; O'YANG, C.; HUNTER, J.C.; EGLEN, R.M.: "Characterization of the analgesic and anti-inflammatory activities of ketorolac and its enantiomers in the rat", J PHARMACOL EXP THER, vol. 288, no. 3, 1999, pages 1288 - 97
KIM KJ; YOON YW; CHUNG JM., EXP BRAIN RES., vol. 113, no. 2, February 1997 (1997-02-01), pages 200 - 6
KIM SH; CHUNG JM., PAIN, vol. 50, no. 3, 1992, pages 355 - 63
KONTINEN V.K.; MEERT T.F.: "Prog in Pain Res Management", vol. 24, 2003, IASP PRESS, pages: 489 - 498
LABUDA, C.J.; LITTLE, P., J NEUROSCI METHS, vol. 144, 2005, pages 175 - 181
LALEZARI JACOB ET AL: "A randomized, double-blind, placebo-controlled trial of cidofovir gel for the treatment of acyclovir-unresponsive mucocutaneous herpes simplex virus infection in patients with AIDS", JOURNAL OF INFECTIOUS DISEASES, vol. 176, no. 4, 1997, pages 892 - 898, XP002711213, ISSN: 0022-1899 *
MEOTTI, F.C.; MISSAU, F.C.; FERREIRA, J.; PIZZOLATTI, M.G.; MI- ZUZAKI, C.; NOGUEIRA, C.W.; SANTOS, A.R.S., BIOCHEM PHARMACOL, vol. 72, 2006, pages 1707 - 17134
MILLAN, M.J.; CZLONKOWSKI, A.; MORRIS, B.; STEIN, C.; ARENDT, R.; HUBER, A. ET AL., PAIN, vol. 35, 1988, pages 299 - 312
PETER HYCKEL ET AL: "The therapy of virus-associated epithelial tumors of the face and the lips in organ transplant recipients", MEDICAL MICROBIOLOGY AND IMMUNOLOGY, vol. 192, no. 3, August 2003 (2003-08-01), pages 171 - 176, XP055074902, ISSN: 0300-8584, DOI: 10.1007/s00430-003-0177-y *
SCHAFERS, M.; MARZINIAK, M.; SORKIN, L.S.; YAKSH, T.L.; SOMMER C., EXP NEUROL ., vol. 185, 2004, pages 160 - 168
STATON, P.C.; WILSON, A.W.; BOUNTRA, C.; CHESSELL, I.P.; DAY, N.C., EUR J PAIN, vol. 11, 2007, pages 283 - 289
TAKAHASHI M.; KAWAGUCHI, M.; SHIMADA, K.; KONISHI, N.; FURUYA H.; NAKASHIMA, T., NEUROSCI LETTS, vol. 356, 2004, pages 37 - 40
WHITESIDE, G.T.; ADEDOYIN, A.; LEVENTHAL, L., NEURO- PHARMACOLOGY, vol. 54, 2008, pages 767 - 775

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