Ciba-geigy Corporation

Peter Wieland

Georg Anner

Michel Biollaz

Hellmut Ueberwasser

Novel halogenated steroids of the formula ##STR1## in which X represents a halogen atom having a maximum atomic number of 17,

Halogenated steroids

Novel 19-oxygenated steroids of the 20-spiroxane series of the formula ##STR1## in which R.sup.3 is a lower alkyl radical carrying an oxygen-containing functional group and R.sup.4 is two hydrogen atoms or an oxo group, and which carry a double bond or a methylene group in the 6,7-position or carry a lower alkanoylthio group in the 7.alpha.-position, and the corresponding 17.beta.-hydroxy-21-carboxylic acids of the formula ##STR2## in which R.sup.3 is as defined above, and which carry a double bond or a methylene group in the 6,7-position, as well as salts thereof and 1,2-dehydro derivatives of all of these compounds are advantageous as potassium-saving diuretics in therapy since they antagonize the physiological effects of aldosterone but have only slight side effects on sexual functions of the body. The compounds are obtainable by conventional general preparation processes of steroid chemistry.

Novel steroid compounds having an oxygen function in the 19-position

The invention provides a novel general process for the manufacture of 6.beta.,7-methylene-3-oxo-4-ene-steroids by successively (a) reacting a 3.xi.,5.beta.-dihydroxy-6-ene-steroid which is optionally etherified or esterified in the 3-position with a zinc/copper-methylene iodide reagent to introduce the 6.beta.,7-methylene bridge, (b) liberating an etherified or esterified 3-hydroxyl group if such a group is present, (c) treating the resultant 6.beta.,7-methylene-3.xi.,5.beta.-dihydroxy-steroid with an oxidizing agent to dehydrogenate the 3-hydroxyl group to the oxo group, and (d) dehydrating the 6.beta.,7-methylene-5.beta.-hydroxy-3-oxo-steroid to form the 4,5-double bond. The starting materials, which form a novel class of compounds, can be obtained by a novel process by converting a 5.beta.,6-oxido-3.xi.-hydroxy-steroid with a selenol, for example phenylselenol, to a 6.alpha.-alkyl- or arylseleno-3.xi.,5.beta.-dihydroxy-steroid, oxidizing this compound with a peroxidic reagent, for example hydrogen peroxide, in a weakly acid medium to give the corresponding 6-selenonyl compound, and converting this compound, preferably by treatment with a base, preferably with 1,5-diazabicyclo[4,3,0]non-5-ene, to give the 3.xi.,5.beta.-dihydroxy-6-ene-steroid. During the course of these reactions, the 3-hydroxyl group is preferably temporarily protected by esterification or etherification.

Process for the manufacture of 6.beta.,7-methylene-3-oxo-4-ene steroids

21-Fluoro-19-norpregnadienes of the formula ##STR1## wherein X represents hydrogen, lower alkyl, chlorine or fluorine and R.sub.1 and R.sub.2 each individually denote a hydrogen atom or an acyclic or carbocyclic hydrocarbon radical or both together with the adjacent carbon atom form a cycloaliphatic ring, are useful gestagenic and ovulation-inhibiting agents suitable for oral administration.

Growing community of inventors

Oberwil, Switzerland

Peter Wieland