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Publication numberUS3660577 A
Publication typeGrant
Publication dateMay 2, 1972
Filing dateSep 9, 1968
Priority dateSep 15, 1967
Also published asDE1617481A1, DE1617481B2, US3655899, US3655900, US3657442, US3657445, US3658956, US3660576, US3705172, US3711498, US3711499, US3711500, US3711501, US3717657, US3720770, US3767668, US3839573
Publication numberUS 3660577 A, US 3660577A, US-A-3660577, US3660577 A, US3660577A
InventorsKarl-Heinz Buchel, Manfred Plompel, Erich Regel
Original AssigneeBayer Ag
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
N-trityl-imidazoles as antifungal agents
US 3660577 A
Abstract  available in
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Claims  available in
Description  (OCR text may contain errors)

United States Patent Int. Cl. A6 1k 27/00 U.S. Cl. 424273 36 Claims ABSTRACT OF THE DISCLOSURE N-trityl-imidazoles and salts thereof of the formula:

wherein 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, and

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:

R1 N N H with a trityl halide of the formula:

Xn Hal X wherein the substituents are as above defined and Hal is halogen. These compounds are useful as antimycotics.

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:

Ti @t 3,660,577 Patented May 2, 1972 wherein 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, and

n, n and n" are an integer from 0 to 2, or pharmaceutically acceptable acid salts thereof. When R, R or R are alkyl moieties, those having 1 to 4 carbon atoms are preferred. When 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. The term 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. Examples of 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.

In a particularly preferred embodiment of the present invention, the N-trityl-imidazoles have the formula:

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. With regard to Formula Ila, particularly preferred 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:

wherein 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). In this case, 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. Furthermore, it may be expedient to carry out the elimination of water azeotropically in the presence of a high boiling inert organic solvent, such as xylene, chlorobenzenes and the like, at the boiling point of the solvent used. In the absence of solvents, the process is carried out at a temperature range of from about 140 C. to about 230 C. and preferably from about 170 C. to about 190 C.

It may further be expedient to facilitate the elimination of water by working in the presence of 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.

The following table gives the constants of some N- trityl-imidazoles (I, II) by way of example:

M.P.: C. (a) 1-(trisphenyl-methyl)-imidazo1e 226-227 (b) 1-(trisphenyl-methy1)-2-methy1-imidazole 225 (c) 1 (trisphenyl-methyl)-2,4-dimethyl-imidazole 232 (d) 1- (trisphenyl-methyl -4,5-diphenyl-imidazole 228-230 (e) 1- p-chlorophenyl-diphenyl-methyl) -imidaz- Ole 140 (f) 1- (p-fluorophenyl-diphenyl-methyl -imidazole 145 (g) 1-(p-tolyl-diphenyl-methyl)-imidazole 128 (h) l-(trisphenyl-methyl)-benzimidazole 180-181 (i) 1-(o-chlorophenyl-diphenyl-methyl)-imidazole 147-149 (j) 1 (m-chlorophenyl-diphenyl-methyl)-imidazole 114 (k) 1-(p-bromophenyl-diphenyl-methyl -imidazole 152 (l) 1 (o-fiuorophenyl-diphenyl-methyl)-imidazole 185 (m) 1 (m fluorophenyl-diphenyl-methyl)-imidazole 174 (n) 1 (p-nitrophenyl-diphenyl-methyl)-imidazole 160-170 1 (m-trifiuoromethylphenyl-diphenyl-methyl)-imidazole 156 (p) 1(p-cyanophenyl-diphenyl-methyl)-imidazole 164 (q) 1- o-methoxyphenyl-diphenyl-methyl -imidazole 130 (r) 1- p-methylthiophenyl-diphenyl-methyl) -imida-Zole 142 (s) 1- (p-fiuorophenyl-diphenyl-methyl) -2-methyl)-2-methyl-imidazole 199 (t) 1 (p fluorophenyl-p-chlorophenyl-phenylmethyl)-imidazole 144 (u) 1 (p-chlorophenyl-m-fluorophenyl-phenylmethyl)-imidazole 1 16 (v) 1 (p ch10ro-m-nitrophenyl-diphenyl-methyl) -imidazole 150 (w) 1 (p-bromophenyl-p-chlorophenyl-phenylmethyD-imidazole 140 (x) 1-(m-cyanophenyl-diphenyl-methyl)-irnidazole 1 19 (y) 1- (o-cyanophenyl-diphenyl-methyl -imidazole 149-151 EXAMPLE OF PREPARATION 1-[p-chlorophenyl-diphenyl-methyl]-imidazole (e) T1 1.1 cuH,- :J-o1

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.

Byanalogous procedure, l-(tris-phenyl-methyl)-imidazole is produced from 1-tris-phenyl-methyl-carbinol and imidazole and 1-(p-tolyl-diphenyl)-imidazole is produced from 1-p-tolyl-diphenyl-methyl-carbinol and imidazole.

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.

Salts of 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.

Yield 40 g. of a colourless crystalline powder of M.P. -180 C.

N-triphenyl-methyl-imidazolium chloride 31 g. N-trityl-imidazole are dissolved in 400 ml. carbon tetrachloride, and hydrogen chloride is subsequently passed into the solution at room temperature. The hydrochloride is precipitated after some time and filtered off with suction. Colourless crystals of M.P. 155 C.. after recrystallisation from acetone/ether 1:1. Yield 33 g.

The following salts are obtained in an analogous manner:

' M.P.: C. 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 hyphomycetes, such as e.g. Griseofulvin.

In contrast thereto and surprisingly, 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).

THERAPEUTIC' EFFECT (1) In vitro-eifect against human-pathogenic fungi:

MINIMUM INHIBITING CONCENTRATION AS'Y lML Without serum Trich. asteroides Trich. crateriforme Trish. equinum (NL) Trish. equinum, woolly (Hoechst) equinu'm gran. (Hoechst tonsurans vermcosum granulosum- T'rz'ch. interdt'gitale T'rich. megnimi (11) Trichnmentagorphyte (12) Trich. rubmm (13) Microsp. audom'niL- (14) Micro-9p. cam's (NL) (15) M icrosp. cam's (our isolation) (16) Microsp. duboisii" (17; M icrosp. fulvum. (18 Microsp. gallimzen (19) Microsp. felineum. (20) Aapergillus m'ger (24) Can 1 fungistase.

Effect in vivo (a) Experimental candidosis in white mice In the case of oral administration, curative effects can be achieved with daily doses of 2-3 times 0.5-1 mg./mouse/day.

(b) Experimental trychophytia in mice caused by Trich. quinckeanum:

Development of the infection is prevented by daily doses of 1-2 times 1-2 mg./mouse orally.

(c) Experimental trichophytia in guinea pigs caused by trich. ment.

When 15-30 mg. are administered twice per os to guinea pigs weighing 400 grams, a reproducible effect on the course of the infection and rapid healing of the mycotic lesions is found.

Equally effective results are produced when other compounds within the scope of (I) or salts of compounds within the scope of (I) and specifically salts of compounds (a), (e), (f), (g), (i) and (p) are used. Compounds which are unsubstituted in the imidazole ring may be substituted in one phenyl group by a halogen atom, preferably chlorine or fluorine in the o-, mor p-position;

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,

mould fungi and dematophytes.

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.

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.

Nevertheless it may sometimes be necessary to digress from the aforesaid amounts, dependent on the method of administration or also an account of individual reactions to the medicine or on the type of its formulation and the moment in time or the intervals at which it is administered. In some cases, it may be suflicient to use less than the minimum amount stated above, whereas in other cases it may be necessary to go beyond the stated upper limit. If larger amounts are applied, it may be advisable to distribute these over a day in several individual doses.

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. Obviously, the tablets and the like suitable for oral administration can be provided with an addition of saccharin or a similar additive. In the aforesaid case, 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.

In the case of oral administration, obviously, 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. In the case of aqueous suspensions and/ or elixirs which are intended for oral administration, 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.

In the case of parenteral administration, there may be used 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. Such 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. These aqueous solutions are particularly suitable for intravenous, intramuscular and intraperitoneal injections.

In humans, 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.

The LD for 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.

What is claimed is:

1. An antifungal composition for administration to humans and animals which comprises an amount of a compound of the formula:

wherein X" is fluorine, chlorine, bromine or iodine, and

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.

2. An anti-fungal composition according wherein X" is fluorine, chlorine or bromine.

3. An antifungal composition according wherein X is chlorine.

4. An antifungal composition according in the form of a sterile solution.

5. An antifungal composition according in unit dosage form.

6. An antifungal composition according in topical application form.

7. An antifungal composition according to claim 1 in oral administration form.

8. An antifungal composition according to claim 1 wherein 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.

9. An antifungal composition according to claim 1 wherein the compound is l-(p-chlorophenyl-diphenylmethyl)-imidazole.

10. An antifungal composition according to claim 1 wherein the compound is 1-(p-fluorophenyl-diphenylmethyl) -imidazole.

11. An antifungal composition according to claim 1 wherein the compound is 1-(o-chlorophenyl-diphenylto claim to claim to claim to claim HHHHH to claim methyl-imidazole or a pharmaceutically acceptable nontoxic salt thereof.

12. An antifungal composition according to claim 1 wherein the compound is 1-(m-chlorophenyl-diphenylmethyl) -imidazole.

13. An antifungal composition according to claim 1 wherein the compound is 1-(p-bromophenyl-diphenylmethyl -imidazole.

14. An antifungal composition according to claim 1 wherein the compound is 1-(o-fluorophenyl-diphenylmethyl) -imidazole.

15. An antifungal composition according to claim 1 wherein the compound is 1-(m-fluorophenyl-diphenylmethyl)-imidazole.

16. An antifungal composition according to claim 1 wherein the compound is selected from the group consisting of 1- (p-chlorophenyl-diphenyl methyl -imidazolium chloride,

1- p-chlorophenyl-diphenyl-methyl -imidazo1ium lactate,

1- (p-chlorophenyl-diphenyl-methyl -imid azolium salicylate,

1-(m-chlorophenyl-diphenyl-methy1) -imidazolium chloride,

1- (o-chlorophenyl-diphenyl-methyl) -imidazolium chloride,

l- (p-fluoropheny1-diphenyl-methyl -imidazolium chloride,

lp-fiuorophenyl-diphenyl-methyl) -imidazolium lactate,

1- (o-fluorophenyl-diphenyl-methyl -imidazolium lactate,

1- (m-fluorophenyl-diphenyl-methyl -imid azolium lactate and 1- (p-fluorophenyl-diphenyl-methyl -imidazolium salicylate.

17. 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.

18. 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.

19. A method of treating fungal infections in humans and animals which comprises administering to a human or animal so afflicted an amount sufiicient to be therapeutically effective against said infection of a compound of the formula:

XIII! wherein X" is fluorine, chlorine, bromine or iodine, and n" is 1, or a pharmaceutically acceptable non-toxic salt thereof.

20. 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.

21. 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.

22. A method according to claim 19 wherein the administration is parenteral.

23. A method according to claim 19 wherein the administration is by topical application.

24. A method according to claim 19, wherein the administration is oral.

25. A method according to claim 19, wherein the compound is administered in the form of an acid salt.

26. 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.

27. A method according to claim 19, wherein the compound is 1-(p-chlorophenyl-diphenyl-methyl)-imidazole.

28. A method according to claim 19, wherein the compound is 1-(p-fluorophenyl-diphenyl-methyl)-irnidazole.

29. A method according to claim 19, wherein the compound is 1-(o-chlorophenyl-diphenyl-methyl)-imidazole.

30. A method according to claim 19, wherein the compound is 1-(m-chlorophenyl-diphenyl-methyl)-imidazole.

31. A method according to claim 19, wherein the compound is 1-(p-bromophenyl-diphenyl-methyl)-imidazole.

32. A method according to claim 19, wherein the compound is 1-(o-fluorophenyl-diphenyl-methyl)-imidazole.

33. A method according to claim 19, wherein the compound is 1-(m-fluorophenyl-diphenyl-methy1)-imidazole.

34. A method according to claim 19, wherein the compound is selected from the group consisting of 1- (p-chlorophenyl-diphenyl-methyl -imidazolium chloride, v 1- p-chlorophenyl-diphenyl-methyl -imidazolium lactate,

10 1- (p-chlorophenyl-diphenyl-methyl) -imidazolium salicylate,

' l-(m-chlorophenyl-diphenyl-methyl)-imidazolium chloride, 1- (o-chlorophenyl-diphenyl-methyl) -imidazolium chloride, 1-(p-fluorophenyl-diphenyl-methyl)-imidazolium chloride,

, 1-(p-fluorophenyl-diphenyl-methyl)-imidazolium lactate, '1- o-fiuorophenyl-diphenyl-methyl -imidazo1ium I lactate, 1- (m-fiuorophenyl-diphenyl-methyl -imidazolium lactate and 1- (p-fiuorophenyl-diphenyl-methyl -imidazolium salicylate.

References Cited UNITED STATES PATENTS 3,321,366 5/1967 Mussell et al 424-273 JEROME D. GOLDBERG, Primary Examiner U.S. Cl. X.R.

Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US3980780 *Feb 28, 1975Sep 14, 1976Bayer AktiengesellschaftN-Methyl-imidazole derivatives for treating mycotic infections
US4267169 *Jul 12, 1979May 12, 1981Toko Yakuhin Kogyo Kabushiki KaishaCombinations with crotamiton, for use as a fungicide in treating trichophytosis
US4755526 *Jun 18, 1984Jul 5, 1988Eli Lilly And CompanyMethod of inhibiting aromatase
US4775678 *May 8, 1986Oct 4, 1988Schering CorporationClotrimazole cream
US5100908 *Feb 5, 1991Mar 31, 1992Ss Pharmaceutical Co., Ltd.Antimycotic external imidazole preparations
US5149707 *Dec 14, 1990Sep 22, 1992J. Uriach & Cia, S.A.1-((2-fluorophenyl)(4-fluorophenyl)phenylmethyl)-1h-imidazole useful as antifungal agent
US5177099 *May 19, 1992Jan 5, 1993Sociedad Espanola De Especialidades Farmaco-Terapeuticas S.A.Dichloro-substituted imidazole derivatives as antifungal agents
US5711954 *Jun 7, 1993Jan 27, 1998Schering-Plough Healthcare Products, Inc.Stable imidazole anti-fungal powder compositions
US6103733 *Sep 9, 1998Aug 15, 2000Bachmann; Kenneth A.Prevention of atherosclerosis and coronary heart disease; selective induction of hepatic cylochrome p450iiia (cyp3a) activity triphenylmethyl imidazoles or ppyridine substituted by a chlorine or fluorine
US6545028 *Apr 14, 2000Apr 8, 2003Neurosearch A/SAntiepileptic agents, hypotensive agents; monitoring membrane potentials
EP0165777A1 *Jun 14, 1985Dec 27, 1985Eli Lilly And CompanyAromatase inhibiting N-substituted imidazole and triazole derivative
Classifications
U.S. Classification514/396, 548/344.1
International ClassificationC07D235/08, C07D233/62, C07D235/06, C07D235/18, C07D521/00
Cooperative ClassificationC07D235/08, C07D235/18, C07D233/56, C07D249/08, C07D231/12, C07D235/06
European ClassificationC07D235/08, C07D235/06, C07D235/18, C07D233/56, C07D231/12, C07D249/08