Hoffmann-la Roche Inc.

Other

Schering Aktiengesellschaft

Andor Furst

Marcel Muller

Rudolf Wiechert

Ulrich Kerb

Leo Alig

Peter Keller

Werner Meier

Ludwig Labler

Klaus Kieslich

Jurg Albert Gutzwiller

Jean-Marie Cassal

Robert C Nickolson

Gunter Neef

Ulrich Eder

Karl Petzoldt

John William Scott

Paul Buchschacher

The invention is concerned with a process for the preparation of 1 hydrogen or hydroxy cholesterol derivatives and intermediates therefor. The compounds of the present invention are useful as intermediates in the preparation of 24,25-dihydroxy and 1.alpha.,24,25-trihydroxycholecalciferol.

Process for the preparation of cholesterol derivatives and novel

The novel D-homosteroids of the formula ##STR1## wherein R.sup.1 represents a --CN, .dbd.NOH or .dbd.CH--NHOH group; R.sup.2 represents oxo or, where R.sup.1 represents a --CN group, R.sup.2 represents oxo or a --OAc group; or R.sup.1 and R.sup.2 together with carbon atoms 2 and 3 of the steroid skeleton represents a [2,3-d]-fused isoxazole ring, a [3,2-c]-fused pyrazole ring, a [3,2-c]-fused N-acylated pyrazole ring or a [2,3-c]-fused furazan ring; Ac represents an acyl group; R.sup.3 and R.sup.4 represent methyl and R.sup.5 and R.sup.6 together represent an additional bond between carbon atoms 5 and 6 of the steroid skeleton; or R.sup.4 and R.sup.5 together represent --O--, R.sup.3 represents hydrogen or methyl, and R.sup.6 represents hydrogen; R.sup.7 represents hydrogen, lower-alkyl or ethynyl; R.sup.8 represents hydroxy or acyloxy; or R.sup.7 and R.sup.8 together represent a spiroether group of the formula ##STR2## or a spirolactone group of the formula ##STR3## the dotted 16,17-bond is an optional additional carbon-carbon bond; and the dotted 2,3-bond is an additional carbon-carbon bond when R.sup.1 and R.sup.2 together with carbon atoms 2 and 3 form the isoxazole or pyrazole ring or when R.sup.2 represents a --OAc group, inhibit the synthesis of progesterone in organisms and can be used for fertility control. The novel D-homosteroids can be manufactured by molecular modifications of other D-homosteroids.

Novel D-homosteroids

The invention is concerned with a process for the preparation of 1 hydrogen or hydroxy cholesterol derivatives and intermediates therefor. The compounds of the present invention are useful as intermediates in the preparation of 24,25-dihydroxy and 1.alpha., 24,25-trihydroxycholecalciferol.

The present disclosure is directed to 5-oxo- or methylene 17.beta.-hydroxy saturated or unsaturated deA-steroids wherein the 17.alpha.-position contains a propionic acid or propanol substituent and derivatives thereof wherein the hydroxy group at the 17-position forms a lactone ring with the carboxy substituent when the substituent at position 21 is carboxy. The deA-steroids and derivatives of the present disclosure are useful as potassium-sparing diuretics or for flushing oedemas.

deA-steroids

The invention is directed to 3-oxo-D-homosteroids and derivatives thereof which are useful as antiantigens.

D-Homosteroids

17.alpha.-hyroxy- and 17a.alpha.-hydroxy-D-homoetiocarboxylic acids of the formula ##STR1## wherein n is 1 or 2,

Process for the preparation of 17.alpha.-hydroxy- and

The present disclosure is directed to a process for the preparation of cholesterol derivatives from corresponding 21-hydroxymethyl steroidal compounds.

Process for the manufacture of cholesterol derivatives

A process for the synthesis of 1.alpha.,3.beta.-dihydroxy-.DELTA..sup.5 -steroids from steroids such as 1.alpha.,2.alpha.-epoxy-cholesta-4,6-dien-3-one, which is reacted with lithium in liquid ammonia in the absence of a proton donator and subsequently reduced by repeated alternative additions of a proton donator, said additions being followed in each case by an equivalent amount of lithium. The final product, a 1.alpha.,3.beta.-dihydorxy-.DELTA..sup.5 -steroid, is useful in the synthesis of derivatives of cholecalciferol.

Process for 1.alpha.,3.beta.-dihydroxy-.DELTA..sup.5 -steroids

D-Homopregnanes of the formula ##STR1## wherein X is hydrogen, Y is hydroxy or X and Y taken together denote an oxygen to carbon bond; R.sup.6 is hydrogen, R.sup.7 is hydrogen, lower alkanoylthio or aroylthio, or R.sup.6 and R.sup.7 taken together denote a carbon to carbon bond and the dotted line in the 1,2-position of the A-ring together with the corresponding solid line denotes a single or double carbon to carbon bond or a pharmaceutically acceptable basic addition salt thereof when Y is hydroxy having diuretic activity are disclosed.

D-Homopregnanes

The present invention is directed to 3-oxo, 6,9-hydro or halo, 11-oxo or (.alpha.--H,.beta.--OH), 17a-alkanoyloxy, 17a.beta.-carboxylate D-homosteroids which are useful as antiinflammatory agents.

The present disclosure is concerned with 9.alpha.-chloro-17-(m-iodobenzyloxy) steroids and a process for their manufacture. The subject compounds are useful as intermediates in the synthesis of pharmacologically-active substances and have themselves been found to exhibit pharmacological activity.

Steroids and process for their manufacture

D-Homopregnanes of the formula ##STR1## wherein the dotted line in the 1,2-position together with the corresponding solid line denotes a single or double carbon-carbon bond; R.sup.6 is hydrogen, fluoro, chloro or methyl; R.sup.9 is hydrogen, fluoro, chloro or bromo; R.sup.11 is hydroxyl, acyloxy, fluoro or chloro; and R.sup.17a is hydroxyl or acyloxy with the proviso that when R.sup.9 is fluoro, chloro or bromo and R.sup.11 is fluoro or chloro, the atomic number of R.sup.11 is less than or equal to that of R.sup.9 ; and with the further proviso that when R.sup.6 is hydrogen, and R.sup.11 and R.sup.17a are hydroxy or when R.sup.6 is fluoro, R.sup.11 and R.sup.17a are hydroxyl and the dotted line in the 1,2-position together with the corresponding solid line denotes a single carbon-carbon bond, R.sup.9 is fluoro, chloro or bromo and processes for the preparation thereof are disclosed.

The present disclosure is concerned with 17a-(m-iodobenzoyloxy) substituted D-homosteroids and a process for their manufacture. The compounds are useful as intermediates and also as hormonal agents, particularly progestational agents.

The present invention relates to pregnane derivatives of the formula ##STR1## wherein R.sup.1 and R.sup.3 are hydroxyl groups or readily cleavable etherified or esterified hydroxyl groups and R.sup.20 is hydroxymethyl or readily cleavable etherified or esterified hydroxy methyl, formyl, carboxyl or carbalkoxy useful as intermediates for the preparation of 1.alpha.-hydroxycholecalciferols. The present invention also relates to processes for the preparation of the pregnane derivatives and the intermediates thereof.

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Basel, Switzerland

Andor Furst