Steroid derivatives

Claim 2

A steroid derivative of the formula:- wherein ST is a 7α-linked steroid nucleus of the general formula:- wherein the dotted lines between carbon atoms 6 and 7, and carbon atoms 8 and 9, of the steroid nucleus indicate that there is an optional double bond between carbon atoms 6 and 7, or that there are two optional double bonds between carbon atoms 6 and 7 and carbon atoms 8 and 9; wherein the aromatic ring A may optionally bear one or two halogen or alkyl substituents; 3 wherein R is hydrogen or alkyl, alkanoyl, alkoxycarbonyl, carboxyalkanoyl or aroyl each of up to 10 carbon atoms; 16 wherein R is hydrogen, alkyl of up to 6 carbon atoms which is preferably in theβ -configuration, or hydroxy which is preferably in theα-configuration; wherein either R 17 (in theβ-configuration) is hydroxy or alkanoyloxy, carboxyalkanoyloxy or aroyloxy each of up to 10 carbon atoms; and R (in the α-configuration) is hydrogen or alkyl, alkenyl or alkynyl each of up to 6 carbon atoms ; or R 17 and R 27 together form oxo (=0); wherein R 18 is alkyl of up to 6 carbon atoms; wherein A is straight- or branched- chain alkylene, alkenylene or alkynylene each of from 3 to 14 carbon atoms, which may have one or more hydrogen atoms replaced by fluorine atoms, or has the formula 1 11 wherein A and A are each alkylene or alkenylene, optionally fluorinated, having together a total of 2 to 13 carbon atoms and Y is -O-, -S-, -SO-, -SO -, -CO-2 or -NR- wherein R is hydrogen or alkyl of up to 3 carbon atoms; 1 or A is alkylene or alkenylene, optionally fluorinated, and A is a direct link or alkylene or alkenylene, optionally fluorinated, such that A 1 and A 11 together have a total of 1 to 12 carbon atoms, and Y is -NRCO-, -CONR-, -COO-, -OCO- or phenylene wherein R has the meaning stated above; wherein R is hydrogen, or alkyl, alkenyl, cycloalkyl, halogenoalkyl, carboxyalkyl, alkoxycarbonylalkyl, aryl or arylalkyl each of up to 10 carbon atoms, or dialkylaminoalkyl wherein each alkyl is of up to 6 carbon atoms, or R is joined to R as defined below; 2 and wherein X is -CONR -, 12 -NR-CO-, -NR 12 CS-, -NR 12 -CONR 2 -, -SO 2 NR 2 - or -CO-; 1 2 or, when R is not hydrogen, is -0 - , -NR -, -(NO)R 2 -, -(PO)R -, -NR 12 -COO-; -NR 12 -SO -, -S-, 2 -SO- or -SO -; 2 2 wherein R is hydrogen or alkyl of up to 6 carbon atoms, or R 1 and R 2 together form alkylene or halogenoalkylene such that, with the adjacent nitrogen atom, they form a heterocyclic ring of 5 to 7 ring atoms, one of which atoms may be a second heterocyclic atom selected from oxygen, sulphur and nitrogen; 12 wherein R is hydrogen or alkyl of up to 6 carbon atoms; 22 and wherein R is hydrogen, cyano or nitro; or a salt thereof when appropriate.

Claim 3

A steroid derivative as claimed in claim 1 which has the formula:- 17 27 wherein R is hydroxy and R is hydrogen or ethynyl, or R 17 and R 27 together form oxo; wherein -A- is -(CH ) -, wherein n is an integer 2 n from 3 to 14, or -A- is:- wherein m is an integer from 2 to 9 and p is 0 to 2; wherein R 1 is alkyl, fluoroalkyl or cycloalkyl each of up to 10 carbon atoms, or phenyl, chlorophenyl or benzyl, or is linked to R 2 as stated below; wherein X is -CONR 2 -, -NR 12 CO-, - S -, -SO- or -SO -, 2 2 wherein R is hydrogen or alkyl of up to 3 carbon atoms or together with R forms alkylene of 5 or 6 carbon atoms, and wherein R 12 is hydrogen or alkyl of up to 3 carbon atoms.

Claim 4

A steroid derivative as claimed in claim 2 wherein the number of carbon 1 atoms in the two groups A and R adds up to between 12 and 16 inclusive.

Claim 5

The compound N-n-butyl-N-methyl-, N-2,2,3,3,4,4,4-heptafluorobutyl-N-methyl- or N, N-(3-methylpentamethylene)-11-(3,17β-dihydroxyoestra-1,3,5(10)-trien-7a-yl)undecamide; N-n-butyl- or N-2,2,3,3,4,4,4- heptafluorobutyl-3-p-[4-(3,17β-dihydroxyoestra-1,3,5(10)-trien-7α-yl)butyl]phenylpropionamide; 7α-(10-p-chlorophenylthiodecyl)-, 7α-(10-p-chlorophenylsulphinyldecyl)-,7α-[9-(4,4,5,5,5-penta- fluorosulphonylnonyl]-, 7α-[10-(4,4,4-trifluorobutyl- sulphinyl)decyl]- or 7α-[10-(p-chlorobenzylsulphinyl)-decyl]oestra-1,3,5(10)-triene- 3,17β-diol; or 7α-(9-n-heptylsulphinylnonyl)oestra-1,3,5(10)-triene-3,17β-diol.

Claim 6

The compound N-n-butyl-N-methyl-, N-2,2,3,3,4,4,4-heptafluorobutyl-N-methyl- or N, N-(3-methylpentamethylene)-11-(3,17β-dihydroxyoestra-1,3,5(10)-trien-7a-yl)undecamide; N-n-butyl- or N-2,2,3,3,4,4,4- heptafluorobutyl-3-p-[4-(3,17β-dihydroxyoestra-1,3,5(10)-trien-7α-yl)butyl]phenylpropionamide; 7α-(10-p-chlorophenylthiodecyl)-, 7α-(10-p-chlorophenylsulphinyldecyl)-,7α-[9-(4,4,5,5,5-penta- fluorosulphonylnonyl]-, 7α-[10-(4,4,4-trifluorobutyl- sulphinyl)decyl]- or 7α-[10-(p-chlorobenzylsulphinyl)-decyl]oestra-1,3,5(10)-triene- 3,17β-diol; or 7α-(9-n-heptylsulphinylnonyl)oestra-1,3,5(10)-triene-3,17β-diol.

Claim 7

A process for the manufacture of a steroid derivative claimed in Claim 1, which comprises: (a) when X has the formula -CONR 2 -, -CSNR 2- or -S0 2 NR 2- , the reaction of a compound of the formula ST 1 -A-Z 1 , wherein A has the meaning stated in claim 1, wherein ST either has the same meaning as stated in claim 1 for ST, or is an equivalent 7α-linked steroid nucleus which bears one or more protecting groups for functional derivatives, and wherein Z 1 is an activated group derived from a carboxylic, thiocarboxylic or sulphonic acid, with an amine of the formula HNR 1 R 2 , wherein wherein 1 2 R and R have the meanings stated in claim 1; or (b) when X has the formula -CO-, the reaction of an acid of the formula ST -A-COOH, wherein ST and A have the meanings stated above, with an organometallic compound of the formula R -M, wherein R has the meaning stated above and M is a metal group; 2 or (c) when X has the formula -S-, -O-, -NR - or (PO)R 2 , the reaction of a compound of the formula ST 1 -A-Z 2 , wherein ST and A have the meanings 2 stated above and wherein Z is a displaceable group, with a compound of the formula R SH, R OH, HNR 1 R 2 or R 1 R 2 P-C 6 H 5 , wherein R and R2 have the meanings stated above, whereafter a phosphonium salt is hydrolysed to the phosphinyl compound; or (d) when X has the formula -NR 12 CO-, -NR 12 CS-, 12 2 -NR CONR -, 12 -NR COO- or 12 -NR SO -, the reaction of a compound of the formula 1 2 12 1 12 ST -A- NHR , wherein ST , A and R have the meanings stated above, with an acylating agent derived from an acid of the formula R COOH, R CSOH, 1 1 R OCOOH or R SO OH; or, for the manufacture of a 2 1 urea, with an isocyanate of the formula R NCO; or, for the manufacture of a guanidine, with a cyanamide of the formula R 1 NR 2 -CN; or (e) when -A- is alkenylene of the formula -A 3 -CH=CH-A 4 -, the reaction of a compound of the formula:- 1 3 wherein ST and A have the meanings stated above, with a triphenylphosphonium salt of the formula:- 1 4 wherein R , X and A have the meanings stated above and wherein Q is an anion; wherafter: (i) any protecting group in ST 1 is removed by conventional means; or (ii) a steroid derivative wherein ST is a 17 -hydroxy-steroid derivative may be converted by conventional reactions into the corresponding 17- keto steroid derivative, and thence to the corresponding 17 -hydroxy-17 -hydrocarbyl steroid derivative (that is,a 27 steroid derivative wherein R is alkyl, alkenyl or alkynyl); 317 or (iii) a steroid derivative wherein R and/or R are other than hydrogen may be obtained from the corresponding compound wherein R and/or R 17 are hydrogen by a conventional etherification or esterification process; or (iv) a steroid derivative wherein R 3 and/or R 17 are hydrogen may be obtained by hydrolysis of the corresponding compound wherein R 3 and/or R 17 are other than hydrogen; or (v) a steroid derivative wherein A is alkenylene may be hydrogenated to provide the corresponding compound wherein A is alkylene; or (vi) a steroid derivative wherein -X- is -CH 2 NR 2 - or -NR CH 2 - may be obtained by the reduction of the corresponding compound wherein -X- is -CONR 2 - or -NR 2 CO-; or (vii) a steroid derivative wherein -X- is -CSNH- or -NHCS- may be obtained by the reaction of the corresponding compound wherein X is -CONH- or -NHCO- with 2,4-bis-(4-methoxyphenyl)-l,3-dithia-2,4- diphosphetane-2,4-disulphide; or (viii) a steroid derivative wherein X is -(NO)R 2 , -SO- or -SO 2 - may be obtained by the oxidation of the corresponding compound wherein X is -NR 2- or - S -.

Claim 8

A pharmaceutical composition comprising a steroid derivative, claimed in claim 1, together with a pharmaceutical acceptable diluent or carrier.

Claim 9

A composition as claimed in claim 6 which contains, in addition to the steroid derivative, one or more antiandrogenic agents or antiprogestational agents.

Claim 10

A composition as claimed in claim 6 which is suitable for oral administration and which contains from 5 to 500 mg. of a steroid derivative.

Claim 11

A method for producing an antioestrogenic effect in a warm-blooded animal in need of such treatment, which comprises administering to said animal an effective amount of at least one steroid derivative as claimed in claim 1.

Claim 12

Claims for Austria

Claim 13

A process for the manufacture of a steroid derivative of the formula:- wherein ST is a 7α-linked steroid nucleus of the general formula:- wherein the dotted lines between carbon atoms 6 and 7, and carbon atoms 8 and 9, of the steroid nucleus indicate that there is an optional double bond between carbon atoms 6 and 7, or that there are two optional double bonds between carbon atoms 6 and 7 and carbon atoms 8 and 9; wherein the aromatic ring A may optionally bear one or two halogen or alkyl substituents; wherein R 3 is hydrogen or alkyl, alkanoyl, alkoxycarbonyl, carboxyalkanoyl or aroyl each of up to 10 carbon atoms; wherein R 16 is hydrogen, alkyl of up to 6 carbon atoms which is preferably in the β-configuration, or hydroxy which is preferably in the α-configuration; wherein either R 17 (in the;r-configuration) is hydroxy or alkanoyloxy, carboxyalkanoyloxy or aroyloxy each of up to 10 carbon atoms; and R (in the α-configuration) is hydrogen or alkyl, alkenyl or alkynyl each of up to 6 carbon atoms ; 17 27 or R and R together form oxo (=0); wherein R 18 is alkyl of up to 6 carbon atoms; wherein A is straight- or branched- chain alkylene, alkenylene or alkynylene each of from 3 to 14 carbon atoms, which may have one or more hydrogen atoms replaced by fluorine atoms, or has the formula 1 11 wherein A and A are each alkylene or alkenylene, optionally fluorinated, having together a total of 2 to 13 carbon atoms and Y is -O-, -S-, -SO-, -SO -, -CO-2 or -NR- wherein R is hydrogen or alkyl of up to 3 carbon atoms; or A is alkylene or alkenylene, optionally 11 fluorinated, and A is a direct link or alkylene or 1 alkenylene, optionally fluorinated, such that A and 11 A together have a total of 1 to 12 carbon atoms, and Y is -NRCO-, -CONR-, -COO-, -OCO- or phenylene wherein R has the meaning stated above; wherein R 1 is hydrogen, or alkyl, alkenyl, cycloalkyl, halogenoalkyl, carboxyalkyl, alkoxycarbonylalkyl, aryl or arylalkyl each of up to 10 carbon atoms, or dialkylaminoalkyl wherein each alkyl is of up to 6 carbon atoms, or R is joined to R as defined below; 2 2 12 and wherein X is -CONR -, -CSNR 22 -, -NR CO-, -NR 12 CS-, -NR 12 CONR 2 -, -SO 2 NR 2 - or -CO-; 1 2 or, when R is not hydrogen, is -O-, -NR -, -(N]O)R 2 -, -(PO)R 2 -, -NR 12 COO - ; -NR 12 SO 2 -, -S- , -SO- or -SO 2 -; wherein R 2 is hydrogen or alkyl of up to 6 carbon atoms, or R 1 and R 2 together form alkylene or halogenoalkylene such that, with the adjacent nitrogen atom, they form a heterocyclic ring of 5 to 7 ring atoms, one of which atoms may be a second heterocyclic atom selected from oxygen, sulphur and nitrogen; wherein R 12 is hydrogen or alkyl of up to 6 carbon atoms; 22 and wherein R is hydrogen, cyano or nitro; or a salt thereof when appropriate, characterised by:- (a) when X has the formula -CONR 2- , -CSNR 2- or -SO 2 NR 2 -, the reaction of a compound of the formula ST 1 -A-Z 1 , wherein A has the meaning stated above, wherein ST 1 either has the same meaning as stated above for ST, or is an equivalent 7α-linked steroid nucleus which bears one or more protecting groups for functional derivatives, and wherein Z 1 is an activated group derived from a carboxylic, thiocarboxylic or sulphonic acid, with an amine of the formula HNR 1 R 2 , wherein 1 2 R and R have the meanings stated above; or (b) when X has the formula -CO-, the reaction of an acid of the formula ST 1 -A-COOH, wherein ST 1 and A have the meanings stated above, with an organometallic compound of the formula R 1 -M, wherein R 1 has the meaning stated above and M is a metal group; 2 or (c) when X has the formula -S-, -O-, -NR - or (PO)R 2 , the reaction of a compound of the formula ST 1 -A-Z 2 , wherein ST and A have the meanings stated above and wherein Z 2 is a displaceable group, 1 1 with a compound of the formula R SH, R OH, HNR 1 R 2 or R 1 R 2 P-C 6 H 5 , wherein R 1 and R 2 have the meanings stated above, whereafter a phosphonium salt is hydrolysed to the phosphinyl compound; 12 12 or (d) when X has the formula -NR CO-, -NR CS-, 12 2 -NR CONR -, 12 -NR COO- or 12 -NR SO the reaction of a compound of the formula 1 2 12 1 12 ST -A- NHR , wherein ST , A and R have the meanings stated above, with an acylating agent derived from an acid of the formula R 1 COOH, R 1 CSOH, 1 1 R OCOOH or R SO OH; or, for the manufacture of a 2 1 urea, with an isocyanate of the formula R NCO; or, for the manufacture of a guanidine, with a cyanamide of the 1 2 formula R NR -CN; or (e) when -A- is alkenylene of the formula -A 3 -CH=CH-A 4 -, the reaction of a compound of the formula:- 1 3 wherein ST and A have the meanings stated above, with a triphenylphosphonium salt of the formula:- 1 4 wherein R , X and A have the meanings stated above and wherein Q is an anion; wherafter: (i) any protecting group in ST 1 is removed by conventional means; or (ii) a steroid derivative wherein ST is a 17 -hydroxy-steroid derivative may be converted by conventional reactions into the corresponding 17- keto steroid derivative, and thence to the corresponding 17 -hydroxy-17 -hydrocarbyl steroid derivative (that is,a steroid derivative wherein R 27 is alkyl, alkenyl or alkynyl); or (iii) a steroid derivative wherein R and/or R are other than hydrogen may be obtained from the corresponding compound wherein R 3 and/or R 17 are hydrogen by a conventional etherification or esterification process; or (iv) a steroid derivative wherein R 3 and/or R 17 are hydrogen may be obtained by hydrolysis of the corresponding compound wherein R 3 and/or R 17 are other than hydrogen; or (v) a steroid derivative wherein A is alkenylene may be hydrogenated to provide the corresponding compound wherein A is alkylene; or (vi) a steroid derivative wherein -X- is -CH 2 NR 2 - or -NR CH 2 - may be obtained by the reduction of the corresponding compound wherein -X- is -CONR 2 - or -NR 2 CO-; or (vii) a steroid derivative wherein -X- is -CSNH- or -NHCS- may be obtained by the reaction of the corresponding compound wherein X is -CONH- or -NHCO- with 2,4-bis-(4-methoxyphenyl)-1,3-dithia-2,4- diphosphetane-2,4-disulphide; or (viii) a steroid derivative wherein X is -(NO)R 2 , -SO- or -SO - may be obtained by the oxidation of the corresponding compound wherein X is -NR 2- or - S -.

Claim 14

A process for the manufacture of a steroid derivative of the formula:- wherein ST is a 7α-linked steroid nucleus of the general formula:- wherein the dotted lines between carbon atoms 6 and 7, and carbon atoms 8 and 9, of the steroid nucleus indicate that there is an optional double bond between carbon atoms 6 and 7, or that there are two optional double bonds between carbon atoms 6 and 7 and carbon atoms 8 and 9; wherein the aromatic ring A may optionally bear one or two halogen or alkyl substituents; wherein R 3 is hydrogen or alkyl, alkanoyl, alkoxycarbonyl, carboxyalkanoyl or aroyl each of up to 10 carbon atoms; wherein R 16 is hydrogen, alkyl of up to 6 carbon atoms which is preferably in the β-configuration, or hydroxy which is preferably in the α-configuration; wherein either R 17 (in the;r-configuration) is hydroxy or alkanoyloxy, carboxyalkanoyloxy or aroyloxy each of up to 10 carbon atoms; and R (in the α-configuration) is hydrogen or alkyl, alkenyl or alkynyl each of up to 6 carbon atoms ; 17 27 or R and R together form oxo (=0); wherein R 18 is alkyl of up to 6 carbon atoms; wherein A is straight- or branched- chain alkylene, alkenylene or alkynylene each of from 3 to 14 carbon atoms, which may have one or more hydrogen atoms replaced by fluorine atoms, or has the formula 1 11 wherein A and A are each alkylene or alkenylene, optionally fluorinated, having together a total of 2 to 13 carbon atoms and Y is -O-, -S-, -SO-, -SO -, -CO-2 or -NR- wherein R is hydrogen or alkyl of up to 3 carbon atoms; or A is alkylene or alkenylene, optionally 11 fluorinated, and A is a direct link or alkylene or 1 alkenylene, optionally fluorinated, such that A and 11 A together have a total of 1 to 12 carbon atoms, and Y is -NRCO-, -CONR-, -COO-, -OCO- or phenylene wherein R has the meaning stated above; wherein R 1 is hydrogen, or alkyl, alkenyl, cycloalkyl, halogenoalkyl, carboxyalkyl, alkoxycarbonylalkyl, aryl or arylalkyl each of up to 10 carbon atoms, or dialkylaminoalkyl wherein each alkyl is of up to 6 carbon atoms, or R is joined to R as defined below; 2 2 12 and wherein X is -CONR -, -CSNR 22 -, -NR CO-, -NR 12 CS-, -NR 12 CONR 2 -, -SO 2 NR 2 - or -CO-; 1 2 or, when R is not hydrogen, is -O-, -NR -, -(N]O)R 2 -, -(PO)R 2 -, -NR 12 COO - ; -NR 12 SO 2 -, -S- , -SO- or -SO 2 -; wherein R 2 is hydrogen or alkyl of up to 6 carbon atoms, or R 1 and R 2 together form alkylene or halogenoalkylene such that, with the adjacent nitrogen atom, they form a heterocyclic ring of 5 to 7 ring atoms, one of which atoms may be a second heterocyclic atom selected from oxygen, sulphur and nitrogen; wherein R 12 is hydrogen or alkyl of up to 6 carbon atoms; 22 and wherein R is hydrogen, cyano or nitro; or a salt thereof when appropriate, characterised by:- (a) when X has the formula -CONR 2- , -CSNR 2- or -SO 2 NR 2 -, the reaction of a compound of the formula ST 1 -A-Z 1 , wherein A has the meaning stated above, wherein ST 1 either has the same meaning as stated above for ST, or is an equivalent 7α-linked steroid nucleus which bears one or more protecting groups for functional derivatives, and wherein Z 1 is an activated group derived from a carboxylic, thiocarboxylic or sulphonic acid, with an amine of the formula HNR 1 R 2 , wherein 1 2 R and R have the meanings stated above; or (b) when X has the formula -CO-, the reaction of an acid of the formula ST 1 -A-COOH, wherein ST 1 and A have the meanings stated above, with an organometallic compound of the formula R 1 -M, wherein R 1 has the meaning stated above and M is a metal group; 2 or (c) when X has the formula -S-, -O-, -NR - or (PO)R 2 , the reaction of a compound of the formula ST 1 -A-Z 2 , wherein ST and A have the meanings stated above and wherein Z 2 is a displaceable group, 1 1 with a compound of the formula R SH, R OH, HNR 1 R 2 or R 1 R 2 P-C 6 H 5 , wherein R 1 and R 2 have the meanings stated above, whereafter a phosphonium salt is hydrolysed to the phosphinyl compound; 12 12 or (d) when X has the formula -NR CO-, -NR CS-, 12 2 -NR CONR -, 12 -NR COO- or 12 -NR SO the reaction of a compound of the formula 1 2 12 1 12 ST -A- NHR , wherein ST , A and R have the meanings stated above, with an acylating agent derived from an acid of the formula R 1 COOH, R 1 CSOH, 1 1 R OCOOH or R SO OH; or, for the manufacture of a 2 1 urea, with an isocyanate of the formula R NCO; or, for the manufacture of a guanidine, with a cyanamide of the 1 2 formula R NR -CN; or (e) when -A- is alkenylene of the formula -A 3 -CH=CH-A 4 -, the reaction of a compound of the formula:- 1 3 wherein ST and A have the meanings stated above, with a triphenylphosphonium salt of the formula:- 1 4 wherein R , X and A have the meanings stated above and wherein Q is an anion; wherafter: (i) any protecting group in ST 1 is removed by conventional means; or (ii) a steroid derivative wherein ST is a 17 -hydroxy-steroid derivative may be converted by conventional reactions into the corresponding 17- keto steroid derivative, and thence to the corresponding 17 -hydroxy-17 -hydrocarbyl steroid derivative (that is,a steroid derivative wherein R 27 is alkyl, alkenyl or alkynyl); or (iii) a steroid derivative wherein R and/or R are other than hydrogen may be obtained from the corresponding compound wherein R 3 and/or R 17 are hydrogen by a conventional etherification or esterification process; or (iv) a steroid derivative wherein R 3 and/or R 17 are hydrogen may be obtained by hydrolysis of the corresponding compound wherein R 3 and/or R 17 are other than hydrogen; or (v) a steroid derivative wherein A is alkenylene may be hydrogenated to provide the corresponding compound wherein A is alkylene; or (vi) a steroid derivative wherein -X- is -CH 2 NR 2 - or -NR CH 2 - may be obtained by the reduction of the corresponding compound wherein -X- is -CONR 2 - or -NR 2 CO-; or (vii) a steroid derivative wherein -X- is -CSNH- or -NHCS- may be obtained by the reaction of the corresponding compound wherein X is -CONH- or -NHCO- with 2,4-bis-(4-methoxyphenyl)-1,3-dithia-2,4- diphosphetane-2,4-disulphide; or (viii) a steroid derivative wherein X is -(NO)R 2 , -SO- or -SO - may be obtained by the oxidation of the corresponding compound wherein X is -NR 2- or - S -.

Claim 15

A process as claimed in claim 1 for the manufacture of a steroid derivative of the formula ST-A-X-R 1 wherein ST has the formula:- 17 27 wherein R is hydroxy and R is hydrogen or ethynyl, or R 17 and R 27 together form oxo; wherein -A- is -(CH ) -, wherein n is an integer 2 n from 3 to 14, or -A- is:- wherein m is an integer from 2 to 9 and p is 0 to 2; wherein R is alkyl, fluoroalkyl or cycloalkyl each of up to 10 carbon atoms, or phenyl, chlorophenyl or benzyl, or is linked to R 2 as stated below; wherein X is -CONR 2 -, -NR 12 CO-, -S-, -SO- or -SO 2 -, wherein R 2 is hydrogen or alkyl of up to 3 carbon atoms or together with R 1 forms alkylene of 5 or 6 carbon atoms, and wherein R 12 is hydrogen or alkyl of up to 3 carbon atoms, characterised by:- (a) when X has the formula -CONR 2 -, the reaction of a compound of the formula ST 1 -A-Z 1 , wherein A has the meaning stated above, wherein ST 1 either has the same meaning as stated above for ST, or is an equivalent 7α-lihked steroid nucleus which bears one or more protecting groups for functional derivatives, and wherein Z 1 is an activated group derived from a carboxylic acid, with an amine of the 12 1 2 formula HNR R , wherein R and R have the meanings stated above; or (b) when X has the formula -S-, the reaction of a compound of the formula ST 1 -A-Z 2 , wherein ST 1 and A have the meanings stated above and wherein Z 2 is a displaceable group, with a compound of the formula R SH, wherein R 1 has the meaning stated above; or (c) when X has the formula -NR 12 CO-, the reaction of a compound of the formula 1 12 1 12 ST -A- NHR , wherein ST , A and R have the meanings stated above, with an acylating agent derived from an acid of the formula R 1 COOH; or (d) when -A- is alkylene of the formula 3 4 -A -CH 2 -CH 2 -A -, the reaction of a compound of the formula:- 1 3 wherein ST and A have the meanings stated above, with a triphenylphosphonium salt of the formula:- 1 4 wherein R , X and A have the meanings stated above and wherein Q is an anion. followed by the hydrogenation of the alkenylene group -A 3 -CH=CH-A 4 - thus formed; whereafter: (i) any protecting group in ST 1 is removed by conventional means; or (ii) a steroid derivative wherein ST is a 17 -hydroxy-steroid derivative may be converted by conventional reactions into the corresponding 17- keto steroid derivative, and thence to the corresponding 17 -hydroxy-17 -ethynyl steroid derivative; or (iii) a steroid derivative wherein X is -SO- or -SO - may be obtained by the oxidation of the corresponding compound wherein X is -S-.