Schering Aktiengesellschaft

Schering, A.g. Patentabteilung

Wolfgang Losert

Rudolf Wiechert

Olaf Loge

Dieter Bittler

Werner Skuballa

Helmut Vorbruggen

Bernd Raduchel

Walter Elger

Henry Laurent

Klaus Nickisch

Ulrich Kerb

Helmut Biere

Jorge Casals-Stenzel

Ekkehard Schillinger

Clemens Rufer

Hanns Ahrens

Ralph Schmiechen

Gerda Mannesmann

Eberhard Schroeder

Klaus Prezewowsky

Jorge Casals

Gerhard Sauer

Bernd Muller

Helmut Hofmeister

Helmut Vorbrueggen

Bernd Raduechel

Klaus Annen

Sybille Beier

David A Henderson

Eberhard Schroder

Peter Esperling

Guenter Neef

Ralph Rohde

Rainer Philippson

Bernhard Krieger

1.alpha.,7.alpha.-dithio-substituted spirolactones, processes for their

Compounds of the formula ##STR1## wherein R.sub.1 is (a) hydrogen, (b) C.sub.1-10 alkyl, (c) C.sub.1-10 alkyl substituted by halogen; C.sub.1-4 alkoxy; C.sub.6-10 aryl; C.sub.6-10 aryl substituted by 1-3 halogen atoms, a phenyl group, 1-3 C.sub.1-4 alkyl groups or a chloromethyl, fluoromethyl, trifluoromethyl, carboxy, hydroxy or C.sub.1-4 alkoxy group; di-C.sub.1-4 -alkylamino; or tri-C.sub.1-4 -alkylammonium, (d) C.sub.4-10 cycloalkyl, (e) C.sub.4-10 cycloalkyl substituted by C.sub.1-4 alkyl, (f) C.sub.6-10 aryl, (g) C.sub.6-10 aryl substituted by 1-3 halogen atoms, a phenyl group 1-3 C.sub.1-4 alkyl groups or a chloromethyl, fluoromethyl, trifluoromethyl, carboxy, hydroxy or C.sub.1-4 alkoxy group, or (h) an aromatic heterocycle of 5 or 6 ring atoms one of which is O, N or S;

Novel prostacyclin derivatives and a process for the preparation thereof

Novel 7.alpha.-substituted 3-oxo-17.alpha.-pregn-4-ene-21,17-carbolactones of the formula ##STR1## wherein ##STR2## is a CC single or CC double bond or the group ##STR3## R.sup.7 is the group SR', R' being a hydrogen atom or a straight-chain or branched alkyl residue of 1-6 carbon atoms optionally substituted by a hydroxy or acyloxy group, the group COOR' or the group COR' wherein R' is an alkyl group of 1-4 carbon atoms and ##STR4## is a CC single bond or the group ##STR5## have antialdosterone activity with reduced endocrinological side effects.

7.alpha.-Substituted 3-oxo-17.alpha.-pregn-4-ene-21,17-carbolactones,

New 15,16-methylene-17.alpha.-pregna-4,6-diene-21-carboxylic acid salts of formula I ##STR1## wherein R.sup.1 and R.sup.2 each alone is hydrogen or together they form an additional CC bond or a methylene group,

15,16 -Methylene-17.alpha.-pregna-4,6-diene-21-carboxylic acid salts,

Compounds of the formula I ##STR1## wherein R.sub.1 is ##STR2## wherein R.sup.I and R.sup.II each independently is alkyl of 1-4 carbon atoms, or R.sup.I and R.sup.II together with the connecting N-atom form a 5- or 6-membered heterocyclic ring whose remaining atoms are all C-atoms, or which also includes and additional N-atom, an additional O or S atom or a combination thereof; ##STR3## wherein R.sup.I and R.sup.II are as defined above; --SR.sup.III, wherein R.sup.III is methyl, ethyl or phenyl; or

11.beta.-aryl estradienes, processes for their production and

7.alpha.-acylthio-1.alpha.,2.alpha.-methylene-3-oxo-17.alpha.-pregn-4-ene-2 1,17-carbolactones of Formula I ##STR1## wherein ##STR2## and R is a lower saturated acyl radical of 2 to 4 carbon atoms, have a stronger antialdosterone effect and lower side effects than spironoloctone.

7.alpha.-Acylthio-1.alpha.,2.alpha.-methylene-

7.alpha.-acylthio-15,16-methylene-3-oxo-17.alpha.-pregna-1,4-diene-21,17-ca rbolactones of the formula ##STR1## wherein the 15,16-methylene group can be in the .alpha.- or .beta.-configuration, and

7.alph

Prostane derivatives of the formula ##STR1## wherein R.sub.1 is (a) hydrogen, (b) C.sub.1-10 alkyl, (c) C.sub.1-10 alkyl substituted by halogen; C.sub.1-4 alkoxy; C.sub.6-10 aryl; C.sub.6-10 aryl substituted by 1-3 halogen atoms, a phenyl group, 1-3 C.sub.1-4 alkyl groups or a chloromethyl, fluoromethyl, trifluoromethyl, carboxy, hydroxy or C.sub.1-4 alkoxy group; di-C.sub.1-4 -alkylamino; or tri-C.sub.1-4 alkylammonium; (d) C.sub.4-10 cycloalkyl, (e) C.sub.4-10 cycloalkyl substituted by C.sub.1-4 alkyl, (f) C.sub.6-10 aryl, (g) C.sub.6-10 aryl substituted by 1-3 halogen atoms, a phenyl group, 1-3 C.sub.1-4 alkyl groups or a chloromethyl, fluoromethyl, trifluoromethyl, carboxy, hydroxy or C.sub.1-4 alkoxy group, or (h) an aromatic heterocycle of 5 or 6 ring atoms one of which is O, N or S;

Certain pyrrole analogs of prostacyclin derivatives

Compounds of the formula ##STR1## wherein the 15,16-methylene group is in the .alpha.- or .beta.-position, and

6.beta.,7.beta.;15,16-Dimethylene-1,4-androstadien-3-ones, their

Stabilized prostacyclins having a wide range of pharmacological activity and long duration of such activity, have the formula ##STR1## wherein R.sub.1 is (a) OR.sub.3, wherein R.sub.3 is hydrogen, alkyl, cycloalkyl, aryl or a heterocyclic residue; or (b) NHR.sub.4 wherein R.sub.4 is an acid residue;

5-Cyano-prostacyclin derivatives

Compounds of the formula I ##STR1## wherein R.sub.2 is hydrogen or an organic acid residue;

17.beta.-Hydroxy-4-androsten-3-ones and process for the preparation

Crystalline prostanoic acid esters

New spirolactones of the formula ##STR1## R is a lower alkyl of up to 5 carbon atoms, and ##STR2##

Spirolactones

4-Androsten-3-ones of the formula ##STR1## wherein R.sub.1 is hydrogen or the acyl radical of an organic or inorganic acid, R.sub.2 is hydrogen, alkyl, or the acyl radical of an organic or inorganic acid, R.sub.3 is methyl or ethyl, R.sub.4 is hydrogen or methyl, ##STR2## and R.sub.5 is lower alkyl, have diuretic activity.

4-Androsten-3-ones and process for the preparation thereof

Prostanoic acid derivatives of the formula ##STR1## wherein R.sub.1 is a hydrogen atom, alkyl of 1-10 carbon atoms, aryl or --CH.sub.2 --U--V wherein U is a direct bond, carbonyl, or carbonyloxy and V is phenyl or substituted phenyl, e.g. substituted by at least one of phenyl, alkoxy of 1-2 carbon atoms or a halogen atom; one of R.sub.2 and R.sub.3 is hydroxy and the other is a hydrogen atom or R.sub.2 and R.sub.3 collectively are an oxygen atom; A is --CH.sub.2 --CH.sub.2 -- or trans--CH.dbd.CH; B is --CH.sub.2 --CH.sub.2 -- or cis--CH.dbd.CH; D and E collectively are a direct bond, or D is alkylene or 1-5 carbon atoms and E is an oxygen or sulfur atom; R.sub.4 is alkyl of 1-10 carbon atoms, alkyl of 1-5 carbon atoms substituted by unsubstituted or substituted aryl, unsubstituted or substituted aryl, or benzodioxol-2-yl-; X--Y is ##STR2## when one of R.sub.2 and R.sub.3 is a hydroxy group and the other is a hydrogen atom or X--Y is ##STR3## or --CH.dbd.CH-- when R.sub.2 and R.sub.3 collectively are an oxygen atom; and when R.sub.1 is a hydrogen atom, the physiologically acceptable salts thereof with bases, have an activity spectrum similar to but stronger and longer lasting activity than the corresponding natural prostaglandins.

15-Ethylenedioxy-prostanoic acid derivatives and esters thereof and

Growing community of inventors

Berlin, Germany

Wolfgang Losert