CH536293A - 7-alpha methyl-17-alpha ethinyl oestradiol-3-cyclopentyl - ether oestrogenic uterotro - Google Patents

Abstract

7 Alpha-methyl-17 alpha-ethinyl-oestradiol-3-cyclopentyl ether, oestrogenic, uterotropic, fertility regulator. Title cpds. of formula may be prepd. by reacting 3-cyclopentyloxy-7alpha-methyl-17-oxo-DELTA1,3,5(10)-oestratriene with a metal acetylide (e.g. Na, K or Li) or an acetylenic Grignard reagent, or by etherifying 7alpha-methyl-ethinyl-oestradiol with cyclopentanol or its reactive deriv. The cpd. hs oestrogenic, uterotropic and blastocyte implantation inhibiting activity.

Description

       

  
 



   The present invention relates to a process for the preparation of the 3-cyclopentyl ether of 7-methyl-17x-ethinyl-oestradiol of the formula
I.
EMI1.1

This compound has valuable pharmacological properties. It has an estrogenic, uterotropic and / or blastocyte implantation-inhibiting effect. It shows e.g. an estrogenic effect after a single oral amplification in the vaginal keratinization test on female rats at doses of 0.03 to 10 mg / kg. The uterotropic efficacy can be demonstrated in the female rat after a single oral application of doses of 0.1 to 3 mg / kg.

  The blastocyte-implantation-inhibiting property can be demonstrated in normal rats after copulation with a single oral dose of 0.01 to 0.03 mg / kg and the disturbance of the vaginal and ovulatory cycles of the female rat with a single oral administration of 1 mg / kg remedy. The new compound can thus be used as an estrogenic agent and for controlling fertility.



   The new compound of the formula I is obtained when, according to the invention, a compound of the formula
EMI1.2
 etherified in the 3-position with cyclopentanol or an ester thereof. This is usually done by adding the compound of formula II or a salt thereof, e.g. the sodium or potassium salt with a reactive ester of cyclopentanol, optionally in the presence of a basic catalyst such as sodium or potassium carbonate, hydroxide or alcoholate, e.g. -methoxide or -ethanolate converts.

  The reactive esters used are preferably those with strong inorganic or organic acids, such as hydrohalic acids, in particular hydrochloric or hydrobromic acid, sulfuric acid or an organic sulfonic acid such as methane, ethane or an optionally substituted benzenesulfonic acid, primarily the benzenesulfonic acid itself, p " Chlorobenzenesulfonic acid or p-toluenesulfonic acid.This reaction is carried out in a customary manner, for example in a solvent such as an alcohol, e.g.



  Methanol, ethanol, or propanol, an ether such as di-lower alkyl glycols or dioxone, or mixtures of these with water.



   The starting material of the formula II is known:
The novel compound obtainable according to the invention can be used as a medicament in the form of pharmaceutical preparations which combine this compound with pharmaceutical, organic or inorganic, solid or liquid carriers which are suitable for enteral, in particular oral or parenteral administration. Those substances that do not react with the new compound come into question for the formation of the same. The pharmaceutical preparations can be in solid or liquid form. They may contain auxiliaries, such as preservatives, stabilizers, wetting agents or emulsifiers, salts to change the osmotic pressure or buffers. They can also contain other therapeutically valuable substances. The pharmaceutical preparations are obtained according to the usual methods.



   The new compound of formula I can also be used in veterinary medicine e.g. in one of the forms mentioned above, or in the form of feed or additives for animal feed. For example, use the usual extenders and thinners or feed.



   In the following example the temperatures are given in degrees Celsius.



   Example 3.00 g of 3.17,, 8 - dihydroxy -7x-methyl-170c-ethinyl-Al 3 - 5 (10) -estratriene (7cG-methyl-ethinylestradiol) are in
100 ml of absolute alcohol dissolved and slowly added dropwise to a stirred suspension of 2.0 g of potassium carbonate in 3.0 g of cyclopentyl bromide. The mixture is then refluxed with stirring for 24 hours. It is then cooled to room temperature, the insoluble components are filtered off, the solution is diluted with water while stirring, the precipitated product is filtered off with suction, washed neutral with water, dried and chromatographed on silica gel.

  By evaporation of the toluene and toluene-ethyl acetate eluates and crystallization of the residue obtained from ether / hexane, the pure 3-cyclopentyloxy-70c-methyl-17cc-ethinyl-170-hydroxy-61.3,5'10 'estratriene, which melts at 121-1220 won.



   = + = (Chloroform).


    

Claims (1)

PATENT CLAIM Process for the preparation of a new, highly estrogenically active 3-cyclopentyloxy steroid, characterized in that the 3,17-dihydroxysteroid of the formula EMI2.1 etherified in the 3-position with cyclopentanol or an ester thereof. SUBClaim Process according to patent claim, characterized in that the etherification is carried out by means of a reactive ester of cyclopentanol in the presence of a basic catalyst.