FR290F - New therapeutic applications of 2,3-epithioids. - Google Patents

Description

290

The present invention relates to an improvement to new therapeutic applications of epithio-2,3 steroids forming the subject of the main French patent No. 919 045 filed December 18, 1962 for "New therapeutic applications of epithio-2,3 - steroids ".

The present invention relates more particularly to 2,3-epJthio-5 17 "-lower alkyl-androstan-17 (?> - ol.

Said 2,3-epithio-17o (-lower alkyl- andrcstan-17P> -ol is represented by the following formula:

OH

where R is a lower alkyl radical (for example: methyl, ethyl 1 g propyl) and the broken liger (f) is a generic indication of the α and (3.

The process of the present invention can be illustrated by the following formulas:

OH

290

in which R 'is a cyano or acyl radical (for example: alkanoyl, aroyl, alkoxycarbonyl, alkoxythiocarbonyl), R "is hydrogen or an acyl radical (for example: alkanoyl, aroyl, alkanesuifonyl) and H a la same meaning as above.

^ Thus, the starting steroid substituted at position 2,3 (II or II1) is treated with the basic agent to give the corresponding 2,3 ~ epithiosteroid (i) As basic agent, a weak base such as alumina can be used. and a strong base like potash and soda. Other basic agents such as potassium carbonate and sodium carbonate can also be used. iq The reaction temperature can be decided according to the kind of starting material and basic agent. For the production of the desired 2,3-epithiosteroid (i) with a good yield, it is generally preferred to carry out the reaction in an inert solvent (for example: methanol, ethanol, propanol, benzene, toluene petroleum ether, dimethyl ether of diethylene glycol) under relatively mild conditions, that is, at a temperature not higher than 100 ° C.

The configuration of the epithio group in the 2,3-epithioeteroid (i) thus produced corresponds to that of the sulfur-containing group in the starting steroid (II or III) substituted at positions 2 and J. Specifically 2o the 2, 3-epithiosteroids include ïle Sot, 3k Tepithio-17 <x-methyl-5 (X.-androstan -17 (1-ol, 2oc, - 3 ".- epithio-: r170c-methyl-5P-androstan 17fi-ol" on 2 (i-3 (i-epithio-17e * -methyl-5P-androstan-17p-ol and the like.

The starting steroid (II or IIl) disubstituted in positions 2,3 can be prepared from 2,3-epoxy 3tero "according to a large number of processes. Some of the processes are schematically represented by the scheme of the figure below where only the nucleus A of the skeleton of the steroid is represented, in which R "! is an acyl radical (for example: alkanoyl, aroyl alkanesulfonyl), X is a halogen, and R 'has the same meaning as above.

The following example illustrates a presently preferred embodiment of the present invention.

EXAMPLE

Preparation of 3c - epitfaio-1 7 <x-methyl-5 <x-androstan-17P ~ ol

290

3

CH3SÇ> 20

NCS ....,

In our suspension do not fchar.esul £ nnyloxy-x * -thiocyanato-17a, -methyl-

5oC-androstan-17fi-ol (2.1 g g.) In a mixture of diethylene glycol dimethyl ether (50 ml) and tetrahydro uranium (10 ml), a solution of potassium hydroxide (2.5 g) in water (,; ml) and the solution re su! taj; te is afritJe all night t. h room temperature (about 1? ° c). To the reaction mixture, water was added and the resulting mixture was stirred with dichloromethane. The dichloromethane layer is washed with water, céchée and evaporated to dryness. The residue is chromatographed on alumina (35 g).

The eluates with a mixture of petroleum ether and benzene (1: 2),

1owith benzene and with a mixture of benzene and ether (95: 5j are combined, concentrated and crystallized from acetone solution to give 2w., 5 (X.-epithio-17tX-methyl-5 & -androstan-17 | 3-ol (912 g) as “needles melting between 168 and 169 ° C.

["]} 0 4 5.4 - 2 ° (c = 1.045 in the oroform ehi}. Iii: 0 5} 56 cm 1.

u J D Y V max

11 Analysis calculated for C B. <n0S:

C 74.94; it 10, Oh; g 10.00 Found: r 75.11; H 10.17: 3 9.8o

The starting body of this example, 2 ^ -methanesu fonyloxy-3cv-thioqyanato-17cx-méthy 1-5cx-androstan-1 can be prepared by processing 2cx-bromc-3-2 (pX0-17 (X-tr. ethyl- (x-androctan-17ji-ol Counsell et al: J. Org. Chem. Vol.? 7, parge 216 (1962) with lithium hydride and tri-t-butoxyaluminum, by treating the resulting product with potash in iopopropanol, treating 2 (i, 3p-epoxy-17a-methyl-5o - androstan-17fi-ol with thiocyanic acid in ether and treating I 2 [i-hydroxy-3ix-thiccyanato-17a.-methyl-5c * -androstan-17 (^ - ° l

Claims (16)

290 methanesulfonyl chloride in pyridine. Although the present process has been cited above taking as an example a steroid having a hydroxyl group at the 17 (3-position) it is obvious that the reaction can proceed in the same way when an acylated hydroxyl group exists at the 17-position. 17b. The 2,3-epithiosteroid (i) prepared by the present method shows particular physiological activity, for example 2 <x, 3 <* - epithio-17: x-methyl-50 (-androstan-17jî- Oral administration to rats has not shown potent myotrophic activities and androçeraes with a level of myotropic and anrrogenic activity in ^ o,; - 'rt h -? J- +.' roTci {'} e :: t .-. tpe agent anabo:: -: ue. The present invention is not limited to the exemplary embodiment which has just been described; on the contrary, it is susceptible of variants and modifications which will appear to those skilled in the art. ABSTRACT 11; The present to the main patent issued December 18, 1962 relates to new therapeutic applications of 2,3-epithiosteroids which are useful as substances with myotropic and androgenic activity. This is particularly the case of 2c *., 3 <x-epithio-17 <x-methyl-5 | X-androstan-17 [} - ol. These compounds can therefore be used as anabolic agents. The useful bodies are: a) - a 2,3-epithiosteroid having the following formula: wherein H is lower alkyl and the 17 (1-hydroxyl group may be free or acylated. b) - 2cx, 3ix-epithio-17cx-methyl-5a-anarostan-17 (? i-ol. 290 5 DOCUMENTARY NOTICE ON NEW PRODUCTS Documents likely to affect the novelty of the medicinal product: - 3 French patent (B.3.K.) n ° 6.706 K; - French patent (B.S.M.) n ° 6.247 K. THIS NOTICE WAS DRAWN UP AFTER OBSERVATIONS SUBMITTED BY THE PATENT HOLDER.