DE1695339B2 - 43-diphenylimidazole compounds - Google Patents

Description

CH

CH ₅ -CN

in which R denotes a hydrogen atom or the ethyl group.

The invention relates to 4,5-diphenylimidazole compounds.

4,5-Diphenylimidazole is, for example, from DT-AS 11 98 Ol 1 known. This 4,5-diphenylimidazole acts to expand the capillary vessels. It's in water Petrolatum, paraffinum liquidum and glycerin are almost insoluble, so that it is difficult to make this connection to be incorporated directly into a medicinal product in which the aforementioned products are used as the basis will. This situation can, for example, apply to an ointment for dermatitis treatment, toothpaste, Cosmetics such as cold bream, face milk, pad lotion or lipstick mass result, with the Insolubility of 4,5-diphenylimidazole in the above Materials has a detrimental effect as it is only dissolved in an organic solvent such as alcohol must be in order to be added to the base in this form.

The object of the invention was to change the 4,5-diphenylimidazole so that its basic advantageous properties such as easy absorption, capillary expansion and increase in blood and lymph circulation can be maintained without causing irritation even on sensitive skin can, on the other hand, the solubility in the materials mentioned compared to that of pure 4,5-diphenylimidazole is increased. At the same time it should be ensured that the improvement in properties of 4,5-diphenylimidazole does not have the disadvantage of increased toxicity.

This problem was solved by providing 4.5 diphenylimidazole compounds the general formula

H CH ₁

C-C-OH

/ I

CH ₅ -CN HR
CH

Il

CH ₅ -CN

in which R is a hydrogen atom or the ethyl group.

It has surprisingly been found that such a modified 4,5-diphenylimidazole has a higher solubility in the materials mentioned than pure 4,5-diphenylimidazole without the outstanding dermatological properties of 4,5-diphenylimidazole being impaired. The 4,5-diphenylimidazole compounds according to the invention show a strong antihistamine effect and have an expanding effect on the capillary vessels. While the water solubility as well as solubility in glycerol, liquid paraffin and petrolatum of 4,5-diphenylimidazole is very low both at 20 ⁰ C and at 7O ⁰ C, the solubility is in these materials both at 20 ° C and greatly increased at 7O ⁰ C (with the exception of Petrolaum, which is solid at 20 ⁰ C), see Table 1 below.

Table 1

- " Solvent substance
Dl DIPO DIPE (ml / 1 g) (ml /! β) (ml / 1 g : · ■> Distilled
water
20 C
70 C 300,000 ml
100,000 ml 9 760 ml
3 280 ml 10 500 ml
4,500 ml Glycerin
ⁱ⁰ 2OC
70 C 6 500 ml
4,500 ml 150ml
100 ml 300 ml
220 ml Liquid
paraffin
r, 20 C
70 C 8 500 ml
5 500 ml 1300 ml
500 ml 1000 ml
430 m! Petrolatum
20'C
70 C 8 700 ml 750 ml 600 ml

In the table, 4,5-diphenylimidazole is abbreviated as DI, while 1- (4,5-diphenylimidazolyl) -2-propanol is designated with DIPO and l- (4,5-diphenylimidazolyl) -2-ethyl-2-propanol was designated with DIPE.

Medicaments to which compounds according to the invention are added, for example dermatitis ointments, Effectively promote the peripheral blood circulation, strengthen the functions of the skin and increase the Absorption of active components of the ointment in the same way as pure 4,5-diphenylimidazole, and you can also use these compounds thanks to their anti-allergic and anti-inflammatory properties Rash to be cured.

To determine the toxicity of the 4,5-diphenylimidazole compounds according to the invention, 4,5-diphenylimidazole and 1- (4,5-diphenylimidazolyl) -2-propanol and 1- (4,5-diphenylimidazolyl) -2-ethyl 2-propanol dissolved or suspended in a suitable concentration in 1% aqueous gum arabic solution, and the test solution thus obtained b; Suspensi "-; was given orally to mice of DD ancestry ^ ^! Betw.

injected subcutaneously. The solutions or ouopensions were given to the mice in an amount of 0.1 ml to 0.15 ml per day for five consecutive days entered. The results obtained in these investigations are shown in Table 2 below compiled:

3 Table 2 16 95 339 Total dose
(mg / kg) 4th Death rate
(Death lane /
Total cases) Imiclazole compound 1500 mg 0/10 4,5-diphenylimidazole treatment 1500 mg 0/10 orally 1500 mg 0/10 1- (4,5-Diphenylimidazolyl) -2-propanol subcutaneous
injection 1500 mg 0/10 orally 1500 mg
1500 mg 0/10
0/10 M4,5-diphenylimidazolyl) -2-ethyl-
2-propanol subcutaneous
injection orally
subcutaneous
injection

example 1

75 g of propylene oxide and 5 ml of pyridine or triethylamine are added to 580 ml of 94% ethyl alcohol and mixed with 220 g of 4,5-diphenylimidazole. The whole thing is heated to a gentle boil in a water bath. The mixture is refluxed for 1.5 hours. The 4,5-diphenylimidazole dissolves completely. After cooling, the reaction mixture is kept at room temperature (20 ^° C.) for 10 hours. During this process, 1- (4,5-diphenylimidazolyl) -2-propanol crystallizes out in the form of colorless platelets. The crystals are suction filtered, washed with cold 40% alcohol and then dried at room temperature. 223 g of crystals (A) are obtained. They have a melting point of 165-166 ⁰ C. to 500 ml of the filtrate obtained during filtration with suction, 100 ml of water was added. The mixture is kept at room temperature for 10 hours. 15 g of crystals (B) are obtained . The melting point of these crystals is lower than that of the crystals (A). 10 g of the crystals (A) are mixed with 200 ml of distilled water and dissolved by adding 10 ml of 10% hydrochloric acid. The somewhat cloudy solution is mixed with 5 g of decolorizing charcoal and, after thorough shaking, filtered. The clear solution thus obtained is made alkaline by adding 28% strength aqueous ammonia solution. The precipitate is separated off in a vacuum filter and then dried at room temperature. The dried material is recrystallized from 80% ethanol. 8 g of purified crystals are obtained. These have a melting point of 167-168 ° C. The elemental analysis of the product showed:

dissolves completely. The reaction solution is then kept at room temperature (20 ^° C.) for 10 hours. During this process, 1- (4,5-diphenylimidazolyl) -2-ethyl-2-propanol crystallizes out in the form of colorless crystals. After filtering off the crystals obtained are with

Washed cold 40% ethanol and then dried at room temperature. The yield is 200 g of crystals (A). These have a melting point of 146 ° C. 100 ml of water are added to 500 ml of the filtrate. The mixture is kept at room temperature for 10 hours.

jo temperature held, whereby 20 g of crystals (B) are obtained. The melting point of these crystals (B) is lower than that of the crystals (A). The pure crystallized product with a melting point of 148-149 ° C. according to that described in Example 1 is obtained from these crystals

j-j cleaning process.

i C,% Calculated Found H, % 77.67 77.54 I. N,% 6.52 6.41 10.06 9.82 I. Example 2

Calculated Found ⁴⁰ C,%
H, %
N,% 78.40
7.24
9.14 78.21
7.40
9.40 ■ 1) Example 3

100 g 1,2-epoxy-2-methylbutane and 5 ml N-methylpiperidine or triethylamine are added to 580 ml of 94% ethyl alcohol. After adding 220 g 4,5-Diphenylimidazole, the mixture is heated to a gentle boil in a water bath. One heats up 1.5 hours under reflux. The 4,5-diphenylimidazole in a reflux condenser and dropping funnel two-necked flask provided 200 ml of ethanol, 70 g of 4,5-diphenylimidazole and 50 l-bromopropanol (2) brought in. Then a solution of 20.9 g of caustic soda in 80 ml of distilled water was poured in added dropwise through the dropping funnel for about 1 hour, the contents of the flask in a water bath was kept at a low boil. The reaction solution was filtered while hot, and the filtrate was kept at room temperature (20 ° C.) for 10 hours, during which time the product crystallized out. The crystals were filtered off with suction and washed with 40% ethanol and then with water. The yield

ho was a total of 59 g of crystals having a melting point of 152- 160 ⁰ C. To 140 ml of the filtrate from which the crystals had been separated off, 50 ml water were added. The whole was kept at room temperature for 10 hours, with an additional 5 g of crystals

hi incurred. The pure l- (4;> - diphenylimidazolyl) -2-propanol having a melting point of 167 -168 ⁰ C was obtained by workup of these crystals by the method described in Example 1 purification processes.

5 6

Crystals (AJ in Example 2 and solid the same as Example 4 crystals (B). By treating the filirate from which the

Crystals had separated in the same

: 1 3 was repeated, but instead of the manner as in Example 3, a further amount of) m-propanol (2) 46 g of 1-chloro-2-diethyl-butanol 5 5 g of crystals were obtained. The pure product with a nd, 55 g of crystals of 1- (4,5-diphenyl melting point of 148-149 ⁼ C was obtained by treatment) -2-ethyl-2-propanol. The development of the crystals according to that described in Example 1 have a lower melting point than the purification process.

Claims (1)

Claim: 4,5-diphenylimidazole compounds of the general formula H CH ₃ I i C-C-OH / I I C ₁ Hs-CN HR