Untitled record

The invention relates to a process for the preparation of anti-inflammatory aralkyl compounds of general formula I:

CH

X

Ar — CH (I) \

CH 1 wherein Ar represents a group selected from: 4-phenoxy-3-methoxyphenyl, 4-cyclooctylphenyl, 4'-fluorobiphenyl-4- (2-norbornyl) phenyl.

A process for the preparation of isop opilbenzene is known, by the interaction of monochlorizopropane on benzene, at the boiling temperature of the reaction mixture.

This process has the disadvantage that it requires an additional phase of obtaining the zopropylhalogenderivate from monohalogenpropane, which raises the manufacturing cost.

The process according to the present invention involves the ideas mentioned by.

of aralkyl compounds that a compound of general formula II is hydrogenated:

CH₃ /

Ar-C-OH (II) \

CH_S wherein Ar has the meaning shown above, with hydrogen gas in the presence of palladium catalyst and possibly sulfuric acid, in an organic solvent medium preferably ethyl acetate or ethanol, then the reaction product is separated by known methods.

An example of evil is given below¹⁵ Invention of the invention.

4- phenylcumen

5- hydrogenated a mixture of 21.2 de

2- (4-biphenylyl) ~ 2-propanol, 4 g of 5½ Pd /

4, 20 drops of SOdU and 2Q0 ml of ethyl acetate, until the calculated amount of hydrogen was absorbed. After the catalyst was separated by filtration, the reaction mixture was washed with water, with 5% NaHCO 3 solution again with water and then dried over sodium sulfate. Evaporation of the solvent in vacuo leaves a residue

LEI 2.20 OIL PRICE which, by distillation, gives 16.3 g of product with a boiling point of 100 ... 112 ° C / 0.09 mm! η ρ “+5849.

CisHiî analysis:

- calculated: C = 91.78; H, 8.22;

- Found: C, 92.06; H, 7.97.

according to the method of the example given The following compounds are also obtained:

3-methoxy-4-phenoxy cumene, with boiling point 138, 139 / 0.07 mm, n = 1.5602 from 2- (3-methoxy-4-phenoxyphenyl) -2-propanol.

Analysis C10H18O2:

- calculated: C = 79.31; H, 7.49;

Found: C, 79.47; H, 7.47.

4- (2-norbornyl) -cumen, boiling point

15O ... 156 ° C / 5 mm, n = 1.5333 of 2-hydroxy-2- (4-rumenyl) -orbornane.

Analysis: Cfolfo:

- calculated: C = 89.65; H, 10.35;

Found: C, 89.38; H, 10.20.

The unit of dedication of the compounds, fed by the thousands of them, is admiinteitoait to the sufijiccibuil who suffers from «to process fofitaimatoir, in doses from about 1.0 fe to about 100 mg / kg body dysfunction, daily either in a single dose or in divided doses. .

If divided doses are used, the anti-inflammatory agent is given every 4 or 6 hours. Since some of the anti-inflammatory substances used in practice do not possess analgesic activity, it is preferable to administer this agent in combination with another analgesic agent such as, for example, aspirin or d-proixifetlU'1, until swelling, sensitivity, decreased mobility begin. Give back Although oral administration is most preferable, anti-inflammatory agents may also be administered parenterally or rectally in the form of suppositories.

Since most of the compounds used are in an oily state, they can be absorbed into an inert carrier such as talc, silica gel, or the like, before being capsulated or transformed into tablets, pills, powders or granules. Those that are made for oral administration may also comprise other inert substances or diluents such as magnesium stearate etc. Tablets and pills can also be prepared with enteric coatings. These compounds may also be incorporated into soft gelatin capsules.

Liquid dosages for oral administration may comprise pharmaceutically acceptable forms such as emulsions, solutions, suspensions, syrups and elixirs containing commonly used inert diluents such as water or an appropriate oil.

In this form, it is preferable to dilute the agent to be formulated with a suitable oil such as: walnut oil, cottonseed oil, sesame oil or the like. These diluted mixtures comprise the internal phase of the emulsion. Sweetening and other sweetening agents or the like are also dissolved in water which acts as an external phase of the emulsion. In addition to inert diluents, these mixtures may also comprise other agents for humidification, emulsification and suspending, odorizing, sweetening and other agents.

Compositions for rectal or suppository administration should contain in addition to the active substance and an excipient, such as cocoa butter, or suppository wax.

The dosages of the active ingredient according to the invention may be varied, however, it is necessary that the amount of the active ingredient be such as to give an appropriate dosage. The dosage chosen depends on the desired therapeutic effect, the route of administration and the duration of treatment. Generally, the dosage levels are between 1 and 100 mg / kg of body weight, daily, in mammals, in order to achieve an effective withdrawal of inflammation or pain. However, the doses to be prescribed from one or more of these compounds in a convenient formulation range from about 5 to 1000 mg at a time. up to 4 times daily, depending on the body weight of the patient, the treatment conditions or other factors that the doctor must take into account.

The present invention has the advantage that it allows to widen the range of compounds with anti-inflammatory activity, which does not produce gastric side effects.