US3759946A

US3759946A - 1-aryloxy-4,5-diphenylimidazoles

Info

Publication number: US3759946A
Application number: US00182174A
Authority: US
Inventors: Y Osawa; K Ueno
Original assignee: Teikoku Hormone Manufacturing Co Ltd
Current assignee: Aska Pharmaceutical Co Ltd
Priority date: 1971-09-20
Filing date: 1971-09-20
Publication date: 1973-09-18
Anticipated expiration: 1990-09-18

Abstract

Imidazole derivatives represented by the general formula :

WHEREIN R is a member of group consisting of alkyl group of one to four carbon atoms and aryl group, and R'' is a member of alkylene group of one to six carbons and a process for the preparation thereof.

Description

United States Patent 1 Osawa et al.

[111 3,759,946 1451 Sept. 18, 1973 l-ARYLOXY-4,5-DIPHENYLIMIDAZOLES [75] Inventors: Yoshio Osawa, Yokohama; Koitiro Ueno, Kawasaki, both of Japan [73] Assignee: Teikoku Hormone Mfg. Co., Ltd.,

Tokyo, Japan [22] Filed: Sept. 20, 1971 [21] Appl. No.: 182,174

Related U.S. Application Data [63] Continuation of Ser. No. 708,203, Feb. 26, 1968,

OTHER PUBLICATIONS Beak et al. J. Amer. Chem. Soc. Vol. 89, pages 2,375-2,384 (1967, May 10, 1967). Burger Medicinal Chemistry 2nd Ed. pages 518-519, N.Y., lnterscience, 1960.

Primary Examiner-Natalie Trousof AttorneyE. F. Wenderoth et a1.

[57] ABSTRACT Imidazole derivatives represented by the general formula wherein R is a member of group consisting of alkyl group of one to four carbon atoms and aryl group, and R is a member of alkylene group of one to six carbons and a process for the preparation thereof.

10 Claims, 7 Drawing Figures PAIENTEDSEPY 8mm 3; 759.946

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l-ARYLOXY-4,S-DIPHENYLIMIDAZOLES This is a continuation of U.S. Pat. application Ser. No. 708,203, filed Feb. 26, 1968 now abandoned.

This invention relates to novel and useful 1- alkoxyalkyl-, and l-aryloxyalkyl-4,5- diphenylimidazoles and acid addition salts thereof, as well as to the processes for their preparation. The compounds of the invention as free base can be represented by the general formula (1) below:

C6H5C-N in which R. stands for an alkylene group of one to six carbons, preferably a group represented by the formula -(CH n being an integer of one to four; and

R stands for an alkyl group of one to four carbons such as methyl or ethyl, or an aryl group such as phenyl. The compounds within the scope of the above formula (1) are all novel. We have successfully reacted 4,5-diphenylimidazole (hereinafter may be referred to as DPI) which has been obtained by conventional practices with alkoxyalkylhalide or aryloxyalkylhalide to produce the corresponding l-alkoxyalkyl-, and 1- aryloxyalkyl-DPI. We furthermore discovered that thus obtained compounds are very useful for prevention and medical treatment of allergic diseases, and that they also possess the properties required to medicines and cosmetics such as good lipophilic property and solubility.

The reaction performed in this invention can be represented by the formulae below.

wherein X stands for halogen such as chlorine or bromine, and R and R stands for the above-defined significance. The reaction is completed upon removal of the hydrogen halide formed, by any suitable means such as use of an acid binder. Because DPI (II) is a base itself, it can serve also as a dehydrohalogenation agent. Accordingly, the object compounds can be obtained simply by heating DPl together with halide (ill) to temperatures ranging 50 250 C. Whereas, it is of course permissible to perform the reaction, employing other suitable dehydrohalogenation agent such as triethylamine, dimethylaniline, and the like. Also an inert organic solvent may be optionally present in the reaction system. For example, a mixture consisting of DH, a halide and a suitably added dehydrohalogenation agent may be heated, and with progress of the reaction, the system takes a form of a homogeneous solution. The reaction likewise smoothly progresses in the presence of a suitable solvent which does not directly participate in the reaction, for example, ethers such as dioxane; aromatic hydrocarbons such as toluene or tetraline; ketones such as acetophenone; amides such as dimethylacetamide; a tertiary amine such as dimethylaniline;

sulfone compounds such as dimethylsulfoxide. When such organic solvents are used, the temperature range within which the reaction system is boiled under reflux at atmospheric pressure is preferred, while it is also possible to perform the heating reaction in a sealed tube. Generally preferred reaction temperature ranges 120 230 C.

The acid addition salts of l-alkoxyalkyland laryloxyalkyl-4,5-diphenylimidazoles are obtained by mixing a solution of l-alkoxyalkylor l-aryloxyalkyl- 4,5-diphenylimidazole prepared according to the abovementioned method in situ or after isolation of the free base, with an inorganic acid such as hydrohalogenie acid and phosphoric acid, an aliphatic acid such as acetic acid, propionic acid, tartaric acid, citric acid and succinic acid or an aromatic organic acid such as toluene sulfonic acid, salicylic acid and benzoic acid, and recrystallizing the solution from a solvent.

These acid addition salts are soluble in water and therefore useful as components of medicines and cosmetics, and free l-alkoxyalkyland l-aryloxyalkyl-4,5- diphenylimidazoles also possess high solubility in aqueous solvents and organic solvents. Therefore, they are also applicable to lipophilic cosmetics such as cold cream. In case they are used as components of medicines, they are compounded in an amount medically effective per dose (0.1 100 mg) with a carrier conventionally used for the manufacture of medical tablets such as lactose, starch, talc and magnesium stearate, and the mixtures are manufactured into medicines in the various forms which are effective for curing medicine eruption, urticaria, bronchial asthma, allergic naso-inflammation and the like.

Further, in case the lipophilic or hydrophilic compounds of this invention are used in the field of ms metic manufacturing, those cosmetics will be in relief of treatment for contagious dermatitis, make-up eruption and the like, and they are prepared by compounding the said lipophilic or hydrophilic compounds in an amount of 0.01 10 percent by weight with a conventional cold cream base comprising stearic acid, dehydrated lanolin, fluid paraffin, triethanolamine, glycerin and perfume, or comprising beeswax, solid paraffin, vaseline, fluid paraffin, borax and perfume, or with a vanishing cream base such as comprising stearic acid, sorbitan monostearate, polyoxyethylsorbitan monostearate, percent sorbite solution and perfume.

FIGS. 1 7 show infrared absorption spectra of chloroform solutions of the compounds obtained in accordance with the present invention.

The solubilities of some of the novel compounds obtained in accordance with the subject process in various solvents are shown in Table l, in comparison with the solubilities of DPI and l-( 2-oxyethyl)-4,5- diphenylimidazole which are known to have the dc scribed type of biological activity. It is clearly demonstrated by the data of Table 1 that because the compounds of the invention possess excellent solubilities compared with the known compounds, they can be advantageously used in pharmaceutical or cosmetic manufacturing. They can be used for cosmetics in such forms as solution, emulsion and cream, or as medicines in the various suitable forms.

Also the comparison of Magnus' activity as a norm of biological activity as in Table 1 reveals that the compounds of the invention possess the activity of substantially equal level to that of DP], and higher activity level than known 1-(2-oxyethyl)-4,5-diphenylimidazole. Heretofore, DPI could be found in difficulty to be used as medicines and cosmetics in spite of its desirable biological activity, because of its extremely low solubility. Thus the practical value of the compounds of this invention is very high.

Weight (g of hy- Weight; Weight drochlo- (grams) (grams) ride soluble soluble soluble in 100 in 100 in 100 m1. 01 ml. 01 ml. of Magnus Compound ether ethanol water activity DPI 0. 13 2. 38 0, 0012 1 CuH5- 0. 33 7. 77 5 0. 25 ClI5N dJH; H2011 C lI --N 2. 8 62 1O 0. 83 C H5-N C H; C Hz 0 C H3 CsH5- 50 50 0. 93 Calls-III CHzCHgOCHgCHa C H -N 10 20 5 0. 54 CHs-Il\ 0 H2O CH:

CrHs-- 10 50 10 0. 72 CsHs' I C H O C H; C H;

The magiifsaaivir "wafiiaasaiea as followsfsnifll specimens of small intestines excised of guinea pigs were suspended in Tyrode's solution maintained at 37 38 C., and the compounds obtained by the invention method was added to the solution, and succeedingly histamine was added to the solution to cause shrinkage thereof. Then, the degree of shrinkage was measured as the norm of biological activity of the sample. The values given in the table are the relative index numbers when the activity of DH was set to be 1.

Thus the present invention provides novel imidazole derivatives which exhibit high biological activities, and furthermore shows good affinity to various media and excellent absorbability.

The invention will be more specifically explained with reference to working examples which are given hereinbelow.

EXAMPLE 1 A sealed glass tube was charged with 22 g of DH, 19 g of 2-chloroethyl methyl ether, 21 g of triethylamine and 50 ml of dioxane, and was heated in an oil bath of 180 185 C, for 5 hours. Thereafter the system was cooled and the formed precipitates of hydrochloride of triethylamine was separated by filtration. The filtrate was poured in 2 liters of ice water, and thereupon formed crystalline product was filtered and dissolved in 100 ml of benzene. Hydrogen chloride was introduced to the benzene solution. Thereafter the solution was concentrated to yield 19.8 g of hydrochloride of l-(2- methoxyethyl)4,5-diphenylimidazole, in the form of colorless crystal. The product showed a melting point of 217 C. with decomposition and its elementary analysis values were as follows:

C: 68.92 percent; H: 5.93 percent; N: 8.90 percent (Calculated values as c n omucl are as follows:

C: 68.69 percent; H: 6.09 percent; N: 8.90 percent) Two grams of this hydrochloride was dissolved in 10 ml of water, and to the solution 10 ml of 4N aqueous caustic soda was added. The system was then extracted with 50 ml of other-benzene (1:1) mixed solvent, and the extract was dried with anhydrous potassium carbonate. Distilling off the remaining solvent, 1.5 g of oily 1-(Z-methoxyethyl)-4,5-diphenylimidazole was obtained as the residue. When crystallized from hydrous ethanol, 1.4 g of the imidazole compound containing one molecule of crystal water was obtained in colorless crystal. The product showed a melting point of 82 85 C. and its analytical values were as follows:

C: 72.68 percent; H: 6.66 percent; N: 9.72 percent. (Calculated values as C H ON,-H,O are as follows:

C: 72.95 percent; H: 6.80 percent; N: 9.45 percent) The infrared spectrum of the product is shown in FIG. 1.

EXAMPLE 2 Forty-four g of DPI, 38 g of 2-chloroethyl methyl ether and 42 g of triethylamine were added to 500 ml of tetraline, and the system was boiled under reflux for 40 hours. Cooling the system, the formed precipitate of hydrochloride of triethylamine was separated by filtration. The precipitate was washed with tetraline, and the washings were combined with the previously obtained filtrate. Thus combined washings of tetraline solution was extracted three times with each ml of 6N hydrochloric acid. The pH of the hydrochloric acid extract was adjusted to 8 by the addition of aqueous caustic soda. Thereupon an oily substance was separated, which was subsequently extracted with 500 ml of benzene. To the extract, 50 g of anhydrous sodium sulfate and 10 g of activated carbon was added, and was shaken for a short period and filtered. Distilling off the solvent from the filtrate and drying the residue, 40 g of light yellow, oily substance of l-(2-methoxyethyl)-4,5- diphenylimidazole was obtained. By crystallizing the same from hydrous ethanol, 38 g of a colorless crystalline product containing one molecule of crystal water was obtained, which showed a melting point of 80 84 C.

EXAMPLE 3 A sealed glass tube was charged with 44 g of DH and 10.5 g of Z-chloroethyl ethyl ether, and was heated in an oil bath of 210 215 C. for 6 hours. After cooling, the reaction product was dissolved in 200 ml of methanol, and poured into 2 liters of 1N aqueous caustic soda. Thus precipitated crystal was separated by filtration and dried. The filtrate was extracted with 200 ml of benzene, and the extract was washed with water and dried. Thus dried product was combined with the previously filtered and dried crystal, to be together boiled under reflux for an hour. Cooling the system, the crystalline substance was filtered, washed with 100 ml of benzene and dried. Thus 21.9 g of DPI was recovered. The filtrate and washings were combined-and concentrated, and thereafter refined by means of gradient chromatography employing a column packed with 250 g of neutral alumina and a solvent system of benzene and benzene-ethanol (1:1). The refined product was dissolved in a mixed solvent consisting of 100 ml of benzene and ml of methanol, and hydrogen chloride was introduced to the solution. Concentrating the solution by heating 16.2 g of hydrochloride of l-(Z-ethoxyethyl) 4,5-diphenylimidazole was obtained as colorless crystal. The product had a melting point of 183 185 C., and its elementary analysis values were as follows:

C: 69.42 percent; H: 6.48 percent; N: 8.51 percent. (The calculated values as C l-l oNyl-lCl are as follows:

C: 69.41 percent; H: 6.44 percent; N: 8.52 percent) The infrared spectrum of the free base of product is shown in FIG. 2.

EXAMPLE 4 A sealed glass tube was filled with 22 g of DH, g of Z-chloroethyl ethyl ether and 21 g of triethylamine together with 50 ml of dioxane, and was heated in an oil bath of200 205 C. for 10 hours. After cooling off the system, the formed precipitates of hydrochloride of triethylamine was filtered to remove, and the filtrate was poured into 2 litre of ice water. The supernatant liquid was discarded, and the remaining oily substance was dissolved in a mixed solvent composed of 100 ml of benzene and 5-ml of ethanol. After hydrogen chloride was introduced to the solution, the system was concentrated by heating. 23 g of l-(2-ethoxyethyl)-4,5- diphenylimidazole as colorless crystal was obtained. This product was identical with the product of Example 3.

EXAMPLE 5 A sealed glass tube was filled with 22 g of DH, 30.6 g of 2-bromoethyl ethyl ether and 21 g of triethylamine, together with 100 ml of dioxane. The tube was then heated in an oil bath of 190 200 C. for 5 hours. Then the system was cooled and the formed precipitates of hydrobromide of triethylamine precipitated was removed by filtration. The filtrate was poured in 2 liters of ice water, and extracted with 500 ml of benzene. The extract was washed in water, dried and dissolved in 5 ml of methanol. Hydrogen chloride was introduced to the solution, and thereafter the solution was concentrated by heating. Thus 12.05 g of hydrochloride of l- (2-ethoxyethyl)-4,5-diphenylimidazole, the identical product to that of Example 3, was obtained.

EXAMPLE 6 Twenty-two g of DH, 21 g of Z-chloroethyl ethyl ether, and 21 g of triethylamine were added into 200 ml of tetraline, and the system was boiled under reflux for 30 hours. After cooling the system, the formed precipitates of hydrochloride of triethylamine was filtered off. The filtrate was added with 1 g of anhydrous sodium carbonate, and then, tetraline was removed by steam distillation. The remained liquid was extracted with 300 ml of benzene, and the benzene solution was dried with anhydrous sodium sulfate. Thus dried system was dissolved in 10 ml of methanol, and hydrogen chloride was introduced to the solution. Concentrating the solution by heating, 22.1 g of hydrochloride of l-(Z- ethoxyethyl)-4,5-diphenylimidazole, the identical product with that of Example 3, was obtained.

6 EXAMPLE 1 Twenty-two g of DH, 20 g of 2-chloroethyl ethyl ether and 21 g of triethylamine were added to ml of acetophenone, and the system was boiled under reflux for 16 hours. After cooling the system, the formed precipitates of hydrochloride of triethylamine was separated by filtration and washed with a minor amount of dioxane. The filtrate and washings were combined and added with 10 g of sodium carbonate, then acetophenone was removed by steam distillation. Thereafter the system was extracted with 400 ml of benzene, and the benzene solution was dried with anhydrous sodium sulfate, followed by concentration until the system was reduced to 100 ml in quantity. Thus concentrated solution was added with 10 ml of methanol, and hydrogen chloride was introduced to the solution. Further concentrating the system by heating, 15.3 g of hydrochloride of I-(Z-ethoxyethyl)-4,5-diphenylimidazole, the product identical with that of Example 3, was obtained.

ether and 21 g of triethylamine were added to ml of N,N-dimethylacetamide, and the system was boiled under reflux for 15 hours. After cooling the system, the formed precipitates of hydrochloride of triethylamine was filtered off. The filtrate was concentrated to 50 ml at a reduced pressure, and poured into 1 liter of ice water. The supernatant liquid was discarded, and the remaining oily substance was dissolved in a mixed solvent composed of 200 ml of benzene and 30 ml of methanol. The solution was concentrated to 100 ml and left to stand. Thereupon formed crystal was filtered, thus allowing recovery of 7.7 g of DPI. After introducing hydrogen chloride to the filtrate, the filtrate was concentrated by heating 4.4 g of hydrochloride of l-(2-ethoxyethyl)-4,5-diphenylimidazole was obtained. This was the product identical with that of Example 3.

' "Ennis; Twenty-two g of DH and 20 g of 2-chloroethyl ethyl ether were added to 50 ml of dimethylaniline, and the system was boiled under reflux for 8 hours. Then 20 m1 of water and 5 g of caustic soda were added thereto,

and the system was distilled by steam to remove di-' methylaniline. The oily substance separated from the remaining liquid was extracted with 500 ml of benzene. The extract was washed in water, dried and concentrated to the volume of 100 ml. Hydrogen chloride was introduced to the concentrated liquid. Then concentration by heating was further continued, and 4.2 g of hydrochloride of l-(2-ethoxyethyl)-4,5- diphenylimidazole was obtained. This product was identical with that of Example 3.

EXAMPLE l0 Twenty-two g of DH, 20 g of Z-chloroethyl ethyl ether, and 24 g of dimethylaniline were added to 50 ml of dimethylacetamide,and the system was boiled under reflux for 8 hours with nitrogen stream. To the reacted liquid, 10 g of anhydrous sodium carbonate was added and then steam distillation was performed. The remained liquid was extracted with 400 ml of benzene, and the extract was dried with anhydrous sodium carbonate. After introducing hydrogen chloride to the dried benzene solution, the solution was concentrated 7 by heating. Thus 3.4 g of hydrochloride of l-(2-ethoxyethyl)-4,5-diphenylimidazole, the product identical with that of Example 3, was obtained.

EXAMPLE 11 A sealed glass tube was charged with 1 1 g of DH, 8.1 g of chloromethyl methyl ether and 10 g of triethylamine together with 50 ml of dioxane. The tube was then heated in an oil bath of 160 165 C. for 6 hours. After cooling, the formed precipitate was removed from the system by filtration. The filtrate was poured in 1 liter of ice water, and extracted with 200 ml of benzene. The extract was washed in water, and dried with anhydrous sodium carbonate. Five ml of methanol was added to the dried benzene solution, and hydrogen chloride was introduced to the solution. Subsequently the solution was concentrated by heating, to yield 3.15 g of hydrochloride of l-methoxymethyl-4,$- diphenylimidazole was obtained. The product showed a melting point of 188 191 C., and its elementary analysis values were as follows:

C: 67.97 percent; H: 5.57 percent; N: 9.08 percent (The calculated values as C,-,1-l ON,-HC1 are as fol-' lows:

C: 67.89 percent; H: 5.70 percent; N: 9.31 percent The infrared spectrum of the free base of the product is shown in H6. 3.

EXAMPLE 12 A sealed glass tube was charged with 11 g of DP] and 9.5 gof chloromethyl ethyl ether, and heated in an oil bath of 200 210 C. for hours. After cooling off, the content of the tube was poured into one liter of 1N aqueous caustic soda, and extracted with 500 ml of benzene. After the extract was dried with g of potassium carbonate, the solvent was distilled. The residue was refined by gradient effluent chromatography employing a column packed with 200 g of silica gel and an elute solvent system comprising of 2 liters of benzene and 300 ml of benzeneethanol (1:1) mixed solvent. Hydrogen chloride was introduced to the benzene solution of the refined product, and the solution was concentrated. 1.19 g of the object product, l-ethoxymethyl- 4,5-diphenylimidazole was obtained as colorless crystal. The product showed a melting point of 236 240 C., and its elementary analysis values were as follows:

EXAMPLE 13 A sealed glass tube was charged with 22 g of DPl and 7.9 g of 2-chloroethoxybenzene, and heated in an oil bath of 210 220 C. for 5 hours. After cooling off, the reaction product was dissolved in 500 ml of benzene, and extracted with 300 m1 of 6N hydrochloric acid. The extract was made alkaline with an aqueous caustic soda, and further extracted with 300 ml of benzene. Then the system was refined by means of gradient effluent chromatography employing a column packed with 200 g of silica gel and a solvent system composed of 2 liters of benzene and 400 ml of benzene-ethanol (1:1) mixed solvent, After introducing hydrogen chloride to a benzene solution of the refined product, the solution was concentrated. Thus 400 mg of hydrochloride of l- (2-phenoxyethyl)-4,5-dipehnylimidazole was obtained as colorless crystal. The product showed a melting point of 203 205 C., and its elementary analysis values were as follows:

C: 73.37 percent; H: 5.72 percent; N: 7.31 percent (The calculated values as C,,H,,,ON,-l-1Cl are as follows:

C: 73.30 percent; H: 5.58 percent; N: 7.44 percent) The infrared spectrum of the free base of the product is shown in FIG. 5.

EXAMPLE l4 Eleven g of DH, 19.6 g of l-bromo-6- methoxyhexane and 11 g of triethylamine were put in a sealed glass tube together with 50 ml of dioxane, and heated in an oil bath of C. for 5 hours. After cooling, the formed precipitates of hydrobromide of triethylamine was removed by filtration. The filtrate was poured into 2 liters of water, and extracted with 1.2 liters of 3:2 benzene-ethyl acetate mixed solvent. The extract was washed in water, dried, and removed of the solvent by distillation and further dried to solid state. The solid residue was refined by means of gradient effluent chromatography employing a column packed with 200 g of alkaline alumina and a solvent system composed of 2 liters of benzene and 400 ml of 1:1 benzene-ethanol mixture. Hydrogen chloride was introduced to a benzene solution of the refined product, and the solution was concentrated to a total volume of 20 ml. Upon addition thereto of 10 ml of hexane, 3.4 g of hydrochloride of 1-(6-methoxyhexyl)-4,5- diphenylimidazole was obtained. The product showed a melting point of 116 119 C., and its elementary analysis values were as follows:

C: 71.05 percent; H: 6.87 percent; N: 7.25 percent (The calculated values as c,,H,,0N,-Hc1 are as follows:

C: 71.24 percent; H: 7.07 percent; N: 7.55 percent) The infrared spectrum of the free base of the product is shown in FIG. 6.

EXAMPLE l5 Eleven g of DH, 16.7 g of l-bromo-4-methoxybutane and 1 1 g of triethylamine were put in a sealed glass tube together with 50 ml of dioxane, and heated in an oil bath of 190 210 C. for 5 hours. After cooling off, the formed precipitates of hydrobromide of triethylamine was filtered. The filtrate was poured in 2 liters of water, and extracted with a liquid mixture composed of 1 liter of benzene and 200 ml of ethyl acetate. The crude product obtained from the extract from which the solvent had been distilled off, was refined by means of gradient effluent chromatography employing a column packed with 200 g of silica gel, 2 liters of benzene and 400 ml of 1:1 benzene-ethanol mixture. Hydrogen chloride was introduced to a benzene solution of the refined product. Thereafter hexane was added to the solution. Thus 4.2 g of hydrochloride of l-(4- methoxybutyl)4,5-diphenylimidazole was obtained as colorless crystal. The product had a melting point of 151 154 C., and its elementary analysis values were as follows:

C: 70.13 percent; H: 6.47 percent; N: 8.43 percent (The calculated values as C,,,H,,ON,-HC1 are as follows:

C: 70.06 percent; H: 6.76 percent; N: 8.17 percent) The infrared spectrum of the free base of the product is shown in FIG. 7.

EXAMPLE 16 Two g of l-(2-methoxyethyl)-4,5-diphenylimidazole and l g of salicylic acid were dissolved in 20 ml of ether, and the solvent was distilled off. The residue was recrystallized from methanol to obtain 1.2 g of salicylate. The product showed a melting point of 76 80 C., and its elementary analysis values were as follows:

C: 69.35 percent; H: 6.21 percent; N: 6.74 percent (The calculated values as C H N,-C l-l,0,'l-l,O are as follows:

C: 69.11 percent; H: 6.03 percent; N: 6.45 percent) EXAMPLE l7 l-(2-Methoxyethyl)-4,5-diphenylimidazole (2.2) g and 0.6 g of acetic acid were mixed together, and the so obtained oil substance was recrystallized from methanol to obtain 1.3 g of the crystalline acetate. The product showed a melting point of 67 71 C., its elementary analysis values were as follows:

C: 74.32 percent; H: 7.40 percent; N: 8.89 percent (The calculated values as C H,,ON,-C,H O,-H,O are as r C: 74.04 percent; H: 7.46 percent; N: 8.64 percent) EXAMPLE 18 wherein R is alkyl of one to four carbon atoms or phenyl and R is alkylene of one to six carbon atoms; and

a pharmaceutically effective acid addition salt thereof.

2. A compound according to claim 1 wherein R is alkylene of one to four carbon atoms.

3. A compound according to claim 1 said compound being l-(2-ethoxyethyl)-4,5-diphenylimidazole.

4. A compound according to claim 1 said compound being I-(Z-methoxyethyl)-4,5-diphenylimidazole.

5. A compound according to claim 1 said compound being l-(ethoxymethyl)-4,5-diphenylimidazole.

6. A compound according to claim 1 which is a pharmaceutically acceptable salt with an acid selected from the group of hydrohalogenic acids, phosphoric acid, aliphatic carboxylic acids and aromatic organic acids.

7. A compound according to claim 6 which is a salt of a hydrohalogenic acid.

8. A compound according to claim 6 which is a salt of an acid selected from the group consisting of acetic acid, toluene sulfonic acid and salicylic acids.

9. A compound according to claim 1 which is an acid addition salt of l-(2-ethoxyethyl)-4,5- diphenylimidazole with an acid selected from the group consisting of hydrohalogenic, acetic, toluene sulfonic and salicylic acids. 4

10. A compound according to claim 1 which is an acid addition salt of l-(2-rnethoxyethyl)-4,5- diphenylirnidazole with an acid selected from the group consisting of hydrohalogenic, acetic, toluene sulfonic and salicylic acids.

Claims

2. A compound according to claim 1 wherein R'' is alkylene of one to four carbon atoms.
3. A compound according to claim 1 said compound being 1-(2-ethoxyethyl)-4,5-diphenylimidazole.
4. A compound according to claim 1 said compound being 1-(2-methoxyethyl)-4,5-diphenylimidazole.
5. A compound according to claim 1 said compound being 1-(ethoxymethyl)-4,5-diphenylimidazole.
6. A compound according to claim 1 which is a pharmaceutically acceptable salt with an acid selected from the group of hydrohalogenic acids, phosphoric acid, aliphatic carboxylic acids and aromatic organic acids.
7. A compound according to claim 6 which is a salt of a hydrohalogenic acid.
8. A compound according to claim 6 which is a salt of an acid selected from the group consisting of acetic acid, toluene sulfonic acid and salicylic acids.
9. A compound according to claim 1 which is an acid addition salt of 1-(2-ethoxyethyl)-4,5-diphenylimidazole with an acid selected from the group consisting of hydrohalogenic, acetic, toluene sulfonic and salicylic acids.
10. A compound according to claim 1 which is an acid addition salt of 1-(2-methoxyethyl)-4,5-diphenylimidazole with an acid selected from the group consisting of hydrohalogenic, acetic, toluene sulfonic and salicylic acids.