US 5,095,129 A · 19,11 .beta.-bridged steroids, their manufacture and pharmaceutical preparations containing them

Abstract

New 19,11.beta.-bridged steroids of the general formula I ##STR1## where R.sup.1 stands for a methyl or ethyl radical, R.sup.2 for a hydrogen or chlorine atom or a C.sub.1 -C.sub.4 -alkyl radical, B and G, which are the same or different, respectively for a hydrogen atom, a C.sub.1 -C.sub.4 -alkyl radical or, together, for a second bond between the carbon atoms 6 and 7, B and R.sup.2 together for a methylene or an ethylene group, Z for the radical of a pentagonal or hexagonal ring, which is possibly substituted and possibly unsaturated, V stands for a possibly substituted carbocyclic or heterocyclic aryl radical, the ring A for ##STR2## M and N together meaning a second bond or M a hydrogen atom and N a hydroxy group, X means an oxygen atom, two hydrogen atoms or a hydroxyimino grouping N.about.OH, R.sup.3 and D, which are the same or different, respectively a hydrogen atom, a nitrile radical or a C.sub.1 -C.sub.4 -alkyl radical or, together, a methylene or ethylene group, E a hydrogen atom or a C.sub.1 -C.sub.4 -alkyl radical, D and E together meaning a second bond between carbon atoms 1 and 2 or together a methylene group ##STR3## with R.sup.11 in the meaning of a hydrogen atom or a C.sub.1 -C.sub.8 -alkyl radical, are described as well as their pharmaceutically tolerated addition salts with acids. The new compounds possess valuable pharmacological properties.

Claims27

Dependent claims

A 19, 11.beta.-bridged steroid of general formula I ##STR20## wherein R.sup.1 is a methyl or ethyl radical;

R.sup.2 is hydrogen, chlorine or C.sub.1 -C.sub.4 -alkyl radical;
B and G, being the same or different, are each hydroge or C.sub.1 -C.sub.4 -alkyl radical;
B and G, together, can also be a second bond between carbon atoms 6 and 7;
B and R.sup.2, together, can also be a methylene or ethylene group;
Z is a substituted or unsubstituted, saturated or unsaturated, 5- or 6-member ring;
V is an unsubstituted or substituted, carbocyclic or heterocyclic, aryl radical;
ring A is ##STR21## wherein M and N, together, are a second bond, or M is hydrogen and N is hydroxy, in which case B, R.sup.2, G, R.sup.3, D and E are all each hydrogen.
X is an oxygen atom, two hydrogen atoms or one hydroxyimino group (N.about.OH),
R.sup.3 and D, being the same or different, are each hydrogen nitrile, or C.sub.1 -C.sub.4 -alkyl radical,
R.sup.3 and D, together, can also be a methylene or ethylene group,
E is hydrogen or C.sub.1 -C.sub.4 -alkyl radical,
D and E, together, can also be a second bond between carbon atoms 1 and 2 or, together, can also be a methylene group;
or Ring A is ##STR22## or Ring A is ##STR23## wherein R.sup.11 is hydrogen or C.sub.1 -C.sub.8 -alkyl radical;
and pharmaceutically tolerated acid addition salts thereof.

11 more elements

A 19, 11.beta.-bridged steroid of general formula I ##STR28## wherein R.sup.1 is a methyl or ethyl radical;

R.sup.2 is hydrogen, chlorine or C.sub.1 -C.sub.4 -alkyl radical;
B and G, being the same or different, are each hydrogen or C.sub.1 -C.sub.4 -alkyl radical;
B and G, together, can also be a second bond between carbon atoms 6 and 7;
B and R.sup.2, together, can also be a methylene or ethylene group;
Z is a ring according to the formula ##STR29## wherein -- is a single bond or a double bond;
W is CH.sub.2 --, CH--, CH.sub.2 CH.sub.2 -- or CHCH.sub.2 --;
and
R.sup.5 and R.sup.6 are, respectively, --OR.sup.7 and --C.tbd.C--U, ##STR30## --OR.sup.7 and --(CH.sub.2).sub.m --CH.sub.2 --R.sup.9, --OR.sup.7 and --CH.dbd.CH--(CH.sub.2).sub.k --CH.sub.2 --R.sup.9, --OR.sup.10 and --H, or --OR.sup.10 and --(CH.sub.2).sub.k --C.tbd.C--U, or R.sup.5 and R.sup.6 together are ##STR31## R.sup.7 is hydrogen or C.sub.1 -C.sub.4 -acyl radical, U is hydrogen, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -hydroxyalkyl, C.sub.1 -C.sub.4 -alkoxyalkyl, C.sub.1 -C.sub.4 -aclyoxyalkyl, or halogen,
R.sup.8 is hydrogen, hydroxy, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -O-alkyl, or C.sub.1 -C.sub.4 -O-acyl,
R.sup.9 is hydrogen, hydroxy, cyanide, a C.sub.1 -C.sub.4 -alkyl, or C.sub.1 -C.sub.4 -O-acyl,
R.sup.10 is hydrogen, C.sub.1 -C.sub.10 -alkyl, or C.sub.1 -C.sub.10 -acyl,
m is 0, 1, 2 or 3, and
k is 0, 1 or 2;
V is a 5- or 6-member heteroaromatic ring with 1 to 2N, O or S atoms of the formula ##STR32## or V is a phenyl ring according to the formula ##STR33## wherein R.sup.4 and R.sup.4', being the same or different, are each hydrogen, cyanide, --OR.sup.11, --S(O).sub.k R.sup.11, N(O).sub.n R.sup.11 R.sup.12 --;
--O--SO.sub.2 R.sup.13, --P(O) (OR.sup.14).sub.2, SiR.sup.14.sub.3 -- or SnR.sup.14.sub.3 --;
R.sup.11 is hydrogen or C.sub.1 -C.sub.8 -alkyl radical;
R.sup.12 is R.sup.11, cyanide or C.sub.1 -C.sub.10 -acyl radical;
R.sup.13 is perfluorated C.sub.1 -C.sub.4 -alkyl radical;
R.sup.14 is C.sub.1 -C.sub.4 -alkyl radical;
R.sup.11 and R.sup.12, in an --N(O).sub.n R.sup.11 R.sup.12 group, can also be, together with the inclusion of N, a 5- or 6-member heterocyclic ring, optionally containing another heteroatom selected from N, O or S;
Y and Y' being the same or different, are each a direct bond, a straight-chain or branched alkylene group having up to 20 carbon atoms, optionally containing double or triple bond(s), and optionally substituted with one or more oxo-, C.sub.1 -C.sub.10 -acyloxy-, --OR.sup.11, --S(O).sub.k R.sup.11 and/or --N(O).sub.n R.sup.11 R.sup.12 groups, or a substituted or unsubstituted aryl radical;
R.sup.4-Y and R.sup.4'-Y', together, can be substituted or unsubstituted, saturated or unsaturated or aromatic, 5- or 6-member ring with 0 to 2 oxygen sulfur atoms and/or --NR.sup.11 -- groups;
k is 0, 1 or 2;
and
n is 0 or 1;
with the proviso that for group V, k and n are greater than 0 only if R.sup.11 is a C.sub.1 -C.sub.8 -alkyl radical;
ring A is ##STR34## wherein M and N, together, are a second bond, or M is hydrogen and N is hydroxy, in which case B, R.sup.2, G, R.sup.3, D and E are all each hydrogen,
X is an oxygen atom, two hydrogen atoms or one hydroxyimino group (N--OH),
R.sup.3 and D, being the same or different, are each hydrogen nitrile, or C.sub.1 -C.sub.4 -alkyl radical,
R.sup.3 and D, together, can also be a methylene or ethylene group,
E is hydrogen or C.sub.1 -C.sub.4 -alkyl radical,
D and E, together, can also be a second bond between carbon atoms 1 and 2 or, together, can also be a methylene group;
or Ring A is ##STR35## or Ring A is ##STR36## wherein R.sup.11 is hydrogen or C.sub.1 -C.sub.8 -alkyl radical;
and pharmaceutically tolerated acid additions salts thereof.

31 more elements

A 19, 11.beta.-bridged steroid of general formula I ##STR37## wherein R.sup.1 is a methyl or ethyl radical;

R.sup.2 is hydrogen, chlorine or C.sub.1 -C.sub.4 -alkyl radical;
B and G, being the same or different, are each hydrogen or C.sub.1 -C.sub.4 -alkyl radical;
B and G, together, can also be a second bond between carbon atoms 6 and 7;
B and R.sup.2, together, can also be a methylene or ethylene group;
Z is a ring according to the formula ##STR38## wherein -- is a single bond or a double bond;
W is CH.sub.2 --, CH--, CH.sub.2 CH.sub.2 -- or CHCH.sub.2 --;
and
R.sup.5 and R.sup.6 are, respectively, --OR.sup.7 and --C.tbd.C--U, ##STR39## --OR.sup.7 and --(CH.sub.2).sub.m --CH.sub.2 --R.sup.9, --OR.sup.7 and --CH.dbd.CH--(CH.sub.2).sub.k --CH.sub.2 --R.sup.9, --OR.sup.10 and --H, or --OR.sup.10 and --(CH.sub.2).sub.k --C.tbd.C--U, or R.sup.5 and R.sup.6 together are ##STR40## wherein R.sup.7 is hydrogen or C.sub.1 -C.sub.4 -acyl radical,
U is hydrogen, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -hydroxyalkyl, C.sub.1 -C.sub.4 -alkoxyalkyl, C.sub.1 -C.sub.4 -acyloxyalkyl, or halogen,
R.sup.8 is hydrogen, hydroxy, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -O-alkyl, or C.sub.1 -C.sub.4 -O-acyl,
R.sup.9 is hydrogen, hydroxy, cyanide, a C.sub.1 -C.sub.4 -alkyl, or C.sub.1 -C.sub.4 -O-acyl
R.sup.10 is hydrogen, C.sub.1 -C.sub.10 -alkyl, or C.sub.1 -C.sub.10 -acyl,
m is 0, 1, 2 or 3, and
k is 0, 1 or 2;
V is a phenyl ring according to the formula ##STR41## wherein R.sup.4 and R.sup.4', being the same or different, are each hydrogen, cyanide, --OR.sup.11, --S(O).sub.k R.sup.11, N(O).sub.n R.sup.11 R.sup.12 --, --O--SO.sub.2 R.sup.13, --P(O) (OR.sup.14).sub.2, SiR.sup.14.sub.3 -- or SnR.sup.14.sub.3 --,
R.sup.11 is hydrogen or C.sub.1 -C.sub.8 -alkyl radical,
R.sup.12 is R.sup.11, cyanide or C.sub.1 -C.sub.10 -acyl radical,
R.sup.13 is perfluorated C.sub.1 -C.sub.4 -alkyl radical,
R.sup.14 is C.sub.1 -C.sub.4 -alkyl radical,
R.sup.11 and R.sup.12, in an --N(O).sub.n R.sup.11 R.sup.12 group, can also be, together with the inclusion of N, a 5- or 6-member heterocyclic ring, optionally containing another heteroatom selected from N, O or S,
Y and Y', being the same or different, are each a direct bond, a straight-chain or branched alkylene group having up to 20 carbon atoms, optionally containing double or triple bond(s), and optionally substituted with one or more oxo-, C.sub.1 -C.sub.10 -acyloxy-, --OR.sup.11, --S(O).sub.k R.sup.11 and/or --N(O).sub.n R.sup.11 R.sup.12 groups, or a substituted or unsubstituted aryl radical,
R.sup.4-Y and R.sup.4'-Y', together, can also be substituted or unsubstituted, saturated or unsaturated or aromatic, 5- or 6-member ring with 0 to 2 oxygen, sulfur atoms and/or --NR.sup.11 -- groups,
k is 0, 1 or 2, and
n is 0 or 1, with the proviso that for group V, k and n are greater than 0 only if R.sup.11 is a C.sub.1 -C.sub.8 -alkyl radical;
ring A is ##STR42## wherein M and N, together, are a second bond, or M is hydrogen and N is hydroxy, in which case B, R.sup.2, G, R.sup.3, D and E are all each hydrogen,
X is an oxygen atom, two hydrogen atoms or one hydroxyimino group (N--OH),
R.sup.3 and D, being the same or different, are each hydrogen nitrile, or C.sub.1 -C.sub.4 -alkyl radical,
R.sup.3 and D, together, can also be a methylene or ethylene group,
E is hydrogen or C.sub.1 -C.sub.4 -alkyl radical,
D and E, together, can also be a second bond between carbon atoms 1 or 2 or, together, can also be a methylene group;
or Ring A is ##STR43## or Ring A is ##STR44## wherein R.sup.11 is hydrogen or C.sub.1 -C.sub.8 -alkyl radical;
and pharmaceutically tolerated acid addition salts thereof.

29 more elements

Dependencies are inferred from the claim text.

19,11 .beta.-bridged steroids, their manufacture and pharmaceutical preparations containing them

Life of this patent

19,11 .beta.-bridged steroids, their manufacture and pharmaceutical preparations containing them

Life of this patent

Abstract

Claims27