+

WO1998033778A1 - Derives triazole - Google Patents

Derives triazole Download PDF

Info

Publication number
WO1998033778A1
WO1998033778A1 PCT/JP1998/000449 JP9800449W WO9833778A1 WO 1998033778 A1 WO1998033778 A1 WO 1998033778A1 JP 9800449 W JP9800449 W JP 9800449W WO 9833778 A1 WO9833778 A1 WO 9833778A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
naphthyl
halogen atom
acceptable salt
lower alkyl
Prior art date
Application number
PCT/JP1998/000449
Other languages
English (en)
Japanese (ja)
Inventor
Teruo Tanaka
Sadao Oida
Satoshi Ohya
Original Assignee
Sankyo Company, Limited
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 Sankyo Company, Limited filed Critical Sankyo Company, Limited
Priority to AU57795/98A priority Critical patent/AU5779598A/en
Publication of WO1998033778A1 publication Critical patent/WO1998033778A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles

Definitions

  • the present invention relates to a 1,2,4-triazole compound represented by the formula (I), which is particularly effective for fungal diseases of humans and animals, a pharmacologically acceptable salt thereof, and those as active ingredients.
  • Compositions for the treatment or prevention of fungal diseases, their use in the manufacture of a medicament for the treatment or prevention of fungal diseases, or the administration of a pharmacologically effective amount thereof to a warm-blooded animal The present invention relates to a method for treating or preventing a fungal disease.
  • the present invention is a compound having the formula (I) or a pharmacologically acceptable salt thereof.
  • Ar 1 represents a phenyl group or a phenyl group having 1 to 3 substituents (the substituents represent a halogen atom or a trifluoromethyl group);
  • Ar 2 is naphthyl, an 8 to 10-membered fused bicyclic aromatic heterocyclic group (the fused bicyclic aromatic heterocyclic group has at least one nitrogen, oxygen, or sulfur atom) or 1
  • a naphthyl group having 3 to 3 substituents or a condensed aromatic heterocyclic group (the substituent is a lower alkyl group, a lower alkoxy group, a halogen atom, a lower alkyl group substituted by a halogen atom, a halogen atom A lower alkoxy group, a nitro group, a cyano group, a —S (0) m R 2 group (R 2 : a lower alkyl group optionally substituted with a halogen atom; m: 0, 1 or 2 Or a -
  • R 1 represents a hydrogen atom or a lower alkyl group
  • A represents an aliphatic carbocyclic group having 4 to 7 carbon atoms or a 4- to 7-membered aliphatic heterocyclic group having at least one nitrogen, oxygen or sulfur atom.
  • Examples of the condensed bicyclic aromatic heterocyclic group and the halogen atom of the alkyl group substituted with the halogen atom of R 2 include a fluorine, chlorine or bromine atom.
  • the lower alkyl group of the lower alkyl group for R 3 represents a linear or branched alkyl group having 1 to 6 carbon atoms, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert.
  • a linear or branched alkyl group having 1 to 6 carbon atoms for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert.
  • butyl, pentyl, isopentyl or A xyl group preferably a straight-chain or branched alkyl group having 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, t-butyl. Groups.
  • the lower alkoxy group of the lower alkoxy group of Ar 2 and the naphthyl group having a lower alkoxy group substituted with a halogen atom as a substituent and the lower alkoxy group of the 8- to 10-membered condensed aromatic heterocyclic heterocyclic group have 1 to 1 carbon atoms.
  • the 8- to 10-membered fused bicyclic aromatic heterocyclic group of Ar 2 is, for example, a quinolyl, isoquinolyl, benzofuranyl, benzochenyl, indril, benzimidazolyl, benzoxazozolyl or benzothiazolyl group. No.
  • the aliphatic carbocyclic group consisting of 4 to 7 carbon atoms of A includes, for example, a cyclobutane, cyclopentane, cyclohexane or cycloheptane ring.
  • the 4- to 7-membered aliphatic heterocyclic group having at least one nitrogen, oxygen, and sulfur atom of A is, for example, azetidine, pyrrolidine, piperidine, oxetane, tetrahydrofuran, tetrahydrofuran.
  • Examples include dropyran, chetan, tetrahydrodrathiophene, pentamethylene sulfide, dioxane, dithiane, tetrahydrodroxazine, or tetrathiazine ring.
  • Ar 1 is a phenyl group having 1 to 2 substituents (the substituent is a fluorine atom, a chlorine atom And a trifluoromethyl group) are particularly preferred.
  • Ar 1 is a dichloromouth phenyl, difluorophenyl, chlorophenyl, fluorophenyl, (trifluoromethyl) phenyl or fluoro (trifluoromethyl) phenyl group, and preferably 2,4-dichlorophenyl With enyl, 2,4-difluorophenyl, 4-chlorophenyl, 2-fluorophenyl, 4-fluorophenyl, 4- (trifluoromethyl) phenyl or 2-fluoro-4- (trifluoromethyl) phenyl Yes, particularly preferred are compounds which are 2,4-dichlorophenyl, 2,4-difluorophenyl or 4_ (trifluoromethyl) phenyl group.
  • Ar 2 is naphthyl, an 8- to 10-membered condensed bicyclic aromatic heterocyclic group (the condensed bicyclic aromatic heterocyclic group has at least one nitrogen, oxygen or sulfur atom) or 1 to 3
  • a substituted or unsubstituted naphthyl group or an 8- to 10-membered fused bicyclic aromatic heterocyclic group (the substituent is a lower alkyl group, a halogen atom, a lower alkyl group substituted with a halogen atom, a halogen atom in substituted lower alkoxy group, nitro group, Shiano Motoma others, - S (0) m R 2 group (R 2: a lower alkyl group which may be substituted with a halogen atom; m: 0, 1 or 2 Wherein the fused bicyclic aromatic heterocyclic group has at least one nitrogen, oxygen or sulfur atom).
  • Ar 2 is naphthyl, an 8 to 10-membered fused aromatic heterocyclic group (the fused bicyclic aromatic heterocyclic group has 1 to 2 nitrogen, oxygen or sulfur atoms) or 1 to 3 Or a naphthyl group having 8 substituents or an 8- to 10-membered fused bicyclic aromatic heterocyclic group (the substituent is a lower alkyl group, a halogen atom, a lower alkyl group substituted with a halogen atom, a halogen atom in substituted lower alkoxy group, two collected by filtration group, Shiano group or, - S (0) m R 2 group (R 2: a lower alkyl group which may toying substituted by a halogen atom; m: 0, 1 or 2 And the condensed bicyclic aromatic heterocyclic group has 1 to 2 nitrogen, oxygen or sulfur atoms).
  • Ar 2 is naphthyl, an 8- to 10-membered condensed bicyclic aromatic heterocyclic group (the condensed bicyclic aromatic heterocyclic group has 1 to 2 nitrogen, oxygen or sulfur atoms) or 1 to A naphthyl group having two substituents or an 8- to 10-membered fused bicyclic aromatic heterocyclic group (the substituent is a lower alkyl group, a halogen atom, a lower alkyl group substituted by a halogen atom, substituted lower alkoxy group a halogen atom, two collected by filtration group, Shiano group or, - S (0) m R 2 group (R 2: a lower alkyl group optionally substituted by a halogen atom; m: 0, 1 or 2), wherein the fused bicyclic aromatic heterocyclic group has 1 to 2 nitrogen, oxygen or sulfur atoms).
  • Ar 2 is naphthyl, quinolyl, Lee Sokino Lil, naphthyl having benzofuranyl, Benzoche two Le, Lee down drill Le, the Benzoi imidazolyl, also is properly benzo O hexa benzotriazolyl Benzochia Zoriru group or from 1 to 2 substituents, Quinolyl, isoquinolyl, benzofuranyl, benzochenyl, indolyl, benzoimidazolyl, benzoxazolyl or benzothiazolyl group (the substituent is a lower alkyl group, a halogen atom, a lower alkyl group substituted by a halogen atom) , low grade alkoxy group substituted with a halogen atom, two collected by filtration group, Shiano group or, - S (0) m R 2 group (R 2: a lower alkyl group optionally substituted by a halogen atom; m: 0, A compound which represents
  • Ar 2 is fluoronaphthyl, black naphthyl, bromonaphthyl, bromofluoronaphthyl, difluoronaphthyl, dichloronaphthyl, dibromonaphthyl, (trifluoromethyl) naphthyl, (ditrifluoromethyl) naphthyl , (Trichloromethyl) naphthyl, Fluoro (Trifluoromethyl) Naphthyl, Fluoro (Trifluoromethoxy) Naphthyl, Fluoromethoxy-(Trifluoromethyl) naphthyl, (Difluoromethoxy) Naphthyl, (Trifluoromethoxy) Xy) naphthyl, (2,2,2—trifluoretoxy) naphthyl, (1,1,2,2—tetrafluroletoxy) naphthyl (2,2,3,3—te
  • R 1 is a hydrogen atom, a methyl group, an ethyl group, a propyl group or an isopropyl group.
  • A is an aliphatic carbon group having 4 to 7 carbon atoms or a nitrogen-, oxygen-, or 4- to 7-membered aliphatic heterocyclic group having 1 to 2 sulfur atoms are preferable,
  • A is an aliphatic carbon group having 4 to 6 carbon atoms or a 4 to 6-membered aliphatic heterocyclic group having 1 to 2 nitrogen, oxygen or sulfur atoms.
  • A is cyclobutane, cyclopentane, cyclohexane, cycloheptane, azetidine, pyrrolidine, piperidine, oxetane, tetra Hydrofuran, Tetrahydropyran, Chetan, Tetrahydrothiophene, Pentamethylensulfide, Dioxan, Zithian, Dihydroxazine, Tetrahydroxazine, Dihydrothiazine Or a tetrahydrothiazine ring, preferably cyclobutane, cyclohexane, azetidine, piperidine, tetrahydropyran, dioxane, dithian, tetrahydroxa
  • Me represents methyl
  • Preferred compounds in the above table are 1, 6, 16, 26, 34, 35, 42, 52, 57, 62, 67, 82, 90, 93, 98, 1 15, 12 0, 12 3 and 13 3 are particularly preferred compounds.
  • the triazole compound (I) of the present invention has at least two asymmetric carbons and includes optical isomers and diastereomers.
  • the enantiomers can be obtained as enantiomers by a general optical resolution technique or an asymmetric synthesis technique. Further, diastereomers can be separated by using a usual separation method such as fractional recrystallization or chromatography.
  • the compound (I) of the present invention includes one or a mixture of these isomers.
  • the triazole compound (I) of the present invention can be used as an antifungal agent as it is or in the form of a pharmacologically acceptable salt.
  • Pharmaceutically acceptable salts of compound (I) include, for example, salts of inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, acetic acid, fumaric acid, maleic acid, oxalic acid, malonic acid, succinic acid Salts of carboxylic acids such as acetic acid, citric acid, and linoleic acid; salts of sulfonic acids such as methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, and toluenesulfonic acid; or amino acids such as glutamic acid and aspartic acid. It is a salt, preferably a salt of a carboxylic acid.
  • the hydrate of the compound (I) and the hydrate of the salt of the compound (I) are also
  • the compound (I) of the present invention and a pharmaceutically acceptable salt thereof exhibit excellent antifungal activity.
  • the compound (I) and a pharmaceutically acceptable salt thereof are used as an antifungal agent.
  • excipients eg, lactose, sucrose, glucose, saccharides such as mannite, sorbitol; corn starch, potato starch, ⁇ -starch, dextrin, carboxymethyl starch.
  • Such starch derivatives such as crystalline cellulose, low-substituted hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxymethylcellulose calcium, and internally cross-linked carboxymethylcellulose sodium.
  • carbonate derivatives eg. the above-mentioned excipients; gelatin; polybulpyridone; magrogol; etc.
  • disintegrants eg, the aforementioned Excipients; chemically modified starches, cellulose derivatives, etc., such as skull carmellonium sodium, carboxymethyl starch sodium, cross-linked polyvinylpyrrolidone, and lubricants (eg, Talc; stearic acid;
  • the lower limit 1 mg per (preferably, 5 mg), the upper 2 0 0 0 m g (preferably, 1 0
  • the lower limit should be 0.1 mg (preferably 0.5 mg) and the upper limit should be 600 tng (preferably 500 mg) per adult. It is desirable to administer 1 to 6 times a day depending on the symptoms.
  • the reaction between (2) and (3) is usually carried out under acidic conditions, and the acid used is, for example, hydrogen chloride, sulfuric acid, nitric acid, boron trifluoride, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid It is an acid, and the amount of the acid used is 1 to 2 molar equivalents to (2).
  • the aldehyde (3) is used in an amount of 1 to 2 molar equivalents.
  • Non-protonic solvents such as chloromethylene chloride, chloroform, 1,2-dichloroethane, benzene, toluene, xylene, getyl ether, tetrahydrofuran, etc. A solvent is used.
  • the reaction is carried out at a temperature ranging from 0 ° C to the boiling point of the solvent, and the reaction time is 2 to 10 hours.
  • Water generated in the reaction can be removed by azeotropic distillation, but molecular sieves may be used as a dehydrating agent.
  • the reaction solution is neutralized with aqueous sodium bicarbonate and the like, and then treated in a conventional manner (extraction with an organic solvent, purification of the oil obtained by evaporation of the solvent by chromatography or crystallization) and the compound (la).
  • mercaptan (10) or its acetate derivative (11) under basic conditions to produce the desired compound (lb).
  • solvent used in the reaction include alcohols such as methanol, ethanol, and propanol, dimethylformamide, dimethylacetamide, dimethylsulfoxide, acetatenitol, and tetrahydro.
  • a non-protonic solvent such as drofuran is suitable, but when the reaction is carried out in the non-protonic solvent using the acetyl derivative (11), coexistence of alcohols or water is required.
  • the bases used in the reaction are sodium hydride, sodium methoxide, sodium ethoxide, lithium methoxide, potassium tert-butoxide, lithium hydroxide, and hydroxide. They are sodium and potassium hydroxide, and the amount used is 0.1 to 2 molar equivalents relative to compound (9).
  • Mercaptan (10) or its acetate derivative (11) is used in 1 to 3 molar equivalents.
  • the reaction temperature is from room temperature to 100 ° C, and the reaction time is from 2 to 10 hours.
  • the compound (1b) can be obtained by treating the reaction solution according to a conventional method (extraction with an organic solvent, removal of the solvent by distillation, and purification of the resulting oil by column chromatography or recrystallization).
  • R 4 SH (10) or R 4 SAc (11) used in the above reaction is, for example, It can be obtained by the following method. That is, the compound (10a) or (1la) in which A in R 4 is a 1,3-dioxane ring is a known compound (A) described in JP-A-8-333550. It can be prepared according to the method described in the same publication according to the following process chart, using 12) as a starting material. See Reference Examples 5, 6, and 7 in the publication for the reaction conditions and the separation method in each step. ) p — (C ⁇ C) q -Ar 2 H
  • Compound A in R 4 is cyclohexane ring or Te Jewishi Doropiran ring cyclohex (1 0 b), (1 0 c), (lib) and (1 1 c), the JP-8 - 3 3 Three
  • the aldehyde (13b) described in Reference Example 40 of Japanese Patent Publication No. 350/130 or the aldehyde (13c) described in Reference Example 21 of this specification is used as a starting material.
  • each can be produced according to the following process chart. The reaction conditions and isolation method in each step are described in Reference Examples 41, 42, 43 of JP-A-8-333350, and Reference Examples 24, 25, 26 of this specification. See
  • X represents a chlorine atom, a bromine atom or an iodine atom
  • Ar2, ⁇ and q have the same meanings as described above.
  • the alcohol (15) in the above formula may be replaced with a corresponding aldehyde dicarboxylic acid ester (eg, (3a), (3b), (3c), (4), (5) Or (8)) can be reduced by a conventional method with a reducing agent such as diisobutylaluminum hydride. See Reference Example 4 for the reaction conditions and isolation method in each step.
  • a reducing agent such as diisobutylaluminum hydride
  • the solvent to be used is not particularly limited as long as it does not hinder the reaction and dissolves the starting material to some extent, but is preferably a halogenated hydrocarbon such as dichloromethane or chloroform. Can be.
  • the oxidizing agent to be used include peracetic acid and m-methyl perbenzoic acid.
  • the reaction temperature is usually 30 minutes to 2 hours.
  • the present invention will be described in more detail with reference to Examples, Reference Examples, Test Examples, and Production Examples, but the scope of the present invention is not limited thereto.
  • Mass vector m / e 601 (M + ), 523, 448, 378, 318, 262, 224 (100%), 196, 152, UK " ⁇ ' ⁇ ⁇ 'ZSZ' (00 ⁇ ) ⁇ ' ⁇ '69C' ZOl '' ITS '689' ⁇ 9 'C99: s / m M ⁇ ⁇ - ⁇ .
  • the title compound as colorless crystals was obtained in a yield of 100% from 2-naphthaldehyde and triphenylphosphoranilideneacetic acid methyl ester.
  • the solvent was removed under reduced pressure, and the residue was recrystallized from a benzene-hexane mixed solvent to obtain 128 mg of the title compound having a melting point of 100 to 101 ° C as colorless crystals. Further, the mother liquor was subjected to column chromatography using 7 g of silica gel, and eluted with a mixed solvent of ethyl acetate-benzene (1: 9) to obtain 106 mg of the title compound (total yield of 8 mg). 4%).
  • Oxalyl chloride (300 mg, 2.4 mmol) was added to a solution of dimethyl sulfoxide (184 mg, 2.4 mm 01) in dichloromethane (5 ml) at 178 ° C. ) was added. In addition, at 178 ° C (5-chloro-1-methyl-2-indolinyl) A solution of ethanol (230 mg, 1.2 mmol) in dichloromethane (1.5 ml) was added. Five minutes later, triethylamine (480 mg, 4.7 mmo 1) was added. Water, black form and ethyl acetate were added, and the mixture was stirred at room temperature. Insolubles were removed by filtration, and the organic layer was separated and washed with brine.
  • Triphenyl chloride [[6— (2,2,3,3—tetrafluoropropoxy) —2—naphthyl] methyl] phosphonium
  • the Ca Njida-Arvika Nsu (Candida albicans) 4 ⁇ 9 x 1 0 6 or mice inoculated with (1 group 1 0 rats), and the 1, 4, 2 4 hours after drug 2 0 mg / kg was orally administered The survival rate up to 21 days after infection was examined.
  • the results of comparison between the compound of the present invention and commercially available fluconazole are shown in Table 2. From these results, it is clear that the compound of the present invention exhibits excellent antifungal activity.
  • the powder of the above formulation is mixed, wet-granulated using corn starch paste, dried, and then tableted with a tableting machine to give one tablet of 200 mg. These tablets can be sugar-coated if necessary.
  • the compound of the present invention and a pharmacologically acceptable salt thereof exhibit excellent antifungal activity, are stable to acids, have excellent absorbability, have low toxicity, and are resistant to mycoses in humans and animals. Useful.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne des composés de triazole représentés par la formule générale (I), lesquels composés conviennent particulièrement comme antimycosiques. Dans cette formule, Ar1 est un groupe phényl éventuellement substitué. Ar2 est un groupe naphtyl éventuellement substitué. R1 est un groupe alkyl inférieur. n, p et q valent chacun 0, 1, ou 2. A est un homocycle ou un hétérocycle aliphatique.
PCT/JP1998/000449 1997-02-04 1998-02-04 Derives triazole WO1998033778A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU57795/98A AU5779598A (en) 1997-02-04 1998-02-04 Triazole derivatives

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP9/21473 1997-02-04
JP2147397 1997-02-04

Publications (1)

Publication Number Publication Date
WO1998033778A1 true WO1998033778A1 (fr) 1998-08-06

Family

ID=12055954

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1998/000449 WO1998033778A1 (fr) 1997-02-04 1998-02-04 Derives triazole

Country Status (2)

Country Link
AU (1) AU5779598A (fr)
WO (1) WO1998033778A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1083175A3 (fr) * 1999-09-09 2001-04-11 Sankyo Company Limited Dérivés de triazole à activité antifongique
JP3240129B1 (ja) 1999-09-09 2001-12-17 三共株式会社 トリアゾール抗真菌剤
CZ297383B6 (cs) * 1999-09-09 2006-11-15 Sankyo Company Limited Deriváty triazolu s protiplísnovými úcinky

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0473387A2 (fr) * 1990-08-26 1992-03-04 Sankyo Company Limited Dérivés du triazole antifongiques, leurs préparation et applications
EP0510700A2 (fr) * 1991-04-26 1992-10-28 Takeda Chemical Industries, Ltd. Dérivés d'azole, leurs préparation et application
EP0552974A1 (fr) * 1992-01-24 1993-07-28 ROUSSEL MORISHITA Co., Ltd. Dérivé de 1-aryl-2-(1H-1,2-4-triazol-1-yl)éthanol et composition fongicide le contenant
WO1995025107A1 (fr) * 1994-03-12 1995-09-21 Yuhan Corporation Composes triazoliques et leurs procedes de preparation
WO1996031491A1 (fr) * 1995-04-06 1996-10-10 Sankyo Company, Limited Agent antifongique de triazole

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0473387A2 (fr) * 1990-08-26 1992-03-04 Sankyo Company Limited Dérivés du triazole antifongiques, leurs préparation et applications
EP0510700A2 (fr) * 1991-04-26 1992-10-28 Takeda Chemical Industries, Ltd. Dérivés d'azole, leurs préparation et application
EP0552974A1 (fr) * 1992-01-24 1993-07-28 ROUSSEL MORISHITA Co., Ltd. Dérivé de 1-aryl-2-(1H-1,2-4-triazol-1-yl)éthanol et composition fongicide le contenant
WO1995025107A1 (fr) * 1994-03-12 1995-09-21 Yuhan Corporation Composes triazoliques et leurs procedes de preparation
WO1996031491A1 (fr) * 1995-04-06 1996-10-10 Sankyo Company, Limited Agent antifongique de triazole

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1083175A3 (fr) * 1999-09-09 2001-04-11 Sankyo Company Limited Dérivés de triazole à activité antifongique
JP3240129B1 (ja) 1999-09-09 2001-12-17 三共株式会社 トリアゾール抗真菌剤
US6337403B1 (en) 1999-09-09 2002-01-08 Sankyo Company, Limited Triazole derivatives having antifungal activity
US6391903B1 (en) 1999-09-09 2002-05-21 Sankyo Company, Limited Triazole derivatives having antifungal activity
US6392082B1 (en) 1999-09-09 2002-05-21 Sankyo Company, Limited Triazole derivatives having antifungal activity
CZ297383B6 (cs) * 1999-09-09 2006-11-15 Sankyo Company Limited Deriváty triazolu s protiplísnovými úcinky

Also Published As

Publication number Publication date
AU5779598A (en) 1998-08-25

Similar Documents

Publication Publication Date Title
JP5218737B2 (ja) スフィンゴシン−１−リン酸結合阻害物質
HU210165B (en) Process for producing heterocyclic compounds and pharmaceutical compositions comprising them
FR2800375A1 (fr) Derives tricycliques d'acide pyrazolecarboxylique, leur preparation, les compositions pharmaceutiques en contenant
EP0434249A2 (fr) Dérivés de benzofurane
JP4709148B2 (ja) フルオロビニル基を有する抗真菌性アゾール誘導体及びその製造方法
EP0433149B1 (fr) Antagonistes de la sérotonine, leur préparation et les médicaments les contenant
FR2618437A1 (fr) Nouveaux derives du benzopyranne, leur preparation et les medicaments qui les contiennent
JPH0699426B2 (ja) １，３―ジオキサンアルケン酸誘導体、その製造法、ならびに虚血性心臓疾患、脳血管性疾病、喘息性疾患および炎症性疾患の治療に使用する製薬学的組成物
FR2542315A1 (fr) Nouveaux composes azoliques, leur preparation et leur utilisation comme antifongiques et fongicides
JPH0468310B2 (fr)
US6306880B1 (en) Triazole antifungal agent
CA2021250A1 (fr) Medicaments a base de derives de 1h-benzoxadiazine-4, 1, 2, nouveaux derives et leurs procedes de preparation
FI101222B (fi) Menetelmä terapeuttisesti aktiivisten kinolin-2-yylimetoksifenyylijohd annaisten valmistamiseksi
HU203722B (en) Process for producing substituted hydroxyamines and pharmaceutical compositions containing them
KR100462072B1 (ko) 불소화 비닐기가 치환된 항진균성 아졸계 유도체 및 그의제조방법
WO1998033778A1 (fr) Derives triazole
FR2510113A1 (fr)
JP3622882B2 (ja) トリアゾール誘導体を含有する医薬
WO1999002524A1 (fr) Composes antifongiques a base de triazole
JPH06503818A (ja) 官能化されたビニルアゾールを含有する製薬学的調整剤、医薬品を製造するための該ビニルアゾールの使用、ビニルアゾールそれ自体およびその製造法
JPH10279567A (ja) トリアゾール誘導体
JP2902345B2 (ja) トリアゾール抗真菌剤
JPH0468309B2 (fr)
HU198466B (en) Process for producing dioxanyl-hexenecarboxylic acid derivatives and pharmaceutical compositions comprising these compounds
JP2000044547A (ja) トリアゾール誘導体を含有する抗真菌剤

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU BR CA CN CZ HU ID IL KR MX NO NZ PL RU TR US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE

121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载