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US 4,386,085 AGranted
Novel steroids
AssigneeRoussell Uclaf
InventorsJean G. Teutsch, Germain Costerousse, Daniel Philibert, Roger Deraedt
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AssigneeRoussell Uclaf
InventorsJean G. Teutsch, Germain Costerousse, Daniel Philibert, Roger Deraedt
Estimating the term…
Novel 19-nor steroids and 19-nor-D-homo-steroids of the formula ##STR1## wherein R.sub.1 is an organic radical of 1 to 18 carbon atoms containing at least one atom selected from the group consisting of nitrogen, phosphorous and silicon with the atom immediately adjacent to the 11-carbon atom being carbon, R.sub.2 is a hydrocarbon of 1 to 8 carbon atoms, X is selected from the group consisting of a pentagonal ring and a hexagonal ring optionally substituted and optionally containing a double bond, B and C together form a double bond or an epoxy group, the C.dbd.A group at position 3 is selected from the group consisting of C.dbd.O, ketal, ##STR2## --C.dbd.NOH, --C.dbd.NOAlK.sub.3 and .dbd.CH.sub.2, AlK.sub.1, AlK.sub.2 and AlK.sub.3 are selected from the group consisting of alkyl of 1 to 8 carbon atoms and aralkyl of 7 to 15 carbon atoms and their non-toxic, pharmaceutically acceptable acid addition salts having anti-glucocorticoid activity and a process for their preparation.
A compound selected form the group consisting of 19-nor steroids and 19-nor-D-homo-steroids of the formula ##STR99## wherein R.sub.1 is an organic radical of 1 to 18 carbon atoms containing at least one atom selected from the group consisting of nitrogen, phosphorous and silicon with the atom immediately adjacent to the 11-carbon atom being carbon, R.sub.2 is a hydrocarbon of 1 to 8 carbon atoms, X is selected from the group consisting of a pentagonal ring and a hexagonal ring optionally substituted and optionally containing a double bond, B and C together form a double bond or an epoxy group, the C.dbd.A group at position 3 is selected from the group consisting of C.dbd.O, ketal, ##STR100## --C.dbd.NOH, --C.dbd.NOAlK.sub.3 and .dbd.CH.sub.2, AlK.sub.1, AlK.sub.2 and AlK.sub.3 are selected from the group consisting of alkyl of 1 to 8 carbon atoms and aralkyl of 7 to 15 carbon atoms and their non-toxic, pharmaceutically acceptable acid addition salts.
A process of claim 16 wherein X and the carbons to which it is attached form the ring of the formula ##STR114## wherein R.sub.2 has the above definition, the dotted line in the 16,17-position is an optional double bond, Y is the group ##STR115## n is 1 or 2, R.sub.5 is selected from the group consisting of hydrogen, alkyl of 1 to 8 carbon atoms, alkenyl and alkynyl of 2 to 8 carbon atoms, aryl of 6 to 14 carbon atoms and aralkyl of 7 to 15 carbon atoms, R.sub.6 may be the same as R.sub.5 and may be selected from the same group of members as R.sub.5 or --OH, R.sub.3 and R.sub.4 are individually selected from the group consisting of hydrogen, --OH, --OAlK.sub.4, --OCOAlK.sub.5, alkenyl and alkynyl of 2 to 8 carbon atoms, ##STR116## and --CN wherein AlK.sub.4, AlK.sub.5 and AlK.sub.8 are selected from the group consisting of alkyl of 1 to 8 carbon atoms and aralkyl of 7 to 15 carbon atoms, AlK.sub.6 is selected from the group consisting of optionally substituted alkyl of 1 to 8 carbon atoms and aralkyl of 7 to 15 carbon atoms and AlK.sub.7 is alkyl of 1 to 8 carbons atoms and R.sub.3 and R.sub.4 form the group ##STR117## and Z.sub.1 is selected from the group consisting of hydrogen, alkyl of 1 to 8 carbon atoms and acyl of an organic carboxylic acid of 1 to 8 carbon atoms and Z.sub.2 is alkyl of 1 to 8 carbon atoms.
A process for the preparation of a compound of the formula ##STR120## wherein R.sub.1, R.sub.2 and K have the above definitions, R.sub.3 ' is selected from the group consisting of --OH and OR.sub.c, R.sub.c is the residue AlK.sub.4 of an ether group or COAlK.sub.5 of an ester group, AlK.sub.4 and AlK.sub.5 having the above definitions, and R.sub.4 ' is hydrogen or alkenyl or alkynyl of 2 to 8 carbon atoms comprising reacting a compound of the formula ##STR121## with a compound selected from the group consisting of LiCu(R.sub.1).sub.2, R.sub.1 Li and R.sub.1 Mg Hal wherein R.sub.1 and Hal have the above definitions in the presence of a cuprous halide to obtain a compound of the formula ##STR122## and either reducing the latter to obtain the corresponding 17-ol compound or with an appropriate magnesium to obtain the corresponding 17.alpha.-substituted-17.beta.-ol steroid or with an organometallic derivative such as a lithium or potassium derivative to obtain the corresponding 17.alpha.-substituted-17.beta.-ol steroid or with a cyanuration agent to obtain the corresponding 17.alpha.-ol-17.beta.-cyano steroid, protecting the hydroxy group and reacting the latter with an organometallic compound as discussed above to obtain the corresponding 17.alpha.-substituted-17.beta.-ol steroid and in the case of one of the compounds obtained is 17-hydroxylated, reacting it with an etherification agent or esterification agent and in the case when one of the compounds contains a 17 substituent with a triple bond reacting the latter with a reducing agent to obtain the corresponding ethylenic derivative.
Dependencies are inferred from the claim text.