IL26936A - 3-(2'chloroethoxy)-17alpha-ethynyl-17beta-hydroxy-delta1,3,5(10)-estratriene and process for the preparation thereof - Google Patents

Description

C O H E N Z E D E K S P I S B A C H R E G PAT E N T AT T O R N E YS LEVONTIN 1 T E L A V V P A T E N T S D E S I G N S O R D I N A N C E SPECIFICATION E3TRATRIENE PROCESS FOR THE PREPARATION THEREOF an Italian Joint Stock of Largo DO HEREBY DECLARE the nature of this invention and in what manner the same is to be performed to be particularly described and ascertained in and by the following The invention provides as a new compound a new halogenated of the estrane series and a proces s for its The new compound of the invention is l which has the According to the process of the invention is prepared starting from which is first treated with a compound able to introduce the ethoxy group into the by and then made to react with the chloride of a sulphonic acid and subs equently with lithium chloride to obtain the corresponding 17 is treated with generally in a solution of an alkali metal such as potassium or lithium in a tertiary Excess reagent is removed by addition of alkali and the compound obtained is s eparated and crystallized from a solvent such as diethyl ether acetone or from their mixtures with petroleum generally dis s olved in a bas e such as pyridine or chloroform containing small amounts of is treated with the chloride of a sulphonic acid such as methansulphonic benzensulphonic and sulphonic acid at from to The product may then be extracted with a solvent which is evaporated off under reduced pres sure and the sulphonate obtained is refluxed with lithium chloride in a polar solvent such as a lower aliphatic alcohol and extracted with an organic solvent The residue of the organic layer is purified by crystallization from a s olvent such as diethyl acetone or from their mixtures with or methylene dichloride or by The new compound of the invention is white soluble in chlorinated solvents such as methylene dichloride and ethyl The new compound of the invention is noted for its high estrogen activity and s o is in human field as ovulatory particularly suitable for oral and in veterinary field particularly for s exual stimulation in the females of the domestic animals and as coadjuvant in the treatment of certain infections of the female genital apparatus The new compound of the invention can be administered by either the subcutaneous or oral Although it is not esterified with long chain fat acids it shows a prolonged effect with duration proportional to Like all estrogens the new compound of the invention is endowed with i in comparis on to which the new compound of the TABLE 1 The effective minimum dose is the amount of the active substance able to give 2 out of 3 of the treated animals a proestric stimulation the vaginal epithelium or to provoke the estrus in 1 out of 3 treated As is shown in Table in absolute less active than by the subcutaneous route as its activity appears at the dose of 3 instead of g for the standard However it has the same activity as when administered by the oral minimum dose for Above all it is noted that has a prolonged effect by the subcutaneous route which is proportional to the injected At the same dosages as the standard it shows a clearly prolonged Antiovulatory activity has been tested in the adult female rat with a regular cycle and daily treated for a whole cycle at the end of which the ovary tubes have been examined in order to establish the presence of a good antiovulatory effect both by the subcutaneous route and especially by the oral In Table 2 are reported the data of calculated for both the subcutaneous and oral administration of the new compound of the invention and of the Compound Administration 1 subcutaneous ethyny 1 1 dr oxy oral subcutaneous oral 30 The effective dose is the amount of active substance able to produce the desired effect on of treated Antigonadotrophic activity has been studied by using the technique of the parabiosis in the impuberal rat male untouched iene by subcutaneous administration has shown ED50 while by oral administration In the veterinary field is indicated in all those cases in which in the females of the domestic animals a sexual stimulation is equired due to an incomplete functional conditions or particular individual It is successfully employed in the treatment of the various forms of pyometritis in which a lively reactivation of the genital apparatus circulation or the expulsion of the pathological material from the uterus is To this purpose the compound of the invention can be also employed in female having normal but affected by purulent fi to illustrate preparation of the A comparison was made between the activity of ether EHE is three times more active than EE3ME in the vaginal smear test carried out on the female castrated both by subcutaneous and oral The minimal effective dose of EHE is 3 ug for both these routes of as compared with 10 ug of The following Example serves to illustrate preparation of the new compound of the EXAMPLE 3 To a solution of 80 of sodium in 10 cc of tert amylic alcohol g of ethynylestradiol and g of are added and the mixture thus obtained is refluxed and stirred for After cooling to room temperature 50 cc of a 5N sodium hydroxide solution are added and the mixture is stirred for 15 Then the mixture is extracted three times with ethyl acetate and the organic after washing to are dried over anhydrous sodium sulphate and evaporated under reduced pressure to The taken up with gives g of 1 estratriene melting at g of this product are dissolved in 25 cc of anhydrous The solution is cooled with cc of chloride is added and allowed to stand over night at The mixture is poured into extracted with methylene washed until neutral with water and dried over anhydrous sodium The solvent is evaporated under reduced pressure and the which weighs g is dissolved in 120 cc of 5 g of lithium chloride are added and the mixture is refluxed for 5 hours and then concentrated to small taken up with water and extracted with ethyl The organic layer is washed with water until neutral and evaporated in vacuo to The residue dissolved in benzene is passed through 40 g of Florisil mesh magnesium and eluted with The insufficientOCRQuality

Claims (2)

1. HAVING particularly described and ascertained the nature of our said invention and in what manner the is to be we declare that what we claim A process for the preparation of with e ethylercarbonate the resulting is sulphonated organic with the chloride of and the resulting steroyl sulphonate is with lithium A process for the preparation of substantially as hereinbefore A process according to

2. Claim 2 substantially the Example 1 iene A pharmaceutical conposition suitable for use in the hunan or veterinary field containing 1 3 in admixture with a diluent or THIS 3rd day of COHEN SPISBACH for Applicants insufficientOCRQuality