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US 5,041,433 AGranted
11-keto or hydroxy 3,5-diene steroids as inhibitors of steriod 5-.alpha.-reductase
AssigneeSmithKline Beecham Corporation
InventorsDennis A. Holt, Brian W. Metcalf, Mark A. Levy
Life of this patent
Estimating the term…
Abstract
Invented are carboxyl and carboxyl alkyl ester substituted 11-keto and hydroxy analogues of synthetic steroidal compounds, pharmaceutical compositions containing these compounds, and methods of using these compounds to inhibit steroid 5-.alpha.-reductase.
Claims28
A compound represented by the Formula (I) ##STR11## in which:
- the D ring has an optional double bond where indicated by the broken line, provided that the D ring does not have a C.sub.16 -C.sub.17 double bond when R.sup.2 represents two substituents or a divalent substituent;
- X is
- (2) keto, or
- (2) a hydrogen atom and a hydroxyl group;
- R.sup.1 is H or C.sub.1-8 alkyl;
- and
- R.sup.2 is
- (1) .alpha.-hydrogen, .alpha.-hydroxyl, or .alpha.-acetoxy and/or ##STR12## where W is a bond or C.sub.1-12 alkyl, and R.sup.3 is (i) C.sub.1-8 alkyl,
- (ii) C.sub.1-8 alkoxy, or
- (iii) N(R.sup.4).sub.2, where each R.sup.4 is independently selected from hydrogen, C.sub.1-8 alkyl, C.sub.3 -6cycloalkyl, phenyl;
- or both R.sup.4 taken together with the nitrogen to which they are attached represent a 5-6 membered saturated ring comprising up to one other heteroatom selected from oxygen and nitrogen;
- (2) .dbd.CH--W--CO--R.sup.3 or .dbd.CH--W--OR.sup.5, where W and R.sup.3 have the same meaning as above, and R.sup.5 is
- (i) phenylC.sub.1-6 alkylcarbonyl,
- (ii) C.sub.5-10 cycloalkylcarbonyl,
- (iii) benzoyl,
- (iv) C.sub.1-8 alkoxycarbonyl,
- (v) aminocarbonyl, or C.sub.1-8 alkyl substituted aminocarbonyl,
- (vi) C.sub.1-8 alkyl, or
- (vii) C.sub.1-20 alkylcarbonyl;
- (3) .alpha.-hydrogen and .beta.-NHCOR.sup.6 where R.sup.6 is C.sub.1-12 alkyl or .beta.-N(R.sup.4).sub.2 where R.sup.4 has the same meaning as above, or
- (4) keto;
- or a pharmaceutically acceptable salt thereof.
19 more elements
A compound of the Formula (II) ##STR13## in which:
- the D ring has an optional double bond where indicated by the broken line, provided that the D ring does not have a C.sub.16 -C.sub.17 double bond when R.sup.7 represents two substituents or a divalent substituent;
- R.sup.7 is
- (1) .alpha.-hydrogen, .alpha.-hydroxyl, or .alpha.-acetoxy and/or ##STR14## where W is a bond or C.sub.1-12 alkyl, and R.sup.3 is (i) C.sub.1-8 alkyl,
- (ii) C.sub.1-8 alkoxy, or
- (iii) N(R.sup.4).sub.2, where each R.sup.4 is independently selected from hydrogen, C.sub.1-8 alkyl, C.sub.3-6 cycloalkyl, phenyl;
- or both R.sup.4 taken together with the nitrogen to which they are attached represent a 5-6 membered saturated ring comprising up to one other heteroatom selected from oxygen and nitrogen;
- (2) .dbd.CH--W--CO--R.sup.3 or .dbd.CH--W--OR.sup.5, where W and R.sup.3 have the same meaning as above, and R.sup.5 is
- (i) phenylC.sub.1-6 alkylcarbonyl,
- (ii) C.sub.5 -10cycloalkylcarbonyl,
- (iii) benzoyl,
- (iv) C.sub.1-8 alkoxycarbonyl,
- (v) aminocarbonyl, or C.sub.1-8 alkyl substituted aminocarbonyl,
- (vi) C.sub.1-8 alkyl, or
- (vii) C.sub.1-20 alkylcarbonyl;
- (3) .alpha.-hydrogen and .beta.-NHCOR.sup.6 where R.sup.6 is C.sub.1-12 alkyl or .beta.-N(R.sup.4).sub.2 where R.sup.4 has the same meaning as above;
- (4) keto;
- or
- (5) moieties which can be chemically converted to moieties (1) through (4) above.
15 more elements
Dependencies are inferred from the claim text.