# US 5,708,001 A · Substituted 6-azaandrostenones

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- Number: US 5,708,001 A
- Document ID: US5708001A
- Status: Granted
- Kind: A
- Application number: 08/454,166
- Filed: 1995-06-07
- Granted: 1998-01-13
- Earliest claimed: 1995-06-07
- Assignees: Glaxo Wellcome Inc.
- Inventors: Robert Carl Andrews; Cynthia Markert Cribbs; Stephen Vernon Frye; Curt Dale Haffner; Patrick Reed Maloney
- Web page: https://patentgrep.com/patent/US5708001A

## CPC

- C07J 73/005: {by nitrogen as hetero atom}
- C07J: STEROIDS (seco-steroids C07C)

## Abstract

The present invention relates to certain substituted 17.beta.-substituted carbonyl-6-azaandrost-4-en-3-ones of formula (I), wherein R.sup.1 and R.sup.2 i) are independently hydrogen or lower alkyl and the bond between the carbons bearing R.sup.1 and R.sup.2 is a single or a double bond, or ii) taken together are a --CH.sub.2 -- group forming a cyclopropane ring, and the bond between the carbons bearing R.sup.1 and R.sup.2 is a single bond; R.sup.3 is preferably hydrogen, halogen or lower alkyl, R.sup.4 is preferably hydrogen or lower alkyl, X is preferably CH.sub.2, Y is preferably hydrogen and Z is preferably CONR.sup.14 R.sup.15 and R.sup.14 and R.sup.15 are a variety of organic groups, and pharmaceutically acceptable salts thereof, preparation, medical use and pharmaceutical formulations.

## Claims

### Claim 1

A compound of formula (I): ##STR20## wherein R.sup.1 and R.sup.2
i) are independently hydrogen or lower alkyl and the bond between the carbons bearing R.sup.1 and R.sup.2 is a single or a double bond, or
ii) taken together are a --CH.sub.2 -- group forming a cyclopropane ring, and the bond between the carbons bearing R.sup.1 and R.sup.2 is a single bond;
R.sup.3 is hydrogen, --Alk.sup.1 --H (optionally substituted with one or more halogens), lower cycloalkyl, lower cycloalkyl-lower alkyl), halogen, --(Alk.sup.1).sub.n --CO.sub.2 H, --(Alk.sup.1).sub.n --CO.sub.2 R.sup.7, --(Alk.sup.1).sub.n --Ar.sup.1, --(Alk.sup.1).sub.n --CONR.sup.8 R.sup.9, --(Alk.sup.1).sub.n --NR.sup.8 R.sup.9, --(Alk.sup.1).sub.n --S(O).sub.r R.sup.7, --(Alk.sup.1).sub.n --CN, --(Alk.sup.1)--OH, --(Alk.sup.1).sub.n --COR.sup.7 ; or --(Alk.sup.1).sub.n --OR.sup.7 ; wherein
Alk.sup.1 is lower alkylene, lower alkenylene or lower alkynylene,
n is 0 or 1,
r is 0, 1or 2,
R.sup.7 is --Alk.sup.1 --H, --(Alk.sup.1).sub.n --Ar.sup.1 or lower cycloalkyl,
R.sup.8 and R.sup.9 are independently hydrogen, --Alk.sup.1 --H or lower cycloalkyl,
Ar.sup.1 is a homocyclic aryl group of 6 to 14 carbons;
R.sup.4 is hydrogen, --Alk.sup.1 --H, lower cycloalkyl, lower cycloalkyl-lower alkyl, --(Alk.sup.1).sub.n --S(O).sub.r R.sup.7, --(Alk.sup.1).sub.n -phthalimidyl, --(Alk.sup.1)--CO.sub.2 H, --(Alk.sup.1).sub.n --CO.sub.2 R.sup.7, --(Alk.sup.1).sub.n --COR.sup.7, --(Alk.sup.1).sub.n --Ar.sup.1, --(Alk.sup.1).sub.n -CONR.sup.8 R.sup.9, --(Alk.sup.1).sub.n --NR.sup.8 R.sup.9, --(Alk.sup.1).sub.n --OH or --(Alk.sup.1).sub.n --OR.sup.7 ;
X is, ##STR21## wherein R.sup.10, R.sup.11, R.sup.12 and R.sup.13 are independently hydrogen or lower alkyl, p and q are independently either 0or 1; and,
i) Y is hydrogen or hydroxy and
Z is --(Alk.sup.2).sub.n --COR.sup.5, --(Alk.sup.2).sub.n --CO.sub.2 R.sup.5, --(Alk.sup.2).sub.n --COSR.sup.5, --(Alk.sup.2).sub.n --CONR.sup.14 R.sub.15, --(Alk.sup.2)--OCO.sub.2 R.sup.5, --(Alk.sup.2)--OCOR.sup.5, --(Alk.sup.2)--OCONR.sup.14 R.sup.15, --(Alk.sup.2)--OR.sup.5, --(Alk.sup.2)--NR.sup.5 'COR.sup.5, --(Alk.sup.2)--NR.sup.5 'CO.sub.2 R.sup.5, --(Alk.sup.2)--NR.sup.5 CONR.sup.14 R.sup.15, --(Alk.sup.2).sub.n --CONR.sup.5 NR.sup.14 R.sup.15, --(Alk.sup.2).sub.n --CONR.sup.5 CONR.sup.14 R.sup.15, --(Alk.sup.2) --NR.sup.5 CSNR.sup.14 R.sup.15 or --(Alk.sup.2).sub.n --CONR.sup.5 CSNR.sup.14 R.sup.15 ; wherein
Alk.sup.2 is (C.sub.1-12) alkylene, (C.sub.2-12) alkenylene or (C.sub.2-12) alkynylene, R.sup.5 and R.sup.5 ' are independently hydrogen, --Alk.sup.1 --H (optionally substituted independently with one or more CO.sub.2 H, CO.sub.2 R.sup.7, Ar.sup.2, Ar.sup.3 or cyano groups), (Alk.sup.1).sub.n -(lower cycloalkyl (optionally substituted independently with one or more --Alk.sup.1 --H groups)), adamantyl, norbornyl, Ar.sup.2, Ar.sup.3, (lower cycloalkyl)-Ar.sup.2 or (lower cycloalkyl)-Ar.sup.3 ; wherein
Ar.sup.2 is a homocyclic aromatic group of 6 to 14 carbon ring atoms (optionally substituted independently with one or more --Alk.sup.2 -H (optionally substituted independently with one or more halogens), --(Alk.sup.1).sub.n COR.sup.7, --(Alk.sup.1).sub.n --OH, --(Alk.sup.1).sub.n --OR.sup.16,--(Alk.sup.1).sub.n --Ar.sup.3, --(Alk.sup.1).sub.n --CO.sub.2 H, --(Alk.sup.1).sub.n --CO.sub.2 R.sup.7, S(O).sub.r R.sup.7, NR.sup.8 S(O).sub.r R.sup.16, NR.sup.8 R.sup.9, CONR.sup.8 R.sup.9, lower cycloalkyl, lower alkoxy, --(Alk.sup.1).sub.n --Ar.sup.1 (optionally substituted with one or more --Alk.sup.1 --H or halogen), methylenedioxy, ethylenedioxy, morpholino, thiomorpholino, cyano, nitro or halogens); wherein
R.sup.16 is --Alk.sup.1 --H (optionally substituted independently with one or more halogens), lower cycloalkyl (optionally substituted independently with one or more halogens, or --Alk.sup.1 --H (optionally substituted independently with one or more halogens)) or --(Alk.sup.1).sub.n --Ar.sup.1 (wherein Ar.sup.1 is optionally substituted independently with one or more lower alkoxy, cyano, halogen or --Alk.sup.1 --H (optionally substituted independently with one or more halogens);
Ar.sup.3 is an aromatic group of 5 to 14 ring atoms, at least one of which is O, N or S (optionally substituted independently with one or more --Alk.sup.1 --H (optionally substituted independently with one or more halogens), lower cycloalkyl, lower alkoxy, CO.sub.2 H, CO.sub.2 R.sup.7, --(Alk.sup.1).sub.n --Ar.sup.1, cyano or halogen);
R.sup.14 and R.sup.15 are
a) independently, hydroxy, hydrogen, --Alk.sup.2 -H, lower alkoxy, --(Alk.sup.1).sub.n -adamantyl, --(Alk.sup.1).sub.n -myrantyl, --(Alk.sup.1).sub.n -norbornyl, --(Alk.sup.1).sub.n -fluorenyl, --(Alk.sup.1).sub.n -fluorenonyl, --(Alk.sup.1).sub.n -indanyl (optionally substituted with one or more --Alk.sup.1 -H), --Alk.sup.1 --H (optionally substituted independently with one or more halogens, cyano, cycloalkyl, SR.sup.5, COR.sup.5, CONR.sup.5 R.sup.7, NR.sup.5 'COR.sup.5, NR.sup.5 'CO.sub.2 R.sup.5, NR.sup.5 'CONHR.sup.5, CO.sub.2 R.sup.5, OR.sup.5, Ar.sup.2 or Ar.sup.3), Ar.sup.2 or Ar.sup.3 or a saturated C.sub.4-18 bicyclic ring or C.sub.3-11 saturated ring, optionally containing an oxygen or sulfur atom (said rings optionally substituted independently with one or more cyano, R.sup.16, Ar.sup.2 or Ar.sup.3);
b) alkylene groups (optionally substituted with one or more R.sup.7 groups, taken together with the linking nitrogen to form a 4 to 8 atom heterocyclic group) ##STR22## wherein; Het represents --O--, --CH.sub.2 --, --S(O).sub.r --,--(NH)--or --(N(Alk.sup.1 --H))--;
with the proviso that
when Z is --(Alk.sup.2).sub.n --COR.sup.5, --(Alk.sup.2).sub.n --CO.sub.2 R.sup.5 or --(Alk.sup.2).sub.n -CO-thiopyridyl and R.sup.5 is hydrogen, --Alk.sup.1 --H, lower cycloalkyl, or adamantyl or when Z is --(Alk.sup.2).sub.n --CONR.sup.14 R.sup.15 and R.sup.14 and R.sup.15 are
a) independently hydrogen, --Alk.sup.2 -H, lower cycloalkyl, lower alkoxy, adamantyl, --Ar.sup.1, benzyl, diphenylmethyl, triphenylmethyl or --(Alk.sup.1).sub.n -norbornyl; or
b) carbon atoms, optionally substituted with one or more lower alkyl groups, taken together with the linking nitrogen to form a 4 to 8 atom heterocylic ring as herein before defined,
Y is hydroxy; or
ii) Y is hydrogen and
Z is OR.sup.5, OCOR.sup.5, OCONR.sup.14 R.sup.15, NR.sup.5 'COR.sup.5, NR.sup.5 'CO.sub.2 R.sup.5, NR.sup.5 CONR.sup.14 R.sup.15 or NR.sup.5 CSR.sup.14 R.sup.15 ; and
iii) Y and Z taken together are .dbd.O, .dbd.CH--(Alk.sup.1).sub.n --COR.sup.5, .dbd.CH--(Alk.sup.1).sub.n --CO.sub.2 R.sup.5 or .dbd.CH--(Alk.sup.1).sub.n --CONR.sup.14 R.sup.15 ;
R.sup.6 is hydrogen or methyl;
or a pharmaceutically acceptable salt or solvate thereof.

### Claim 2 (depends on 1)

A compound of claim 1 which is a compound of formula (IA), (IB), (IC) or (ID) ##STR23##

### Claim 3 (depends on 1)

A compound as claimed in claim 1 wherein R.sup.3 is hydrogen, halogen, lower alkyl, lower cycloalkyl or lower cycloalkyl-lower alkyl.

### Claim 4 (depends on 3)

A compound as claimed in claim 3 wherein R.sup.3 is hydrogen, halogen or tower alkyl.

### Claim 5 (depends on 1)

A compound of claim 1 wherein R.sup.3 is methyl, ethyl, cyano, iodo, bromo, chloro or dimethylaminomethyl.

### Claim 6 (depends on 1)

A compound as claimed in claim 1 wherein R.sup.4 is hydrogen, lower alkyl, lower cycloalkyl or lower cycloalkyl-lower alkyl.

### Claim 7 (depends on 6)

A compound as claimed in claim 6 wherein R.sup.4 is hydrogen or lower alkyl.

### Claim 8 (depends on 1)

A compound as claimed in claim 1 wherein R.sup.4 is methyl, ethyl, propyl, i-propyl, butyl, i-butylhexyl, 3-hydroxypropyl, propenyl, methylene-cyclopropyl, benzyl, 2-methoxyethyl, 2-acetic acid, 3-proponic acid, 5-pentanoic acid, 6-hexanoic acid, methyl-5-pentanoate, ethyl-6-hexanoate, 3-phthalimidylpropyl and 4-phthalimidylpropyl.

### Claim 9 (depends on 1)

A compound according to claim 1 wherein X is --CH.sub.2 --.

### Claim 10 (depends on 1)

A compound as claimed in claim 1 wherein Y is hydrogen and Z is --(Alk.sup.2).sub.n --COR.sup.5, --(Alk.sup.2).sub.n --CONR.sup.14 R.sup.15, --(Alk.sup.2)--OCO.sub.2 R.sup.5, --(Alk.sup.2)--OCOR.sup.5, --(Alk.sup.2)--NR.sup.5 'COR.sup.5, --(Alk.sup.2).sub.n --CONR.sup.5 NR.sup.14 R.sup.15, --(Alk.sup.2)--NR.sup.5 CONR.sup.14 R.sup.15, or --(Alk.sup.2).sub.n --CONR.sup.5 CONR.sup.14 R.sup.15.

### Claim 11 (depends on 10)

A compound as claimed in claim 10 wherein Z is --COR.sup.5, --CONR.sup.14 R.sup.15, --CH.sub.2 OCO.sub.2 R.sup.5, --CH.sub.2 OCOR.sup.5, --CH.sub.2 NR.sup.5 'COR.sup.5, --CONR.sup.5 NR.sup.14 R.sup.15, --CH.sub.2 NR.sup.5 CONR.sup.14 R.sup.15 or --CONR.sup.5 CONR.sup.14 R.sup.15.

### Claim 12 (depends on 11)

A compound as claimed in claim 11 wherein Z is --CONR.sup.14 R.sup.15.

### Claim 13 (depends on 1)

A compound as claimed in claim 1 wherein Ar.sup.1 is a phenyl group.

### Claim 14 (depends on 1)

A compound as claimed in claim 1 wherein Ar.sup.2 is a phenyl group optionally substituted independently with one or more --Alk.sup.2 -H (optionally substituted independently with one or more halogens), --OR.sup.16, --S(O).sub.r R.sup.7, Ar.sup.1, methylenedioxy, ethylenedioxy, morpholino, thiomorpholino, cyano, nitro or halogen groups.

### Claim 15 (depends on 1)

A compound as claimed in claim 1 wherein R.sup.14 is hydrogen or hydroxy, and R.sup.15 is hydrogen, lower cycloalkyl (optionally substituted independently with one or more R.sup.7 or Ar.sup.2 groups), --(Alk.sup.1)-adamantyl, --(Alk.sup.1).sub.n -myrantyl, --(Alk.sup.1).sub.n -norbornyl, --(Alk.sup.1).sub.n -fluorenyl, --(Alk.sup.1).sub.n -indanyl, --Alk.sup.1 --H (optionally substituted independently with one or more lower cycloalkyl, SR.sup.5, OR.sup.5, Ar.sup.2 or Ar.sup.3 groups), Ar.sup.2 or Ar.sup.3 ; or
R.sup.14 and R.sup.15 are carbon atoms, optionally substituted with one or more R.sup.7 groups, taken together with the linking nitrogen to form a 5 to 7 atom heterocyclic group ##STR24## wherein Het represents --CH.sub.2 --.

### Claim 16 (depends on 1)

A compound as claimed in claim 1 wherein Ar.sup.3 is an aromatic group of five or six ring atoms, at least one of which is O, N or S, optionally substituted independently with one or more Alk.sup.1 H groups.

### Claim 17 (depends on 16)

A compound as claimed in claim 16 wherein Ar.sup.3 is an optionally substituted pyrrolyl, thienyl, furyl or pyridyl group.

### Claim 18 (depends on 1)

A compound as claimed in claim 1 wherein R.sup.5 is hydrogen, lower alkyl optionally substituted independently with one or more Ar.sup.2 groups, (lower alkyl).sub.n -lower cycloalkyl, menthyl, adamantyl, norbornyl or Ar.sup.2.

### Claim 19 (depends on 1)

A compound as claimed in claim 1 wherein Z is --COR.sup.5.

### Claim 20

A compound which is:
17.beta.-(1-Oxo-2-cyclohexylethyl)-6-azaandrost-4-en-3-one;
17.beta.-(1-Oxo-1-(2,4-difluorophenyl)methyl)-6-azaandrost-4-en-3-one;
17.beta.-(1-Oxo-1-(4-isopropoxyphenyl)methyl)-6-azaandrost-4-en-3-one;
1.beta. -(1-Oxo-3,3-diphenylpropyl)-6-azaandrost-4-en-3-one; or
17.beta.-(1-Oxo-1-(2-norbornyl)methyl)-6-azaandrost-4-en-3-one or
a pharmaceutically acceptable salt or solvate thereof.

### Claim 21 (depends on 1)

A compound as claimed in claim 1 wherein Z is --CONR.sup.14 R.sup.15, R.sup.14 is hydrogen and R.sup.15 is Ar.sup.2 or a C.sub.3-11 saturated ring, optionally containing an oxygen or sulphur atom (optionally substituted independently with one or more R.sup.7 or Ar.sup.2 groups).

### Claim 22 (depends on 1)

A compound as claimed in claim 1 wherein R.sup.15 is a group of formula Ar.sup.2a ##STR25## wherein R.sup.a and R.sup.b are independently hydrogen, lower alkyl, trifluoromethyl, halogen or phenyl (optionally substituted with one or more halogens or branched C.sub.4-7 alkyl) and R.sup.c is hydrogen or one or more halogens, or R.sup.15 is a C.sub.3-11 saturated ring, optionally containing an oxygen or sulphur atom substituted with a group of formula Ar.sup.2a.

### Claim 23 (depends on 1)

A compound as claimed in claim 1 wherein R.sup.15 is a group of formula Ar.sup.2aa ##STR26## where R.sup.aa is branched C.sub.4-7 alkyl, trifluoromethyl or phenyl optionally substituted with one or more halogens; one of R.sup.ba and R.sup.ca is branched C.sub.4-7 alkyl, trifluoromethyl, halogen or phenyl optionally substituted with one or more halogens, and the other is hydrogen or halogen; and R.sup.da is hydrogen or halogen.

### Claim 24 (depends on 1)

A compound as claimed in claim 1 which is:
17.beta.-N-((2,6-Di-i-propyl)phenyl)-carbamoyl-6-azaandrost-4-en-3-one
1.beta. -N-(2,4,6-trimethyl)phenyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-(2-Chloro-5-trifluoromethyl)phenyl-carbamoyl-6-azaandrost-4-en-3 -one
17.beta.-N-(2,6-Dimethyl-4-bromo)phenyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-(2,6-Dimethyl-4-t-butyl)phenyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-(2,6-Dibromo-4-isopropyl)phenyl-carbamoyl-6-azaandrost-4-en-3-on
17.beta.-N-(2,5-Ditrifluoromethyl)phenyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-(2-Phenyl)phenyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-(2,6-Diethyl-3,5-dichloro)phenyl-carbamoyl-6-azaandrost-4-en-3-o ne
17.beta.-N-(2,6-Diethyl-3-chloro)phenyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-(2-t-Butyl)phenyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-(2,4,6-Trichloro)phenyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-(2-Bromo-5-trifluoromethyl)phenyl-carbamoyl-6-azaandrost-4-en-3- one
17.beta.-N-(2-t-Butyl-6-methyl)phenyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-1-(4-Chlorophenyl)cyclopentyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-(2,6-Dibromo-4-chloro)phenyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-(2,6-Diethyl-4-bromo)phenyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-(2-Bromo-4-t-butyl)phenyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-(2-Chloro-4-t-butyl)phenyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-(5-Bromo-2-t-butyl)phenyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-(5-Chloro-2-t-butyl)phenyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-(2,6-Diethyl)phenyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-(4-Bromo-2-t-butyl)phenyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-(2-t-Butyl-5-cyano)phenyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-(2-(O-4-Tolyl)-5-trifluoromethyl)phenyl-carbamoyl-6-azaandrost-4 -en-3-one
17.beta.-N-(2-(O-4-Chlorophenyl)-5-trifluoromethyl)phenyl-carbamoyl-6-azaan drost-4-en-3-one
17.beta.-N-(2-Nitro-4-t-butyl)phenyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-(2-(O-Phenyl)-5-(1,1-dimethyl)propyl)phenyl-carbamoyl-6-azaandro st-4-en-3-one
17.beta.-N-(2-Ethylsulfonyl-5-trifluoromethyl)phenyl-carbamoyl-6-azaandrost -4-en-3-one
17.beta.-N-(3,5-Di-t-butyl)phenyl-carbamoyl-6-azaandrost-4-en-3-one
1.beta. -N-(2-t-Butyl-5-trifluoromethyl)phenyl-carbamoyl-6-azaandrost-4-en- 3-one
17.beta.-N-(2-t-Butyl-5-phenyl)phenyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-(2,6-Di-i-propyl)phenyl-carbamoyl-6-azaandrost-1,4-dien-3-one
17.beta.-N-(2,6-Di-i-propyl)phenyl-carbamoyi-6-azaandrost4-methyl-1,4-dien- 3-one
17.beta.-N-1-(4-Trifluoromethylphenyl)cyclopentyl-carbamoyl-6-azaandrost-4- en-3-one
17.beta.-N-1-(4-Fluorophenyl)cyclohexyl-carbamoyl-6azaandrost-4-en-3-one
17.beta.-N-1-(4-Methoxyphenyl)cyclohexyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-1-(4-Methoxyphenyl)cyclopentyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-(2,5-bis(Trifluoromethyl))phenyl-carbamoyl-6-azaandrost-4-methyl -4-en-3-one
17.beta.-N-(2t-Butyl-5trifurmethy)phenyl-carbamoyl-6azaandrost4-methyl-4en3 -one
17.beta.-N-(2,5-Di-t-butyl)phenyl-carbamoyl-6-azaandrost-4-methyl-4-en-3-on e
17.beta.-N-(2-t-Butyl-5-(4-chlorophenyl))phenyl-carbamoyl-6-azaandrost-4-en -3-one
17.beta.-N-1-(4-t-Butylphenyl)cyclopentyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-1-(4-t-Butylphenyl)cyclohexyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-1-(4-Chlorophenyl)cyclopentyl-carbamoyl-6-azaandrost-4-methyl-4- en-3-one
17.beta.-N-(2,5-bis(Trifluoromethyl))phenyl-carbamoyl-6-azaandrost-4-chloro -4-en-3-one
17.beta.-N-(2-t-Butyl-5trifurmethyl)phenyl-carbamoyl6azaandrost-4-chloro-4e n-3-one
17.beta.-N-1-(4-t-Butylphenyl)cycloheptyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-1-(4-t-Butylphenyl)cyclohexyl-carbamoyl-6-azaandrost-4-chloro-4- en-3-one
17.beta.-N-(2,6-Diethyl-4-(4-chlorophenyl))phenyl-carbamoyl-6-azaandrost-4- en-3-one
17.beta.-N-4-(4-t-Butylphenyl)tetrahydrothiopyranyl-carbamoyl-6-azaandrost- 4-en-3-one
17.beta.-N-9-(4-t-Butylphenyl)bicyclo›3.3.1!nonyl-carbamoyl-6-azaandrost-4- en-3-one
17.beta.-N-4-(4-t-Butylphenyl)tetrahydropyranyl-carbamoyl-6-azaandrost-4-en -3-one
17.beta.-N-1-(4-Chlorophenyl)cyclohexyl-carbamoyl-6-azaandrost-4-en-3-one
17.beta.-N-(2-t-Butyl-5-(4-t-butyl)phenyl)phenyl-carbamoyl-6-azaandrost-4-e n-3-one or
1.beta. -N-1-(4-Chlorophenyl)cyclopentyl-carbamoyl-6-azaandrost-4-chloro-4- en-3-one
or a pharmaceutically acceptable salt or solvate thereof.

### Claim 25

17.beta.-N-(2-t-Butyl-5-trifluoromethyl)phenyl-carbam oyl-6-azaandrost-4-en-3-one or a pharmaceutically acceptable salt or solvate thereof.

### Claim 26

A compound of formula (I) ##STR27## wherein R.sup.1 and R.sup.2 are,
i) independently hydrogen or lower alkyl and the bond between the carbons bearing R.sup.1 and R.sup.2 is a single or a double bond, or
ii) taken together are a --CH.sub.2 -- group to form a cyclopropane ring, and the bond between the carbons bearing R.sup.1 and R.sup.2 is a single bond;
R.sup.3 is hydrogen or lower alkyl;
R.sup.4 is hydrogen or lower alkyl'
X is, ##STR28## wherein R.sup.10, R.sup.11, R.sup.12 and R.sup.13 are independently hydrogen or lower alkyl, p and q are independently either 0 or 1;
Y is hydrogen; and
Z is --COR.sup.5, CONR.sup.14 R.sup.15, --CH.sub.2 OCO.sub.2 R.sup.5, --CH.sub.2 OCOR.sup.5, --CH.sub.2 NR.sup.5 'COR.sup.5, --CONR.sup.5 NR.sup.14 R.sup.15, --CH.sub.2 NR.sup.5 CONR.sup.14 R.sup.5, or --CON.sup.5 CONR.sup.14 R.sup.15 wherein R.sup.5 and R.sup.5 ' are independently hydrogen, lower alkyl optionally substituted independently with one or more Ar.sup.2 groups (lower alkyl)n-lower cycloalkyl, menthyl, adamantyl, norbornyl or Ar.sup.2 ;
Ar.sup.2 is phenyl group optionally substituted independently with one or more --Alk-H (optionally substituted independently with one or more halogens), --OR.sup.16, --S(O).sub.r R.sup.7, phenyl, methylenedioxy, ethylenedioxy, morpholino, thiomorpholino, cyano, nitro or halogen groups;
Alk is lower alkylene, lower alkenylene or lower alkynylene;
n is 0 or 1;
r is 0, 1 or 2;
R.sup.7 is --Alk-H, --(Alk).sub.n -phenyl or lower cycloalkyl;
R.sup.6 is --Alk-H (optionally substituted independently with one or more halogens), lower cycloalkyl (optionally substituted independently with one or more halogens, or --Alk-H (optionally substituted independently with one or more halogens)) or --(Alk)n-phenyl (wherein phenyl is optionally substituted independently with one or more lower alko, cyano, halogen or --Alk-H groups (optionally substituted independently with one or more halogens));
R.sup.14 is hydrogen or hydroxy, and R.sup.5 is hydrogen, lower cycloalkyl, (optionally substituted independently with one or more R.sup.7 or Ar.sup.2 groups), --(Alk)-adamantyl, --(Alk).sub.n -myrantyl, --(Alk).sub.n -norbornyl, --(Alk).sub.n -fluorenyl, --(Alk).sub.n -indanyl, --Alk-H (optionally substituted independently with one or more lower cycloalkyl, SR.sup.5, OR.sup.5, Ar.sup.2 or Ar.sup.3 groups), Ar.sup.2 or Ar.sup.3, or R.sup.14 and R.sup.15 taken together with the linking nitrogen form a pyrrolidinyl, piperidinyl or perhydroazepinyl ring optionally substituted with one or more R.sup.7 groups; Ar.sup.3 is a pyrrolyl, thienyl, furyl or pyridyl group optionally substituted independently with one or more Alk-H groups; with the provisos that
when Z is COR.sup.5, R.sup.5 is substituted lower alkyl, lower alkyl lower cycloalkyl, menthyl, norbornyl or Ar.sup.2 ;
when Z is CONR.sup.14 R.sup.15 and R.sup.15 is hydrogen, --Alk-H, lower cycloalkyl, lower lakoxy, adamantyl, phenyl, benzyl, diphenylmethyl, triphenylmethyl or --(Alk).sub.n -norbornyl, R.sup.14 is hydroxy; and
when Z is CONR.sup.14 R.sup.15 and R.sup.14 andR.sup.15 taken together with the linking nitrogen form a pyrrolidinyl, piperidinyl or pergydroazepinyl ring, said ring is substituted with one or more lower alkenyl, lower alkynyl, --(Alk).sub.n -phenyl or lower cycloalkyl groups; or a pharmaceutically acceptable salt or solvate thereof.

### Claim 27

A compound of formula (I) ##STR29## wherein: R.sup.1 and R.sup.2 are,
i) independently hydrogen or lower alkyl and the bond between the carbons bearing R.sup.1 and R.sup.2 is a single or a double bond, or
ii) taken together are a --C H.sub.2 -- group to form a cyclopropane ring, and the bond between the carbons bearing R.sup.1 and R.sup.2 is a single bond;
R.sup.3 is hydrogen, --Alk.sup.1 --H , --Alk.sup.1 --H substituted with one or more halogens, lower cycloalkyl, lower cycloalkyl-lower alkyl, halogen, --(Alk.sup.1).sub.n --CO.sub.2 H, --(Alk.sup.1).sub.n --CO.sub.2 R.sup.7, --(Alk.sup.1).sub.n --Ar.sup.1, --(Alk.sup.1).sub.n --CONR.sup.8 R.sup.9, --(Alk.sup.1).sub.n --NR.sup.8 R.sup.9, --(Alk.sup.1).sub.n --S(O).sub.r R.sup.7, --(Alk.sup.1).sub.n --CN, --(Alk.sup.1)--OH or --(Alk.sup.1).sub.n --OR.sup.7 ; wherein
Alk.sup.1 is lower alkylene, lower alkenylene or lower alkynylene,
n is 0or 1,
r is0,1or 2,
R.sup.7 is --Alk.sup.1 --H, --(Alk.sup.1).sub.n --Ar.sup.1 or lower cycloalkyl,
R.sup.8 and R.sup.9 are independently hydrogen, --Alk.sup.1 --H or lower cycloalkyl,
Ar.sup.1 is a homocyclic aryl group of 6 to 14 carbons;
R.sup.4 is hydrogen, --Alk.sup.1 --H, lower cycloalkyl, lower cycloalkyl-lower alkyl, --(Alk.sup.1).sub.n --S(O).sub.r R.sup.7, --(Alk.sup.1).sub.n -phthalimidyl, (--Alk.sup.1)--CO.sub.2 H, --(Alk.sup.1).sub.n --CO.sub.2 R.sup.7, --(Alk.sup.1).sub.n --Ar.sup.1, --(Alk.sup.1).sub.n --CONR.sup.8 R.sup.9, --(Alk.sup.1).sub.n --NR.sup.8 R.sup.9, --(Alk.sup.1).sub.n --OH or --(Alk.sup.1).sub.n --OR.sup.7 ;
X is, ##STR30## wherein R.sup.10, R.sup.11, R.sup.12 and R.sup.13 are independently hydrogen or lower alkyl, p and q are independently either 0or 1;
Y and Z are,
i) Y is hydrogen or hydroxy and
Z is --(Alk.sup.2).sub.n --COR.sup.5, --(Alk.sup.2).sub.n --CO.sub.2 R.sup.5, --(Alk.sup.2).sub.n --COSR.sup.5, --(Alk.sup.2).sub.n --CONR.sup.14 R.sup.15, --(Alk.sup.2)--OCOR.sup.5, --(Alk.sup.2)--OCONR.sup.14 R.sup.15, --(Alk.sup.2)--OR.sup.5, --(Alk.sup.2)--NR.sup.5 COR.sup.5, --(Alk.sup.2)--NR.sup.5 CO.sub.2 R.sup.5, --(Alk.sup.2)--NR.sup.5 CONR.sup.14 R.sup.15, --(Alk.sup.2)--.sub.n CONR.sup.5 NR.sup.14 R.sup.15, --(Alk.sup.2).sub.n --CONR.sup.5 CONR.sup.14 R.sup.15, (--Alk.sup.2 -)NR.sup.5 CSNR.sup.14 R.sup.15 or --(Alk.sup.2).sub.n --CONR.sup.5 CSNR.sup.14 R.sup.15 ; wherein
Alk.sup.2 is (C.sub.1-12) alkylene, (C.sub.2-12) alkenylene or (C.sub.2-12) alkynylene, R.sup.5 is hydrogen, --Alk.sup.1 --H, --(Alk.sup.1).sub.n -(lower cycloalkyl), adamantyl, --(Alk.sup.1).sub.n --Ar.sup.2, --(Alk.sup.1).sub.n --Ar.sup.3, (lower cycloalkyl).sub.n Ar.sup.2, (lower cycloalkyl).sub.n Ar.sup.3 or --Alk.sup.1 -substituted independently with one or more CO.sub.2 H, CO.sub.2 R.sup.7, Ar.sup.2 or Ar.sup.3 groups; wherein
Ar.sup.2 is an aromatic group of 6 to 14 carbon ring atoms, optionally substituted with one or more Alk.sup.1, Alk.sup.1 substituted with one or more halogens, --(Alk.sup.1).sub.n -OH, --(Alk.sup.1).sub.n --OR.sup.7, --(Alk.sup.1).sub.n --CO.sub.2 H, --(Alk.sup.1).sub.n --CO.sub.2 R.sup.7, S(O).sub.r R.sup.7 or NR.sup.8 R.sup.9, lower cycloalkyl, lower alkoxy, --(Alk.sup.1).sub.n --Ar.sup.1, methylenedioxy, ethylenedioxy, morpholino, thiomorpholino, cyano or halogen groups;
Ar.sup.3 is an aromatic group of 5 to 14 ring atoms, at least one of which is O, N or S, optionally substituted with one or more Alk.sup.1, lower cycloalkyl, lower alkoxy, CO.sub.2 H, CO.sub.2 R.sup.7, --(Alk.sup.1).sub.n --Ar.sup.1, cyano or halogen groups;
R.sup.14 and R.sup.15 are,
a) independently, hydrogen or --Alk.sup.2 -H, lower cycloalkyl, lower alkoxy, adamantyl, --(Alk.sup.1).sub.n -norbornyl, Ar.sup.2, Ar.sup.3, --Alk.sup.1 -substituted independently with one or more SR.sup.5, COR.sup.5, CONR.sup.5 R.sup.7, NR.sup.5 COR.sup.5, NR.sup.5 CO.sub.2 R.sup.5, NR.sup.5 CONHR.sup.5, CO.sub.2 R.sup.5, OR.sup.5, Ar.sup.2 or Ar.sup.3 groups, --(Alk.sup.1).sub.n -fluorenyl, or --(Alk.sup.1).sub.n -indanyl; or
b) carbon atoms, optionally substituted with one or more lower alkyl groups, taken together with the linking nitrogen to form a 4 to 8 atom heterocyclic group ##STR31## wherein; Her represents --O--, --CH.sub.2 --, --S(O).sub.r --, --(NH)--or --(N(Alk.sup.1))--;
with the proviso that
when Z is (--Alk.sup.2 -).sub.n COR.sup.5, (--Alk.sup.2 -).sub.n CO.sub.2 R.sup.5 or --(Alk.sup.2).sub.n -CO-thiopyridyl and R.sup.5 is hydrogen, --Alk.sup.1 --H, lower cycloalkyl, --(Alk.sup.1).sub.n --Ar.sup.1, adamantyl or
when Z is (--Alk.sup.2 -).sub.n CONR.sup.14 R.sup.15 and R.sup.14 and R.sup.15 are
(a) independently hydrogen, --Alk.sup.2 -H, lower cycloalkyl, lower alkoxy, adamantyl, -Ar.sup.1, benzyl, diphenylmethyl, triphenylmethyl or --(Alk.sup.1).sub.n -norbornyl; or
(b) carbon atoms, optionally substituted with one or more lower alkyl groups, taken together with the linking nitrogen to form a 4 to 8 atom heterocylic ring as herein before defined,
Y is hydroxy;
ii) Y is hydrogen and
Z is OR.sup.5, OCOR.sup.5, OCONR.sup.14 R.sup.15, NR.sup.5 COR.sup.5, NR.sup.5 CO.sub.2 R.sup.5, NR.sup.5 CONR.sup.14 R.sup.15 or NR.sup.5 CSR.sup.14 R.sup.15 ;
iii) Y and Z taken together are .dbd.O, .dbd.CH--(Alk.sup.1).sub.n --COR.sup.5, .dbd.CH--(Alk.sup.1).sub.n --CO.sub.2 R.sup.5 or .dbd.CH--(Alk.sup.1).sub.n --CONR.sup.14 R.sup.15 ;
R.sup.6 is hydrogen or methyl;
and pharmaceutically acceptable salts thereof.

### Claim 28

A compound of formula (I): ##STR32## wherein R.sup.1 and R.sup.2
i) are independently hydrogen or lower alkyl and the bond between the carbons bearing R.sup.1 and R.sup.2 is a single or a double bond, or
ii) taken together are a --CH.sub.2 -- group forming a cyclopropane ring, and the bond between the carbons bearing R.sup.1 and R.sup.2 is a single bond; R.sup.3 is, hydrogen, --Alk.sup.1 --H (optionally substituted with one or more halogens), lower cycloalkyl, lower cycloalkyl-lower alkyl), halogen, --(Alk.sup.1).sub.n --CO.sub.2 H, --(Alk.sup.1).sub.n --CO.sub.2 R.sup.7, --(Alk.sup.1).sub.n --Ar.sup.1, --(Alk.sup.1).sub.n --CONR.sup.8 R.sup.9, --(Alk.sup.1).sub.n --NR.sup.8 R.sup.9, --(Alk.sup.1).sub.n --S(O).sub.r R.sup.7, --(Alk.sup.1).sub.n --CN, --(Alk.sup.1)--OH, --(Alk.sup.1).sub.n --COR.sup.7 or --(Alk.sup.1).sub.n --OR.sup.7 ; wherein
Alk.sup.1 is lower alkylene, lower alkenylene or lower alkynylene,
n is 0 or 1,
r is 0, 1 or 2,
R.sup.7 is --Alk.sup.1 --H, --(Alk.sup.1).sub.n --Ar.sup.1 or lower cycloalkyl,
R.sup.8 and R.sup.9 are independently hydrogen, --Alk.sup.1 --H or lower cycloalkyl,
Ar.sup.1 is a homocyclic aryl group of 6 to 14 carbons;
R.sup.4 is, hydrogen, --Alk.sup.1 --H, lower cycloalkyl, lower cycloalkyl-lower alkyl, --(Alk.sup.1).sub.n --S(O).sub.r R.sup.7, --(Alk.sup.1).sub.n -phthalimidyl, --(Alk.sup.1)--CO.sub.2 H, --(Alk.sup.1).sub.n --CO.sub.2 R.sup.7, --(Alk.sup.1).sub.n --COR.sup.7, --(Alk.sup.1).sub.n --Ar.sup.1, --(Alk.sup.1).sub.n --CONR.sup.8 R.sup.9, --(Alk.sup.1).sub.n --NR.sup.8 R.sup.9, --(Alk.sup.1).sub.n --OH or --(Alk.sup.1).sub.n --OR.sup.7 ;
X is, ##STR33## wherein R.sup.10, R.sup.11, R.sup.12 and R.sup.13 are independently hydrogen or lower alkyl, p and q are independently either 0or 1; and,
i) Y is hydrogen or hydroxy and
Z is --(Alk.sup.2).sub.n --COR.sup.5, --(Alk.sup.2).sub.n --CO.sub.2 R.sup.5, --(Alk.sup.2).sub.n --COSR.sup.5, --(Alk.sup.2).sub.n -CONR.sup.14 R.sup.15, --(Alk.sup.2)--OCO.sub.2 R.sup.5, --(Alk.sup.2)--OCOR.sup.5, --(Alk.sup.2)--OCONR.sup.14 R.sup.15, --(Alk.sup.2)--OR.sup.5, --(Alk.sup.2)--NR.sup.5 'COR.sup.5, --(Alk.sup.2)--NR.sup.5 'CO.sub.2 R.sup.5, --(Alk.sup.2)--NR.sup.5 CONR.sup.14 R.sup.15, --(Alk.sup.2).sub.n --CONR.sup.5 NR.sup.14 R.sup.15, --(Alk.sup.2).sub.n --CONR.sup.5 CONR.sup.14 R.sup.15, --(Alk.sup.2)--NR.sup.5 CSNR.sup.14 R.sup.15 or --(Alk.sup.2).sub.n --CONR.sup.5 CSNR.sup.14 R.sup.15 ; wherein
Alk.sup.2 is (C.sub.1-12) alkylene, (C.sub.2-12) alkenylene or (C.sub.2-12) alkynylene, R.sup.5 and R.sup.5 ' are independently hydrogen, --Alk.sup.1 --H (optionally substituted independently with one or more CO.sub.2 H, CO.sub.2 R.sup.7, Ar.sup.2, Ar.sup.3 or cyano groups), --(Alk.sup.1).sub.n -(lower cycloalkyl (optionally substituted independently with one or more --Alk.sup.1 --H groups)), adamantyl, norbornyl, Ar.sup.2, Ar.sup.3, (lower cycloalkyl)-Ar.sup.2 or (lower cycloalkyl)-Ar.sup.3 ;
wherein
Ar.sup.2 is a homocyclic aromatic group of 6 to 14 carbon ring atoms (optionally substituted independently with one or more --Alk.sup.2 -H (optionally substituted independently with one or more halogens), --(Alk.sup.1).sub.n --OH, --(Alk.sup.1).sub.n --OR.sup.16, --(Alk.sup.1).sub.n --Ar.sup.3, --(Alk.sup.1).sub.n --CO.sub.2 H, --(Alk.sup.1).sub.n --CO.sub.2 R.sup.7, S(O).sub.r R.sup.7, NR.sup.8 S(O).sub.r R.sup.16, NR.sup.8 R.sup.9, CONR.sup.8 R.sup.9, lower cycloalkyl, lower alkoxy, --(Alk.sup.1).sub.n --Ar.sup.1, methylenedioxy, ethylenedioxy, morpholino, thiomorpholino, cyano, nitro or halogens); wherein
R.sup.16 is --Alk.sup.1 --H (optionally substituted independently with one or more halogens), lower cycloalkyl (optionally substituted independently with one or more halogens, or --Alk.sup.1 --H (optionally substituted independently with one or more halogens)) or --(Alk.sup.1).sub.n --Ar.sup.1 (wherein Ar.sup.1 is optionally substituted independently with one or more, lower alkoxy, cyano groups, halogens or --Alk.sup.1 --H (optionally substituted independently with one or more halogens));
Ar.sup.3 is an aromatic group of 5 to 14 ring atoms, at least one of which is O, N or S, (optionally substituted independently with one or more --Alk.sup.1 --H (optionally substituted independently with one or more halogens), lower cycloalkyl, lower alkoxy, CO.sub.2 H, CO.sub.2 R.sup.7, --(Alk.sup.1).sub.n -Ar.sup.1, cyano or halogen);
R.sup.14 and R.sup.15 are,
a) independently, hydroxy, hydrogen, --Alk.sup.2 - H, lower cycloalkyl (optionally substituted independently with one or more cyano, R.sup.16, Ar.sup.2, Ar.sup.3), lower alkoxy, --(Alk.sup.1).sub.n -adamantyl, --(Alk.sup.1).sub.n -myrantyl, --(Alk.sup.1).sub.n -norbornyl, --(Alk.sup.1).sub.n -fluorenyl, --(Alk.sup.1).sub.n -indanyl, --Alk.sup.1 --H (optionally substituted independently with one or more, halogens, cyano, cycloalkyl, SR.sup.5, COR.sup.5, CONR.sup.5 R.sup.7, NR.sup.5 'COR.sup.5, NR.sup.5 'CO.sub.2 R.sup.5, NR.sup.5 'CONHR.sup.5, CO.sub.2 R.sup.5, OR.sup.5, Ar.sup.2 or Ar.sup.3), Ar.sup.2 or Ar.sup.3 ;
b) alkylene groups (optionally substituted with one or more R.sup.7 groups, taken together with the linking nitrogen to form a 4 to 8 atom heterocyclic group) ##STR34## wherein; Her represents --O--, --CH.sub.2 --, --S(O).sub.r --, --(NH)-- or --(N(Alk.sup.1 --H))--;
with the proviso that
when Z is --(Alk.sup.2).sub.n --COR.sup.5, --(Alk.sup.2).sub.n --CO.sub.2 R.sup.5 or --(Alk.sup.2).sub.n --CO-thiopyridyl and
R.sup.5 is hydrogen, --Alk.sup.1 --H, lower cycloalkyl, --(Alk.sup.1).sub.n --Ar.sup.1, adamantyl or
when Z is --(Alk.sup.2).sub.n --CONR.sup.14 R.sup.15 and
R.sup.14 and R.sup.15 are
a) independently hydrogen, --Alk.sup.2 -H, lower cycloalkyl, lower alkoxy, adamantyl, --Ar.sup.1, benzyl, diphenylmethyl, triphenylmethyl or --(Alk.sup.1).sub.n -norbornyl; or
b) carbon atoms, optionally substituted with one or more lower alkyl groups, taken together with the linking nitrogen to form a 4 to 8 atom heterocylic ring as herein before defined,
Y is hydroxy; or
ii) Y is hydrogen and
Z is OR.sup.5, OCOR.sup.5, OCONR.sup.14 R.sup.15, NR.sup.5 'COR.sup.5 'NR.sup.5 'CO.sub.2 R.sup.5, NR.sup.5 CONR.sup.14 R.sup.15 or NR.sup.5 CSR.sup.14 R.sup.15 ; and
iii) Y and Z taken together are
.dbd.O, .dbd.CH--(Alk.sup.1).sub.n --COR.sup.5, .dbd.CH--(Alk.sup.1).sub.n --CO.sub.2 R.sup.5 or
.dbd.CH--(Alk.sup.1).sub.n --CONR.sup.14 R.sup.15 ;
R.sup.6 is, hydrogen or methyl;
and pharmaceutically acceptable salts thereof.

### Claim 29 (depends on 1)

A pharmaceutical composition comprising a compound of formula (I) as defined in claim 1 together with a pharmaceutically acceptable carrier.

### Claim 30 (depends on 1)

A method of inhibiting testosterone-5.alpha.-reductases comprising contacting testosterone-5.alpha.-reductases with a compound of formula (I) as defined in claim 1.

### Claim 31 (depends on 1)

A method of treatment of androgen responsive or mediated disease comprising administering an effective amount of a compound of formula (I) as defined in claim 1 to a patient in need thereof in combination.

### Claim 32 (depends on 1)

A method of treatment of androgen responsive or mediated disease comprising administering an effective amount of a compound of formula (I) as defined in claim 1 to a patient in need thereof in combination with an antiandrogen.

### Claim 33 (depends on 1)

A method of treatment of androgen responsive or mediated disease comprising administering an effective amount of a compound of formula (I) as defined in claim 1 to a patient in need thereof in combination with an alpha 1 adrenergic receptor blocker.

### Claim 34 (depends on 1)

A method of treatment of androgen responsive or mediated disease comprising administering an effective amount of a compound of formula (I) as defined in claim 1 to a patient in need thereof in combination with an antiestrogen.

### Claim 35 (depends on 31)

A method of treatment as claimed in claim 31 wherein the androgen responsive or mediated disease is benign prostatic hyperplasia, prostatitis, prostate cancer, acne, male pattern baldness and hirsutism.

### Claim 36 (depends on 1)

A process for preparing a compound of formula (I) as defined in claim 1 or a pharmaceutically acceptable salt or solvate thereof which comprises (A) reacting a compound of formula (IX) ##STR35## Wherein JO is hydroxy or a protected hydroxygroup, with an oxidismagent.

### Claim 37 (depends on 36)

A process as claimed in claim 36 wherein a compound of formula (IX) wherein JO is a protected hydroxy group is deprotected and then oxidised with an appropriate oxidising agent to give a compound of formula (I) where R.sup.4 is hydrogen.

### Claim 38 (depends on 37)

A process as claimed in claim 37 wherein the oxidising agent is Jones reagent.

### Claim 39 (depends on 36)

A process as claimed in claim 36 wherein a compound of formula (IX) wherein JO is a protected hydroxy group is treated with an acylating agent, deprotected and then oxidised with an appropriate oxidising agent to give a compound of formula (I) where R.sup.4 is acyl.

### Claim 40 (depends on 39)

A process as claimed in claim 39 wherein the oxidising agent is pyridinium dichromate.