WO1993012124A1 - Benzimidazoles substitues et procede de preparation et d'utilisation de ces derniers - Google Patents

Benzimidazoles substitues et procede de preparation et d'utilisation de ces derniers Download PDF

Info

Publication number
WO1993012124A1
WO1993012124A1 PCT/SE1992/000844 SE9200844W WO9312124A1 WO 1993012124 A1 WO1993012124 A1 WO 1993012124A1 SE 9200844 W SE9200844 W SE 9200844W WO 9312124 A1 WO9312124 A1 WO 9312124A1
Authority
WO
WIPO (PCT)
Prior art keywords
methyl
compound
formula
sulfinyl
pyridinyl
Prior art date
Application number
PCT/SE1992/000844
Other languages
English (en)
Inventor
Karl Björn Christer HOLSTEIN
Gunnel Elisabeth Sunden
Original Assignee
Ab Astra
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 Ab Astra filed Critical Ab Astra
Priority to EP93900477A priority Critical patent/EP0628049A1/fr
Priority to SK735-94A priority patent/SK73594A3/sk
Priority to JP5510832A priority patent/JPH07502503A/ja
Priority to KR1019940702131A priority patent/KR940703840A/ko
Priority to AU31752/93A priority patent/AU665043B2/en
Publication of WO1993012124A1 publication Critical patent/WO1993012124A1/fr
Priority to NO942230A priority patent/NO942230D0/no
Priority to FI942912A priority patent/FI942912A/fi

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom

Definitions

  • the object of the present invention is to provide novel compounds, which inhibit exogenously or endogenously stimulated gastric acid secretion and thus can be used in the prevention and treatment of peptic ulcer.
  • the present invention also relates to the use of the compounds of the invention for inhibiting gastric acid secretion in mammals including man.
  • the compounds of the invention may be used for prevention and treatment of gastrointestinal
  • the compounds may be used for treatment of other gastrointestinal disorders where gastric antisecretory effect is
  • the compounds of the invention may also be used for treatment or prophylaxis of inflammatory conditions in mammals, including man, especially those involving lysozymal enzymes .
  • the invention also relates to pharmaceutical compositions containing the compounds of the invention, as active ingredient.
  • the invention relates to processes for preparation of such new compounds and to the use of the active compounds for the preparation of pharmaceutical compositions for the medical use indicated above.
  • the compounds of the invention will not block the uptake of iodine into the thyroid gland. It has earlie been disclosed in several lectures from the company, where the inventors are working that thyroid toxicity depends on if the compounds are lipophilic or not. The inventors have now unexpectedly found that it is not the lipophilicity that is the critical parameter.
  • the claimed compounds which include rather hydrophilic compounds, do not give any thyroid toxic effect and have at the same time high acid secretion inhibitory effect.
  • the compounds of the invention will also exhibit a high solubility and a high chemical stability in water.
  • the compounds of the invention exhibit a high solubility and a high chemical stability in water.
  • the compounds of the invention are therefore
  • administration routes such as for instance oral and rectal administration.
  • R 1 and R 2 which are different, is each methyl, -C(O)-
  • the structural isomers of the compounds of the formula I may be used separately, or in equal or unequal mixtures.
  • the compounds of the invention of the formula I have an asymmetric centre in the sulfur atom, i.e. exists as two optical isomers (enantiomers). Both the pure enantiomers, racemic mixtures (50% of each enantiomer) and unequal mixtures of the two are within the scope of the present invention.
  • the compounds of the invention may be prepared
  • Z is halogen such as CI, Br or I or a functionally equivalent group, with a compound of the formula III
  • Q is a counter ion such as Na + , K + , Ag + or trialkylammonium.
  • Salts obtained may be transformed to a therapeutically suitable salt such as sodium and potassium salts, by addition of NaOH and KOH, respectively or by ion exchange.
  • a therapeutically suitable salt such as sodium and potassium salts, by addition of NaOH and KOH, respectively or by ion exchange.
  • This oxidation may be carried out by using an oxidizing agent such as nitric acid, hydrogen peroxide,
  • the oxidation may also be carried out enzymatically by using an oxidizing enzyme or microbiotically by using a suitable microorganism.
  • the structural isomers obtained may be separated by means of crystallization or chromatography.
  • Racemates obtained can be separated according to known methods, e.g. recrystallization from an optically active solvent.
  • the compounds of the invention are formulated into pharmaceutical formulations for oral, rectal, parenteral or other mode of administration. It is especially preferred to formulate the compounds of the invention into pharmaceutical formulations for parenteral administration.
  • formulation contains a compound of the invention in combination with a pharmaceutically acceptable carrier.
  • the carrier may be in the form of a solid, semi-solid or liquid diluent, or a capsule.
  • the amount of active compounds is between 0.1- 95% by weight of the preparation, between 0.2-20% by weight in preparations for parenteral use and between 1 and 50% by weight in preparations for oral
  • the compound selected may be mixed with a solid, powdered carrier, such as lactose, saccharose, sorbitol, mannitol, starch, amylopectin, cellulose derivatives, gelatin, or another suitable carrier, as well as with lubricating agents such as magnesium stearate, calcium stearate, sodium stearyl fumarate and polyethylenglycol waxes.
  • a solid, powdered carrier such as lactose, saccharose, sorbitol, mannitol, starch, amylopectin, cellulose derivatives, gelatin, or another suitable carrier, as well as with lubricating agents such as magnesium stearate, calcium stearate, sodium stearyl fumarate and polyethylenglycol waxes.
  • lubricating agents such as magnesium stearate, calcium stearate, sodium stearyl fumarate and polyethylenglycol waxes.
  • sulfoxides may be coated with an enteric coating, which protects the active compound from acid catalyzed degradation as long as the dosage form remains in the stomach.
  • enteric coating is chosen among
  • enteric-coating materials e.g. beeswax, shellac or anionic film-forming polymers such as cellulose acetate phtalate, hydroxypropyl- methylcellulose phthalate, partly methyl esterified methacrylic acid polymers and the like, if preferred in combination with a suitable plasticizer.
  • enteric-coating materials e.g. beeswax, shellac or anionic film-forming polymers such as cellulose acetate phtalate, hydroxypropyl- methylcellulose phthalate, partly methyl esterified methacrylic acid polymers and the like, if preferred in combination with a suitable plasticizer.
  • enteric-coating materials e.g. beeswax, shellac or anionic film-forming polymers such as cellulose acetate phtalate, hydroxypropyl- methylcellulose phthalate, partly methyl esterified methacrylic acid polymers and the like, if preferred in combination with a suitable plastic
  • Soft gelatine capsules may be prepared with capsules containing a mixture of the active compound or
  • Hard gelatine capsules may also be enteric-coated as described above.
  • Hard gelatine capsules may contain granules or enteric-coated granules of the active compound.
  • Hard gelatine capsules may also contain the active compound in combination with a solid powdered carrier such as lactose, saccharose, sorbitol,
  • Dosage units for rectal administration may be prepared in the form of suppositories which contain the active substance mixed with a neutral fat base, or they may be prepared in the form of a gelatine rectal capsule which contains the active substance in a mixture with a vegetable oil, paraffin oil or other suitable vehicle for gelatine rectal capsules, or they may be prepared in the form of a ready-made micro enema, or they may be prepared in the form of a dry micro enema formulation to be reconstituted in a suitable solvent just prior to administration.
  • Liquid preparation for oral administration may be prepared in the form of syrups or suspensions, e.g.
  • solutions or suspensions containing from 0.2% to 20% by weight of the active ingredient and the remainder consisting of sugar or sugar alcohols and a mixture of ethanol, water, glycerol, propylene glycol and
  • compositions may contain colouring agents, flavouring agents, saccharine and carboxymethyl cellulose or other thickening agents.
  • Liquid preparations for oral may contain colouring agents, flavouring agents, saccharine and carboxymethyl cellulose or other thickening agents.
  • administration may also be prepared in the form of a dry powder to be reconstituted with a suitable solvent prior to use.
  • Solutions for parenteral administration may be prepared as a solution of a compound of the invention in a pharmaceutically acceptable solvent, preferably in a concentration from 0.1% to 10% by weight.
  • solutions may also contain stabilizing agents and/or buffering agents and may be manufactured in different unit dose ampoules or vials. Solutions for parenteral administration may also be prepared as a dry
  • the typical daily dose of the active substance varies within a wide range and will depend on various factors such as for example the individual requirement of each patient, the route of administration and the disease. In general, oral and parenteral dosages will be in the range of 5 to 500 mg per day of active substance.
  • Example 1 Preparation of phosphoric acid, [5-acetyl- 6-methyl-2-[[(3,4-dimethoxy-2- pyridinyl)methyl]sulfinyl]-1H-benzimidazole-1-yl]methyl ester, disodium salt or phosphoric acid, [6-acetyl-5- methyl-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]sulfinyl]- 1H-benzimidazole-1-yl]methyl ester, disodium salt.
  • Tributylamine (1.7 ml, 7.0 mmol) was added with stirring to a solution of phosphoric acid, 85 per cent (0.24 ml, 3.6 mmol) in ethanol (2 ml). The solvent was evaporated and the residue taken up in methylene chloride (2.5 ml). The organic phase was dried over sodium sulphate, filtered and evaporated.
  • Example 2 Preparation of phosphoric acid, [5-carbo methoxy-6-methyl-2-[[(3,4-dimethoxy-2- pyridinyl)methyl]sulfinyl]-1H-benzimidazole-1-yl]methyl ester, disodium salt or phosphoric acid, [6- carbomethoxy-5-methyl-2-[[(3,4-dimethoxy-2- pyridinyl)methyl]sulfinyl]-1H-benzimidazole-1-yl]methyl ester, disodium salt.
  • Example I 1 Preparation of 5-acetyl-1-hydroxymethyl-6-methyl-2-[[(3 dimethoxy-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole 6-acetyl-1-hydroxymethyl-5-metyl-2-[[(3,4-dimethoxy-2-p dinyl)methyl]sulfinyl]-1H-benzimidazole To a mixture of 5-acetyl-6-methyl-2-[[(3,4-dimethoxy-2- pyridinyl)methyl]sulfinyl]-1H-benzimidazole (2.00 g,
  • compositions containing a compound of the invention as active ingredient are illustrated in the following formulations.
  • flavouring agents dissolved in ethanol were added. The mixture was diluted with water to a final volume of 100 ml. Enteric-coated tablets
  • a parenteral formulation for intravenous use is provided.
  • the active compound was dissolved in water to a final volume of 1000 ml.
  • the solution was filtered through a 0.22 ⁇ m filter and immediately dispensed into 10 ml sterile ampoules. The ampoules were sealed. Tablets
  • Tablets containing 30 mg of active compound were prepared from the following ingredients: Compound according to Example 3 in Table 3 300 g
  • the active compound was mixed with lactose and part of the PVP-XL and granulated with a solution of methyl cellulose and disodium hydrogen phosphate.
  • the wet mass was forced through a screen and dried in a fluidized bed dryer. After adding magnesium stearate and the remainder in PVP-XL and mixing, the drug mixture was compressed into tablets with a mean weight of 110 mg, each tablet containing 30 mg of the active compound.
  • Suppositories were prepared from the following
  • Each suppository contained 40 mg of active compound.
  • the active compound mixture was homogenously mixed with Witepsol H-15 at a temperature of 41°C.
  • the molten mass was volume filled into pre-fabricated suppository packages to a net weight of 1.84 g. After cooling the packages were heat sealed.
  • Each suppository contained 40 mg of active compound.
  • the active compound dissolved in 10 ml of sterile water is transferred into 100 ml of normal saline solution for infusion to give a total volume of about 110 ml.
  • the solution is administered as an intravenous infusion during a time period of about 30 minutes.
  • a syrup containing 1% of active substance was prepared from the following ingredients:
  • the active compound was dissolved in water to a final volume of 1000 ml.
  • the solution was filtered through a sterile 0.22 ⁇ m filter and aseptically dispensed into 1 ml sterile ampoules. The ampoules were sealed.
  • Sterile compound according to Example 2 60 mg Sterile injection vials and stoppers Sterile active compound, 60 mg, was dispensed into 10 ml sterile injection vials. The vials were stoppered with sterile rubberstoppers. The vokale filling operation was performed under aseptic conditions in a sterile production area under vertical laminar flow.
  • Test substances suspended in 0.5% buffered (pH 9) methocel, were administered by oral gavage in a volume of 5 ml/kg body weight. After 1 hour, 125 I (300kBq/kg,
  • test agent- and placebo- treated animals were assessed with the Mann-Whitney U- test (two-tailed). P ⁇ 0.05 was accepted as significant.
  • Table 4 give the test data available for the compounds of the invention.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Nouveaux composés de la formule (I) dans laquelle R1 et R2, qui sont différents, représentent chacun méthyle, -C(O)-CH¿3? ou -C(O)-OCH3, R?1 ou R2¿ représentant toujours méthyle; et M représente un contre-cation physiologiquement acceptable. L'invention se rapporte à des procédés de préparation desdits composés, à des compositions pharmaceutiques contenant lesdits composés comme principe actif, ainsi qu'à l'utilisation en médecine de ces composés.
PCT/SE1992/000844 1991-12-19 1992-12-08 Benzimidazoles substitues et procede de preparation et d'utilisation de ces derniers WO1993012124A1 (fr)

Priority Applications (7)

Application Number Priority Date Filing Date Title
EP93900477A EP0628049A1 (fr) 1991-12-19 1992-12-08 Benzimidazoles substitues et procede de preparation et d'utilisation de ces derniers
SK735-94A SK73594A3 (en) 1991-12-19 1992-12-08 Substituted benzimidazoles, process for their production as well as their use
JP5510832A JPH07502503A (ja) 1991-12-19 1992-12-08 置換ベンズイミダゾール類，その製造方法およびその使用
KR1019940702131A KR940703840A (ko) 1991-12-19 1992-12-08 치환 벤즈이미다졸, 그의 제조 방법 및 용도(substituted benzimidazoles, process for their preparation as well as their use)
AU31752/93A AU665043B2 (en) 1991-12-19 1992-12-08 Substituted benzimidazoles, process for their preparation as well as their use
NO942230A NO942230D0 (no) 1991-12-19 1994-06-14 Substituerte benzimidazoler, fremgangsmåte for deres fremstilling samt deres anvendelse
FI942912A FI942912A (fi) 1991-12-19 1994-06-17 Substituoidut bentsimidatsolit, menetelmä niiden valmistamiseksi sekä niiden käyttö

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE9103776-2 1991-12-19
SE9103776A SE9103776D0 (sv) 1991-12-19 1991-12-19 New compounds

Publications (1)

Publication Number Publication Date
WO1993012124A1 true WO1993012124A1 (fr) 1993-06-24

Family

ID=20384667

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/SE1992/000844 WO1993012124A1 (fr) 1991-12-19 1992-12-08 Benzimidazoles substitues et procede de preparation et d'utilisation de ces derniers

Country Status (25)

Country Link
EP (1) EP0628049A1 (fr)
JP (1) JPH07502503A (fr)
KR (1) KR940703840A (fr)
CN (1) CN1031827C (fr)
AP (1) AP397A (fr)
AU (1) AU665043B2 (fr)
CA (1) CA2124689A1 (fr)
CZ (1) CZ146794A3 (fr)
FI (1) FI942912A (fr)
HR (1) HRP921400A2 (fr)
HU (1) HUT68270A (fr)
IL (1) IL104025A0 (fr)
IS (2) IS4079A (fr)
MA (1) MA22746A1 (fr)
MX (1) MX9207269A (fr)
NO (1) NO942230D0 (fr)
NZ (1) NZ246220A (fr)
SE (1) SE9103776D0 (fr)
SI (1) SI9200402A (fr)
SK (1) SK73594A3 (fr)
TN (1) TNSN92115A1 (fr)
TW (1) TW224100B (fr)
WO (1) WO1993012124A1 (fr)
YU (1) YU101692A (fr)
ZA (1) ZA928836B (fr)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998020013A1 (fr) * 1996-11-07 1998-05-14 Andreas Johannes Kesel Nouveaux produits de condensation de knoevenagel, leur procede de production et leur utilisation
WO1999033846A2 (fr) * 1997-12-31 1999-07-08 The University Of Kansas Remedes contenant des precurseurs hydrosolubles d'amines secondaires et tertiaires, et leurs procedes d'obtention
US7893271B2 (en) 2005-07-28 2011-02-22 Intervet International B.V. Benzimidazole carbamates and (thio) carbamates, and the synthesis and use thereof
US8188119B2 (en) 2008-10-24 2012-05-29 Eisai R&D Management Co., Ltd Pyridine derivatives substituted with heterocyclic ring and γ-glutamylamino group, and antifungal agents containing same
RU2485131C2 (ru) * 2007-12-27 2013-06-20 Эйсай Ар Энд Ди Менеджмент Ко., Лтд. Производные пиридина, замещенные гетероциклическим кольцом и фосфоноксиметильной группой и содержащие их противогрибковые средства
US8507530B2 (en) 2007-04-27 2013-08-13 Eisai R&D Management Co., Ltd. Pyridine derivatives substituted by heterocyclic ring and phosphonoamino group, and anti-fungal agent containing same
US8777134B2 (en) 2006-06-14 2014-07-15 Intervet International B.V. Suspension comprising benzimidazole carbamate and a polysorbate
US8841327B2 (en) 2005-10-31 2014-09-23 Eisai R&D Management Co., Ltd. Heterocycles substituted pyridine derivatives and antifungal agent containing thereof
WO2016085319A1 (fr) * 2014-11-26 2016-06-02 Universidad Nacional Autonoma De Mexico Nouveaux composés hydrosolubles dérivés du benzimidazole, utiles pour le traitement de la fasciolose

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0279149A2 (fr) * 1986-11-21 1988-08-24 Aktiebolaget Hässle Dérivés du benzimidazole, leur procédé de préparation et compositions pharmaceutiques les contenant
GB2219584A (en) * 1988-05-20 1989-12-13 Haessle Ab Phosphates of benzimidazole-methanols

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE9002206D0 (sv) * 1990-06-20 1990-06-20 Haessle Ab New compounds
ATE184602T1 (de) * 1990-06-20 1999-10-15 Astra Ab Dialkoxypyridinylbenzimidazolderivate, verfahren zur herstellung und ihre pharmazeutische verwendung

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0279149A2 (fr) * 1986-11-21 1988-08-24 Aktiebolaget Hässle Dérivés du benzimidazole, leur procédé de préparation et compositions pharmaceutiques les contenant
GB2219584A (en) * 1988-05-20 1989-12-13 Haessle Ab Phosphates of benzimidazole-methanols

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998020013A1 (fr) * 1996-11-07 1998-05-14 Andreas Johannes Kesel Nouveaux produits de condensation de knoevenagel, leur procede de production et leur utilisation
AU728345B2 (en) * 1996-11-07 2001-01-04 Andreas Johannes Kesel New knoevenagel condensation products, method for their production and their use
WO1999033846A2 (fr) * 1997-12-31 1999-07-08 The University Of Kansas Remedes contenant des precurseurs hydrosolubles d'amines secondaires et tertiaires, et leurs procedes d'obtention
WO1999033846A3 (fr) * 1997-12-31 1999-10-28 Univ Kansas Remedes contenant des precurseurs hydrosolubles d'amines secondaires et tertiaires, et leurs procedes d'obtention
US5985856A (en) * 1997-12-31 1999-11-16 University Of Kansas Water soluble prodrugs of secondary and tertiary amine containing drugs and methods of making thereof
JP2001527083A (ja) * 1997-12-31 2001-12-25 ザ・ユニバーシティ・オブ・カンザス 第二級および第三級アミン含有薬剤の水溶性プロドラッグおよびその製造方法
US7893271B2 (en) 2005-07-28 2011-02-22 Intervet International B.V. Benzimidazole carbamates and (thio) carbamates, and the synthesis and use thereof
US8841327B2 (en) 2005-10-31 2014-09-23 Eisai R&D Management Co., Ltd. Heterocycles substituted pyridine derivatives and antifungal agent containing thereof
US8777134B2 (en) 2006-06-14 2014-07-15 Intervet International B.V. Suspension comprising benzimidazole carbamate and a polysorbate
US8507530B2 (en) 2007-04-27 2013-08-13 Eisai R&D Management Co., Ltd. Pyridine derivatives substituted by heterocyclic ring and phosphonoamino group, and anti-fungal agent containing same
RU2485131C2 (ru) * 2007-12-27 2013-06-20 Эйсай Ар Энд Ди Менеджмент Ко., Лтд. Производные пиридина, замещенные гетероциклическим кольцом и фосфоноксиметильной группой и содержащие их противогрибковые средства
US8513287B2 (en) 2007-12-27 2013-08-20 Eisai R&D Management Co., Ltd. Heterocyclic ring and phosphonoxymethyl group substituted pyridine derivatives and antifungal agent containing same
US8188119B2 (en) 2008-10-24 2012-05-29 Eisai R&D Management Co., Ltd Pyridine derivatives substituted with heterocyclic ring and γ-glutamylamino group, and antifungal agents containing same
WO2016085319A1 (fr) * 2014-11-26 2016-06-02 Universidad Nacional Autonoma De Mexico Nouveaux composés hydrosolubles dérivés du benzimidazole, utiles pour le traitement de la fasciolose
US10239842B2 (en) 2014-11-26 2019-03-26 Universidad Nacional Autonoma De Mexico Hydrosoluble compounds derived from benzimidazole used in treating fasciolosis

Also Published As

Publication number Publication date
NZ246220A (en) 1996-02-27
CN1031827C (zh) 1996-05-22
SE9103776D0 (sv) 1991-12-19
IS3960A (is) 1993-06-20
NO942230L (no) 1994-06-14
AP397A (en) 1995-08-14
NO942230D0 (no) 1994-06-14
HRP921400A2 (en) 1994-08-31
AU3175293A (en) 1993-07-19
CZ146794A3 (en) 1996-02-14
JPH07502503A (ja) 1995-03-16
MX9207269A (es) 1993-06-01
EP0628049A1 (fr) 1994-12-14
CA2124689A1 (fr) 1993-06-24
FI942912A0 (fi) 1994-06-17
TNSN92115A1 (fr) 1993-06-08
AP9200463A0 (en) 1993-01-31
KR940703840A (ko) 1994-12-12
YU101692A (sh) 1995-10-03
CN1073446A (zh) 1993-06-23
ZA928836B (en) 1993-07-05
HU9401840D0 (en) 1994-09-28
AU665043B2 (en) 1995-12-14
IS4079A (is) 1993-06-20
FI942912A (fi) 1994-06-17
IL104025A0 (en) 1993-05-13
SK73594A3 (en) 1995-02-08
SI9200402A (en) 1993-06-30
HUT68270A (en) 1995-06-28
TW224100B (fr) 1994-05-21
MA22746A1 (fr) 1993-07-01

Similar Documents

Publication Publication Date Title
EP0593463B1 (fr) Derives de dialcoxy-pyridinyle-benzimidazole, procede de preparation et utilisation pharmaceutique de ces derives
AP215A (en) Substituted benzimidazoles, process for their preparation and their pharmaceutical use.
AU612129B2 (en) New benzimidazole derivatives a process for production thereof and a pharmaceutical composition containing the same
JPH0739412B2 (ja) 新規なスルホキシド
EP0449940A1 (fr) Nouveau compose therapeutiquement actif et son procede de preparation.
JP2793907B2 (ja) 治療上活性な置換されたベンズイミダゾールおよびその製法
EP0173664A2 (fr) Dérivés de benzimidazole biologiquement actifs et leur procédé de préparation
AP397A (en) Substituted benzimidazoles, process for their preparation as well as their use.
EP0449935B1 (fr) Compose a effet inhibiteur d'acide gastrique et son procede de preparation
GB2219584A (en) Phosphates of benzimidazole-methanols

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AT AU BB BG BR CA CH CS DE DK ES FI GB HU JP KP KR LK LU MG MN MW NL NO NZ PL PT RO RU SD SE UA

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 2124689

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 246220

Country of ref document: NZ

WWE Wipo information: entry into national phase

Ref document number: PV1994-1467

Country of ref document: CZ

Ref document number: 1993900477

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 73594

Country of ref document: SK

WWE Wipo information: entry into national phase

Ref document number: 942912

Country of ref document: FI

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWP Wipo information: published in national office

Ref document number: 1993900477

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: PV1994-1467

Country of ref document: CZ

WWW Wipo information: withdrawn in national office

Ref document number: 1993900477

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: PV1994-1467

Country of ref document: CZ