DE1668611C - 3- (beta-diethylaminoethoxy) -16-oxo-delta high 1,3,5 (10) -estratriene, 3- (beta-diethylaminoethoxy) -17-oxo-delta high 1,3,5 (10) -lumi- estatriums and their chlorohydrates and processes for their preparation - Google Patents

Description

The invention relates to a process for preparing 3 - (^ Diäthylaminoäthoxy) -16-oxo-/ J ¹ - ^{3 's <I} °> -estratriene and Sf ^ -DiäthylaminoäthoxyJ-n-oxo-zl ¹ · ³ · ^{5' 10} ) -lumi-estatriene, in which the angular 13-methyl group is / is 9-oriented if the ring D has a keto function in the 16-position, and is «-oriented if the ring D has a keto function in the 17-position, as well as from pharmacologically acceptable salts of these compounds.

The compounds prepared according to the invention have valuable pharmacodynamic properties on. They show a considerable anti-lipemic effect, while they are completely without estrogenic effects.

The products, the 3 - (/? - diethylaminoethoxy) -16-oxo- ^{I> 3} - ^{5 <I0)} -estratriene and the 3 - (/ 7-diethylaminoethoxy) -17-oxo-I '■ ^{3> 5} < ¹¹⁾ > -] umi-estatria, are new.

The inventive method consists in that in a known manner on the appropriate Steroid with aromatic ring A, which has a hydroxyl group in the 3-position, a compound of the ao general formula

, C ₂ H ₅

x - (ch ₂ ) ₂ —n:

^v C ₂ H ₅

wherein X represents a halogen atom other than fluorine, in a lower alcohol in the presence of a corresponding one Allows alkali metal alcoholate to act, the base isolated as the corresponding halohydrate is optionally converted into the free base and the latter optionally converted into another pharmacologically acceptable salt, in particular nitric acid. An advantageous embodiment of the process according to the invention consists in that one the chlorine derivative is used as the / 9-halogenated amine derivative and the reaction is carried out in a methanolic medium in the presence of sodium methylate.

The following examples illustrate the process of the invention.

The melting points given are the melting points determined on the Kofier bench.

B e i s ρ i e i 1

Production of
3 - (/? - diethylaminoethoxy) -l

45

Analysis: C ₂₄ H »Ο, Ν H 9.55%, N 3.79%; Calculated .. C 78.0%, H 9.3%, N 3.9%. found .. C 78.0%,

Starting from 3 g of 3-hydroxy-16-oxo / l '-'- """' - ostra-irien and 2.2 g / 9-diethylaminoethyl chloride, the hydrochloride of 3 is obtained in a yield of 66.5% - (/? - diethylaiiiinoethoxy) -16-oxo- / l ¹ " ¹ ' ^s ' ¹⁰ ' -estratrien gis white, powdery product with a temperature of 212 ± 5 ° C.

The connection has not yet been made in the literature described.

The free base, in a 49% yield. based on 3-hydroxy-16-oxo- / l ^l ' ³ ' ⁸ ( ^t0 > -estratria, is obtained, melts at 100 ° ± I ⁰ C, (α] 5? = -71.2 " (c = 1 %. Chloroform). It takes the form of colorless prisms that are soluble in acetone, benzene, chloroform, olive oil and ether and insoluble in water.

The compound has not yet been described in the literature.

The compound works when administered buccally at a dose of 0.1 mg per rat for 22 days in rats that were injected with Triton WR 1339 were made artificially hypercholesterolemic, a 12% reduction in cholesterol. At a dose of 1 mg per rat by subcutaneous route, the compound is devoid of estrogenic activity.

Example 2

Production of

3 - (/ 9-DiethyIaminoethoxy) -17-oxo- / J ¹ · ³ · ^{6 '10} ) -lumi-estatriene

Starting from 1 g Lumiöstron uno 1 g / 3 DiäthyI-aminoäthylchlorid obtained the hydrochloride of 3 - (ß - Diäthylaminoäthoxy) - 17 - oxo - J ¹ · ³ · ^{6 '10} "östratrien in aqueous solution, which can directly for the preparation of the free base is used. The compound has not yet been described in the literature.

The free base, in a yield of 36.6%. based on Lumiestrone, melts at 82 ± 2 ° C, [xYS = -270 ° (c - 0.84%, chloroform). It takes the form of colorless needles that are soluble in acetone, benzene, chloroform, olive oil, and ether and insoluble in water.

Analysis: C ₂₄ H ₃₅ O ₂ N = 369.53.

Calculated ... C 78.0%, H 9.55%. N 3.79%;
found ... C 77.9%, H 9.6%, N 3.9%.

The compound has not yet been described in the literature

The compound decreased when administered buccally at a dose of 0.1 mg for 23 days per rat on rats artificially made hypercholesterolemic by injection of Triton WR 1339 were, the cholesterol content by 15% and the lipemia by 10% - In a dose of 1 mg on subcutaneous It is way without estrogenic effects.

Claims (3)

Patent claims: 1. 3 - (ß- diethylaminoethoxy) -Ιό-οχο-Λ ¹ · ³ · ⁵ « ¹⁰ ) -estratriene and its chlorohydrr Λ. 2. 3-fJ? -Diethylaminoethoxy) -Π-οχο-Λ ¹ · ³ · ^{6 '10} ) -lumi-estatriene and its hydrochloride. 3. Process for the preparation of 3 - (/? - diethylaminoethoxy) -16- oxo-A ι- ³ · * (ΐο) -estratrien and 3 - (/? - diethyhminoethoxy) - 17-oxo- /) ¹ ^ ³ C ⁰ ) -lumiöstratriene, in which the angular 13-methyl group is / 9-oriented if the ring D has a keto function in the 16-position, and -oriented if the ring D has a keto function in the 17-position, as well as pharmacologically Compatible salts of these compounds, characterized in that, in a manner known per se, a compound of the general formula is added to the corresponding steroid with aromatic ring A which has a hydroxyl group in the 3-position x- (CH ₉ ), - N: wherein X represents a halogen atom other than fluorine, in a lower alcohol in the presence of a corresponding one Allow alkali metal alcoholate to act. i 668 611 the base isolated as the corresponding halohydrate, if appropriate, into the corresponding free base converted and the latter, if necessary, into another pharmacologically acceptable salt, in particular of nitric acid.