Ciba-geigy Corporation

Georg Anner

Hansuli Wehrli

Peter Wieland

Charles Meystre

Jaroslav Kalvoda

Michel Biollaz

Adrian Marxer

Hellmut Ueberwasser

Novel 6.alpha.,9.alpha.,21-trihalogeno-11.beta.-hydroxy-16.alpha. or 16.beta.-methyl-17.alpha.-propionyloxy-pregn-4-ene-3,20-dione compounds of the formula ##STR1## in which X represents chlorine or flourine, R represents the group --CH.sub.2 CH--, --CH.dbd.CH-- or --CH.dbd.CCl--, the chlorine atom being in the positon 2 of the steroid numbering, and in which the 16-methyl radical is .alpha.- or .beta.-oriented, are useful pharmaceuticals, especially anti-inflammatory agents for topical administration.

Polyhalogeno-steroids

An advantageous method for the manufacture of steroidal lactones of the spironolactone and canrenone type involves the following reaction sequence: bromination of a 3.beta. ,17-dihydroxy-17.alpha. -pregn-5-en-21-carboxaldehyde in basic or neutral medium, oxidation of the 5,6-dibromo compound with hexavalent chromium compounds under basic or neutral conditions, dehydrobromination with inorganic basic agents, such as lithium halides in the presence of lithium carbonate, or with organic bases, such as pyridine, oxidation of the steroid-4,6-diene compound so obtained having in the 17-position the same substituents as the starting material mentioned, with compounds of hexavalent chromium in acid solution, optionally after pretreatment with an acid or, in particular, with a thiocarboxylic acid (to introduce the 7.alpha.-acylthio group, e.g. if spironolactone is to be manufactured). The new process gives better yields than those hitherto described.

Process for the manufacture of steroid carboxylic acid lactones

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 derivatives of 1-dehydro-6.alpha.,9.alpha.-difluoro-16.alpha.-methyl-corticosterone having an aldehyde group in 21-position instead of the hydroxyl group, and derivatives of such aldehydes having a 2-chlorine atom, the corresponding hydrates, as well as their functional aldehyde derivatives, such as the acetals, display an antiinflammatory and thymolytic action. They are prepared by conventional methods.

Aldehydes of the pregnane series and derivatives thereof

Compounds of the general formula ##STR1## wherein R.sub.1 represents a hydrogen atom or a lower alkyl group, which contain a double bond in 5-position and a methyl group in 10-position, or three double bonds in the position 1,3 and 5)10), and which can contain an additional double bond in the 9(11)-position, are manufactured by a novel process, in which a 17-oxosteroid of the general formula ##STR2## wherein R.sub.1 ' represents a hydrogen atom, a lower alkyl group or an acyl group, and which contains double bonds and optionally a methyl group in the positions indicated above, is reacted with an organometallic compound of the formula

Process for the manufacture of spiro compounds of the steroid series

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

Basel, Switzerland

Georg Anner