US3660577A - N-trityl-imidazoles as antifungal agents - Google Patents

N-trityl-imidazoles as antifungal agents Download PDF

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Publication number
US3660577A
US3660577A US758594A US3660577DA US3660577A US 3660577 A US3660577 A US 3660577A US 758594 A US758594 A US 758594A US 3660577D A US3660577D A US 3660577DA US 3660577 A US3660577 A US 3660577A
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Prior art keywords
methyl
imidazole
diphenyl
phenyl
chlorophenyl
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US758594A
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Karl-Heinz Buchel
Erich Regel
Manfred Plompel
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Bayer AG
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Bayer AG
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    • 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
    • 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
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C07D235/08—Radicals containing only hydrogen and carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/18—Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2

Definitions

  • R, R and R are hydrogen, lower alkyl or phenyl, or R and R together form an anellated benzene ring,
  • X, X and X are alkyl of 1 to 12 carbon atoms or an electro-negative moiety
  • n, n and n are an integer from 0 to 2, or pharmaceutically acceptable acid salts thereof may be produced by reacting a silver salt or alkali metal salt of an imidazole of the formula:
  • the present invention is concerned with N-trityl-imidazoles and salts thereof and the production of such compounds. More particularly, the present invention is concerned with N-trityl-amidazoles and salts thereof of the formula:
  • R, R and R are hydrogen, lower alkyl or phenyl, or R and R together form an anellated benzene ring
  • X, X' and X" are alkyl of 1 to 12 carbon atoms or an electro-negative moiety
  • n, n and n" are an integer from 0 to 2, or pharmaceutically acceptable acid salts thereof.
  • R, R or R are alkyl moieties, those having 1 to 4 carbon atoms are preferred.
  • X, X or X" is an alkyl moiety, it is preferred that such have 1 to 12 carbon atoms and such moieties having 1 to 4 carbon atoms are especially preferred.
  • Electro-negative substituents which are particularly preferred are the halogens, i.e., fluorine, chlorine, bromine and iodine, N0 CF CN, as well as S-lower alkyl and O-lower alkyl; it is preferred that the alkyl moieties have 1 to 4 carbon atoms.
  • alkyl and lower alkyl comprises straight chain as well as branched chain alkyl moieties and also include those containing a double bond.
  • the salts of the N-trityl-imidazoles (I) are the pharmaceutically acceptable non-toxic acid salts.
  • suitable acids are the hydrohalic acids (hydrochloric being particularly preferred), phosphoric acid, monoand bifunctional carboxylic acids, such as acetic acid, propionic acid, maleic acid, succinic acid, fumaric acid, tartaric acid, citric acid, salicylic acid, sorbic acid, lactic acid and 1,5- naphthalene-disulphonic acid.
  • the hydrohalides, especially the hydrochlorides, lactates and salicylates are of particular 'value.
  • N-trityl-imidazoles have the formula:
  • X "X",.- (II) wherein X, X and X" are alkyl of l to 12 carbon atoms or electro-negative substituents and n, n and n" are 1 or 2.
  • substituent values are those where X is fluorine, chlorine, bromine, iodine, N0 CF CN, SCH OCH, and n" is 1.
  • the compounds of the present invention can be prepared according to techniques per se known, such as by reacting silver salts or alkali metal salts, in particular the potassium salts of imidazoles of the Formula III with trityl halides of the Formula IV:
  • R, R and R X and n have the above meanings and Hal is chlorine, bromine or iodine, in an inert solvent such as benzene, toluene, hexane, cyclohexane, or diethyl ether, at a temperature of from about 20 C. to about 110 C. [cf. Chem. Ber. 92, 92 (1959); 93, 570 (1960)].
  • the compounds of the present invention can also be prepared according to techniques per se known by reacting imidazole derivatives of the Formula III with tritylcarbinols (cf. the reaction of the carbinol corresponding to the halide IV with secondary amines).
  • the imidazole is generally used in an excess of up to about If the process is carried out under pressure, molar amounts may be used.
  • dehydrating agents such as eg alkaline earth metal oxides (MgO, BaO, CaO) and of A1 0, approximately molar amounts being generally used, but possibly also an excess of up to about 2-3 moles.
  • CeHs 1 mole p-chlorophenyl-diphenyl-methyl carbinol is mixed with about 2 moles imidazole and the mixture is heated, without a Solvent, at about 180 C. for hours. After cooling, the reaction product is reprecipitated from Xylene in order to remove the excess imidazole. After another reprecipitation from benzene light petrol, the pure 1-[p-chlorophenyl-diphenyl-methyl]-imid*azole is obtained. M.P. l40-143 C.; yield 53% of theory.
  • the same compound can also be obtained, when finely powdered silver salt of imidazole is suspended with the equimolar amount of p-chlorophenyl-diphenyl-methyl chloride in absolute benzene, the mixture is heated with stirring and with the exclusion of light at boilingtemperature for about 3 hours, the precipitated silver chloride is subsequently filtered off and the residue remaining after removal of the solvent is recrystallised from benzene/light petrol.
  • the other compounds (I, II) can also be obtained according to the above processes.
  • the conversion of the free compounds into the salts is likewise carried out in known manner.
  • N-trityl-imidazoles N-triphenyl-methyl-imidazolium lactate 31 g. N-trityl-imidazole are dissolved by heating in acetonitrile and 10 g. (0.11 mole) d,l-lactic acid are subsequently added. The residue remaining after distilling off the solvent is caused to crystallise by covering it with ether, the crystallisation product is washed with ether and dried.
  • N-triphenylmethyl-imidazolium maleate 106-117 N-triphenylmethyl-imidazolium tartrate -180 N-triphenylmethyl-imidazolium citrate 138-145 N-triphenylmethyl-imidazolium acetate 231 N-triphenylmethyl-imidazolium salicylate 145-168 N-triphenylmethyl-imidazolium sorbate 148-160 N-triphenylmethyl-imidazolium succinate 188-189 N-triphenylmethyl-imidazolium fumarate 200-206 1 (p-chlorophenyl-diphenyl-methyl)-imidazoli- 1 (p-cyanophenyl-diphenyl-methyl)-imid l umlactatei-i-qufin-i-iin
  • the previously known antimycotics are effective either only against yeasts, such as e.g. Amphotericin B, or only against
  • the compounds (I, II) and their salts are effective against hyphomycetes as well as against yeasts, even in the case of oral administration. It is another advantage that the compounds according to the invention are well tolerated by warm-blooded animals.
  • the compounds can be used as antimycotics, inter alia, in the form of an aqueous emulsion, suspension or solution which can be administered per os. It is also possible to use aqueous solutions of the new salts of the said compounds (I).
  • Such compounds and their salts with hydrochloric acid, lactic acid or salicyclic acid are particularly useful.
  • the following usages and dosage ranges are used for the compounds of the present invention: (a) for use with humans (1) dermatomycoses, caused by fungi of the species Trichophytes, Microsporium, Epidermophytes, Aspergillus, Candida albicans and other yeasts; (2) organomycoses caused by yeasts, mould fungi and dermatophytes; (b) for veterinary use dematomycoses and organomycoses caused by yeasts,
  • the compounds of the present invention are administered orally or parenterally as Well as locally in the form of solutions, e.g., alcohol, preferably ethanol and isopropanol, buffer solutions, powders, tablets.
  • solutions e.g., alcohol, preferably ethanol and isopropanol, buffer solutions, powders, tablets.
  • the dosage range for humans is in the range of from about 20 to about 100 mg./kg. and preferably from about 40 to about 60 mg./ kg. Administration is generally recommended at intervals of about 12 hours and such administration should be continued for from about 10 to about 60 days.
  • the compounds of the present invention can be used either as such or in combination with pharmaceutically acceptable carriers.
  • suitable forms for administration in combination with various inert carriers are tablets, capsules, powders, sprays, aqueous suspensions, injectable solutions, elixirs, syrups and the like.
  • Carriers of this type comprise solid extenders or fillers, a sterile aqueous medium as well as Ivarious non-toxic organic solvents and the like.
  • the tablets and the like suitable for oral administration can be provided with an addition of saccharin or a similar additive.
  • the therapeutically active compound should be present in the total mixture at a concentration of about 0.5 to percent by weight, i.e., in quantities which suffice to attain the range of dosage mentioned above.
  • tablets may also contain additives such as sodium citrate, calcium carbonate and dicalcium phosphate together with various additives such as starch, preferably potato starch and the like, and binders such as polyvinyl pyrrolidone, gelatin and the like. It is further possible to add lubricants such as magnesium stearate, sodium lauryl-sulphate and talc for producing tablets.
  • the active ingredient may be used together with various agents for improving the flalvor, dyestuffs, emulsifiers and/ or diluents, such as water, ethanol, propylene-glycol, glycerol and other compounds or combinations of this type.
  • aqueous solutions of the active ingredients in sesame or peanut oil or in aqueous propylene-glycol of N,N-dimethyl formamide, as well as sterile aqueous solutions if the compounds are water-soluble.
  • aqueous solution should be buffered in the usual manner, if required, and the liquid diluent should previously be rendered isotonic by the addition of the necessary amount of salt or glucose.
  • aqueous solutions are particularly suitable for intravenous, intramuscular and intraperitoneal injections.
  • a dostage of 40 mg./kg. administered at intervals of 12 hours result in a blood level of between 5 and 11 /ml.
  • the half-life period in human serum in vivo amounts to 6 hours on the average.
  • Up to 30 to 40% of the administered amount of the substance are excreted with the urine in active form.
  • the resorption quota amounts to more than 70% in the case of oral administration.
  • mice, rats, rabbits, dogs and cats lies between about 600 and 2200 mg. of the stated compounds/ kg. body weight in the case of oral administration.
  • the present invention also includes pharmaceutical compositions comprising at least one of the N-trityl-imidazoles or salts thereof in admixture with a solid or liquid diluent or carrier which may be any of the conventional diluents or carriers used in pharmaceutical compositions.
  • the present invention also includes unit dosage forms of medication which comprise at least one of the compounds of the present invention either alone or in admixture with a solid or liquid diluent or carrier.
  • the compounds of the present application may include a protective envelope or cover containing the active compound within.
  • Unit dosage form means that the composition is in the form of discrete portions, each containing a unit dose or a multiple or sub-multiple of the unit dose of the active ingredient which is the compound of the present invention.
  • Such portions may, for example, be in monolithic coherent form, such as tablets, suppositories, pills or drages; in wrapped or concealed form, such as wrapped powders, cachets, sachets or capsules, in ampules such as in sterile solution; or in other forms known to the art.
  • An antifungal composition for administration to humans and animals which comprises an amount of a compound of the formula:
  • X is fluorine, chlorine, bromine or iodine
  • n" is 1, or a pharmaceutically acceptable, non-toxic acid salt thereof, sufficient to be therapeutically effective against fungi pathogenic to humans and animals, in combination with a pharmaceutically acceptable non-toxic inert diluent or carrier.
  • An antifungal composition according in the form of a sterile solution.
  • An antifungal composition according in unit dosage form.
  • salt is selected from the group consisting of hydrochloride, phosphate, acetate, propionate, maleate, succinate, fumarate, tartarate, citrate, salicylate, sorbate, lactate and 1,S-naphthalene-disulphonate.
  • An antifungal composition according to claim 1 wherein the compound is l-(p-chlorophenyl-diphenylmethyl)-imidazole.
  • An antifungal composition according to claim 1 wherein the compound is 1-(o-chlorophenyl-diphenylto claim to claim to claim to claim to claim HHHHH to claim methyl-imidazole or a pharmaceutically acceptable nontoxic salt thereof.
  • An antifungal composition according to claim 1 wherein the compound is 1-(m-fluorophenyl-diphenylmethyl)-imidazole.
  • An antifungal composition according to claim 1 wherein the compound is selected from the group consisting of 1- (p-chlorophenyl-diphenyl methyl -imidazolium chloride,
  • An antifungal composition for administration to humans and animals which comprises an amount of 1-(0- chlorophenyl-diphenyl-methyl)-imidazole suflicient to be therapeutically effective against fungi pathogenic to humans and animals, in combination with a pharmaceu' tically acceptable non-toxic inert diluent or carrier.
  • An antifungal composition for administration to humans and animals which comprises an amount of l-(ochlorophenyl-diphenyl-methyl)-imidazolium chloride sufficient to be therapeutically effective against fungi pathogenic to humans and animals, in combination with a pharmaceutically acceptable non-toxic inert diluent or carrier.
  • XIII wherein X" is fluorine, chlorine, bromine or iodine, and n" is 1, or a pharmaceutically acceptable non-toxic salt thereof.
  • a method according to claim 19 wherein the therapeutically effective amount is from about 20 to about mg./ kg. for from about 10 to about 60 days.
  • a method according to claim 19 wherein the therapeutically elfective amount is from about 40 to about 60 mg./ kg. administered for from about to about 60 days.
  • a method according to claim 19, wherein the salt is selected from the group consisting of phosphate, acetate, propionate, maleate, succinate, fumarate, tartarate, citrate, salicylate, sorbate, lactate and 1,S-naphthalene-disulphonate.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
US758594A 1967-09-15 1968-09-09 N-trityl-imidazoles as antifungal agents Expired - Lifetime US3660577A (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DEF0053504 1967-09-15
LU57488 1968-12-06
US21852472A 1972-01-17 1972-01-17

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US758594A Expired - Lifetime US3660577A (en) 1967-09-15 1968-09-09 N-trityl-imidazoles as antifungal agents
US13797A Expired - Lifetime US3705172A (en) 1967-09-15 1970-02-24 N-trityl-imidazoles
US36395A Expired - Lifetime US3657445A (en) 1967-09-15 1970-05-11 N-trityl-imidazoles for treating fungal infections
US36425A Expired - Lifetime US3655899A (en) 1967-09-15 1970-05-11 N-trityl-imidazoles for treating fungal infections
US36396A Expired - Lifetime US3660576A (en) 1967-09-15 1970-05-11 N-trityl-imidazoles for treating fungal infections
US36426A Expired - Lifetime US3655900A (en) 1967-09-15 1970-05-11 N-trityl-imidazoles for treating fungal infections
US36424A Expired - Lifetime US3658956A (en) 1967-09-15 1970-05-11 N-trityl-imidazoles for treating fungal infections
US36394A Expired - Lifetime US3657442A (en) 1967-09-15 1970-05-11 N-trityl-imidazoles for treating fungal infections
US00126277A Expired - Lifetime US3720770A (en) 1967-09-15 1971-03-19 1-(p-chloro-m-nitrophenyl-diphenylmethyl)-imidazole as an antifungal agent
US00161274A Expired - Lifetime US3839573A (en) 1967-09-15 1971-07-09 Antifungal compositions and methods of treatment employing n-trityl imidazoles
US00218523A Expired - Lifetime US3711499A (en) 1967-09-15 1972-01-17 N-trityl-imidazoles
US00218526A Expired - Lifetime US3711501A (en) 1967-09-15 1972-01-17 N-trityl-imidazoles
US00218524A Expired - Lifetime US3717657A (en) 1967-09-15 1972-01-17 N-trityl-imidazoles
US00218525A Expired - Lifetime US3711500A (en) 1967-09-15 1972-01-17 N-trityl-imidazoles
US00218521A Expired - Lifetime US3711498A (en) 1967-09-15 1972-01-17 N-trityl-imidazoles
US00218519A Expired - Lifetime US3767668A (en) 1967-09-15 1972-01-17 Process for the production of n-trityl-imidazoles

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US13797A Expired - Lifetime US3705172A (en) 1967-09-15 1970-02-24 N-trityl-imidazoles
US36395A Expired - Lifetime US3657445A (en) 1967-09-15 1970-05-11 N-trityl-imidazoles for treating fungal infections
US36425A Expired - Lifetime US3655899A (en) 1967-09-15 1970-05-11 N-trityl-imidazoles for treating fungal infections
US36396A Expired - Lifetime US3660576A (en) 1967-09-15 1970-05-11 N-trityl-imidazoles for treating fungal infections
US36426A Expired - Lifetime US3655900A (en) 1967-09-15 1970-05-11 N-trityl-imidazoles for treating fungal infections
US36424A Expired - Lifetime US3658956A (en) 1967-09-15 1970-05-11 N-trityl-imidazoles for treating fungal infections
US36394A Expired - Lifetime US3657442A (en) 1967-09-15 1970-05-11 N-trityl-imidazoles for treating fungal infections
US00126277A Expired - Lifetime US3720770A (en) 1967-09-15 1971-03-19 1-(p-chloro-m-nitrophenyl-diphenylmethyl)-imidazole as an antifungal agent
US00161274A Expired - Lifetime US3839573A (en) 1967-09-15 1971-07-09 Antifungal compositions and methods of treatment employing n-trityl imidazoles
US00218523A Expired - Lifetime US3711499A (en) 1967-09-15 1972-01-17 N-trityl-imidazoles
US00218526A Expired - Lifetime US3711501A (en) 1967-09-15 1972-01-17 N-trityl-imidazoles
US00218524A Expired - Lifetime US3717657A (en) 1967-09-15 1972-01-17 N-trityl-imidazoles
US00218525A Expired - Lifetime US3711500A (en) 1967-09-15 1972-01-17 N-trityl-imidazoles
US00218521A Expired - Lifetime US3711498A (en) 1967-09-15 1972-01-17 N-trityl-imidazoles
US00218519A Expired - Lifetime US3767668A (en) 1967-09-15 1972-01-17 Process for the production of n-trityl-imidazoles

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US (16) US3660577A (enrdf_load_stackoverflow)
BE (1) BE720801A (enrdf_load_stackoverflow)
FR (2) FR1597530A (enrdf_load_stackoverflow)
GB (1) GB1170188A (enrdf_load_stackoverflow)
LU (1) LU57488A1 (enrdf_load_stackoverflow)

Cited By (13)

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US3980780A (en) * 1970-03-23 1976-09-14 Bayer Aktiengesellschaft N-Methyl-imidazole derivatives for treating mycotic infections
US4267169A (en) * 1978-07-22 1981-05-12 Toko Yakuhin Kogyo Kabushiki Kaisha Novel preparation of clotrimazole
EP0165777A1 (en) * 1984-06-18 1985-12-27 Eli Lilly And Company Aromatase inhibiting N-substituted imidazole and triazole derivative
US4775678A (en) * 1984-10-01 1988-10-04 Schering Corporation Clotrimazole cream
US5100908A (en) * 1990-03-06 1992-03-31 Ss Pharmaceutical Co., Ltd. Antimycotic external imidazole preparations
US5149707A (en) * 1988-07-28 1992-09-22 J. Uriach & Cia, S.A. 1-((2-fluorophenyl)(4-fluorophenyl)phenylmethyl)-1h-imidazole useful as antifungal agent
US5177099A (en) * 1989-04-10 1993-01-05 Sociedad Espanola De Especialidades Farmaco-Terapeuticas S.A. Dichloro-substituted imidazole derivatives as antifungal agents
US5711954A (en) * 1992-06-08 1998-01-27 Schering-Plough Healthcare Products, Inc. Stable imidazole anti-fungal powder compositions
US6103733A (en) * 1998-09-09 2000-08-15 Bachmann; Kenneth A. Method for increasing HDL cholesterol levels using heteroaromatic phenylmethanes
US6545028B2 (en) * 1997-11-14 2003-04-08 Neurosearch A/S Chemical compounds having ion channel blocking activity for the treatment of immune dysfunction
US20060211632A1 (en) * 2005-03-17 2006-09-21 Bachmann Kenneth A PXR agonists for cardiovascular disease
US20170112824A1 (en) * 2015-10-23 2017-04-27 Wright State University Combination therapies for the treatment of fungal infections
WO2018115319A2 (en) 2016-12-23 2018-06-28 Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) Inhibitors of cytochrome p450 family 7 subfamily b member 1 (cyp7b1) for use in treating diseases

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IL33324A (en) * 1968-11-29 1972-09-28 Bayer Ag N-substituted imidazoles and their salts,their production,and pharmaceutical preparations containing them
DE2009020C3 (de) * 1970-02-26 1979-09-13 Bayer Ag, 5090 Leverkusen Verfahren zur Herstellung von N-(l,l,l-trisubstituierten)-Methylazolen
US3764609A (en) * 1970-06-22 1973-10-09 Koninklijke Pharma Fab Nv 1 (dibenzo {8 4,d{9 {0 cyclohepten-5-yl), 1-(dibenzo {8 a,d{9 {0 cycloheptan-5-yl) and 1-(dibenzo {8 a,d{9 {0 cyclooctanyl)imidazoles
DE2037610A1 (de) * 1970-07-29 1972-02-03 Bayer Ag Neue alpha-substituierte Benzyl-azole, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
US4117142A (en) * 1972-03-22 1978-09-26 Bayer Aktiengesellschaft Disubstituted triphenylmethylmidazoles for treating mycotic infections
DE2213863C3 (de) * 1972-03-22 1982-05-13 Bayer Ag, 5090 Leverkusen Disubstituierte Triphenylmethylimidazole, Verfahren zu ihrer Herstellung sowie diese enthaltende Arzneimittel
DE2314985A1 (de) * 1973-03-26 1974-10-17 Hoechst Ag 1-(imidazol-1-yl)-isochinoline und verfahren zu ihrer herstellung
JPS6048486B2 (ja) * 1976-01-01 1985-10-28 木場 常義 抗リウマチ剤
FR2387658A1 (fr) * 1977-03-25 1978-11-17 Ciba Geigy Ag Procede pour combattre les microorganismes
US4216333A (en) * 1978-10-30 1980-08-05 Sumitomo Chemical Company, Limited Process for preparing N-tritylimidazole compounds
US4439441A (en) * 1979-01-11 1984-03-27 Syntex (U.S.A.) Inc. Contraceptive compositions and methods employing 1-substituted imidazole derivatives
JPS5692887A (en) * 1979-12-05 1981-07-27 Sumitomo Chem Co Ltd N-substituted imidazole derivative
JPS58150566A (ja) * 1982-03-03 1983-09-07 Yoshitomi Pharmaceut Ind Ltd 新規イミダゾ−ル誘導体
US4937250A (en) * 1988-03-07 1990-06-26 Ciba-Geigy Corporation Alpha-heterocycle substituted tolunitriles
US4749713A (en) * 1986-03-07 1988-06-07 Ciba-Geigy Corporation Alpha-heterocycle substituted tolunitriles
US4978672A (en) * 1986-03-07 1990-12-18 Ciba-Geigy Corporation Alpha-heterocyclc substituted tolunitriles
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US3980780A (en) * 1970-03-23 1976-09-14 Bayer Aktiengesellschaft N-Methyl-imidazole derivatives for treating mycotic infections
US4267169A (en) * 1978-07-22 1981-05-12 Toko Yakuhin Kogyo Kabushiki Kaisha Novel preparation of clotrimazole
EP0165777A1 (en) * 1984-06-18 1985-12-27 Eli Lilly And Company Aromatase inhibiting N-substituted imidazole and triazole derivative
US4755526A (en) * 1984-06-18 1988-07-05 Eli Lilly And Company Method of inhibiting aromatase
US4775678A (en) * 1984-10-01 1988-10-04 Schering Corporation Clotrimazole cream
US5149707A (en) * 1988-07-28 1992-09-22 J. Uriach & Cia, S.A. 1-((2-fluorophenyl)(4-fluorophenyl)phenylmethyl)-1h-imidazole useful as antifungal agent
US5177099A (en) * 1989-04-10 1993-01-05 Sociedad Espanola De Especialidades Farmaco-Terapeuticas S.A. Dichloro-substituted imidazole derivatives as antifungal agents
US5100908A (en) * 1990-03-06 1992-03-31 Ss Pharmaceutical Co., Ltd. Antimycotic external imidazole preparations
US5711954A (en) * 1992-06-08 1998-01-27 Schering-Plough Healthcare Products, Inc. Stable imidazole anti-fungal powder compositions
US6545028B2 (en) * 1997-11-14 2003-04-08 Neurosearch A/S Chemical compounds having ion channel blocking activity for the treatment of immune dysfunction
US6103733A (en) * 1998-09-09 2000-08-15 Bachmann; Kenneth A. Method for increasing HDL cholesterol levels using heteroaromatic phenylmethanes
US20060211632A1 (en) * 2005-03-17 2006-09-21 Bachmann Kenneth A PXR agonists for cardiovascular disease
US20170112824A1 (en) * 2015-10-23 2017-04-27 Wright State University Combination therapies for the treatment of fungal infections
WO2018115319A2 (en) 2016-12-23 2018-06-28 Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) Inhibitors of cytochrome p450 family 7 subfamily b member 1 (cyp7b1) for use in treating diseases

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Publication number Publication date
US3711499A (en) 1973-01-16
US3657442A (en) 1972-04-18
US3711500A (en) 1973-01-16
FR8112M (enrdf_load_stackoverflow) 1970-07-27
US3655899A (en) 1972-04-11
DE1617481A1 (de) 1971-04-08
US3720770A (en) 1973-03-13
US3660576A (en) 1972-05-02
US3711501A (en) 1973-01-16
DE1617481B2 (de) 1975-07-24
GB1170188A (en) 1969-11-12
US3658956A (en) 1972-04-25
US3657445A (en) 1972-04-18
US3655900A (en) 1972-04-11
US3839573A (en) 1974-10-01
LU57488A1 (enrdf_load_stackoverflow) 1969-03-13
US3767668A (en) 1973-10-23
US3711498A (en) 1973-01-16
US3717657A (en) 1973-02-20
FR1597530A (enrdf_load_stackoverflow) 1970-06-29
US3705172A (en) 1972-12-05
BE720801A (enrdf_load_stackoverflow) 1969-03-13

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