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US 5,728,689 AGranted
11.beta.-aryl-4-estrenes, process for their production as well as their use as pharmaceutical agents
AssigneeSchering Corporation
InventorsArwed Cleve, Cornelius Scheidges, Gunter Neef, Eckhard Ottow, Walter Elger, Sybille Beier
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Abstract
A method of inducing an antigestagenic effect by the administration of compounds of formula I: ##STR1## wherein, substituents are as defined in the specification.
Claims26
A method of inducing an antigestagenic effect, comprising administering an antigestagenically effective amount of an 11.beta.-aryl-4-estrene of formula I having progesterone antagonist activity ##STR18## wherein X is an oxygen atom, the hydroxyimino grouping >N--OH or two hydrogen atoms
- R.sup.1 is hydrogen or a methyl group,
- R.sup.2 is a hydroxy group, a C.sub.1 -C.sub.10 alkoxy or C.sub.1 -C.sub.10 alkanoyloxy group,
- R.sup.3 is hydrogen, 1-propinyl, 2-propenyl, the grouping --(CH.sub.2).sub.n CH.sub.2 Z, wherein
- n is 0, 1, 2, 3, 4 or 5,
- Z is hydrogen, cyano or the radical --OR.sup.5, wherein R.sup.5 is H C.sub.1 -C.sub.10 alkyl or C.sub.1 -C.sub.10 alkanoyl,
- the grouping --(CH.sub.2).sub.m C.tbd.C--Y, wherein
- m is 0, 1 or 2 and
- Y is hydrogen, fluorine, chlorine, bromine or iodine atom;
- or a C.sub.1 -C.sub.10 hydroxyalkyl, C.sub.1 -C.sub.10 alkoxyalkyl, or C.sub.1 -C.sub.10 alkanoyloxyalkyl radical,
- the grouping --(CH.sub.2).sub.p --CH.dbd.CH--(CH.sub.2).sub.k CH.sub.2 R.sup.6, wherein
- p is 0 or 1,
- k is 0, 1 or 2, and
- R.sup.6 means a hydrogen atom, a hydroxy group, a C.sub.1 -C.sub.4 alkoxy or C.sub.1 -C.sub.4 alkanoyloxy radical,
- or else R.sup.2 and R.sup.3 together stand for a radical of the formula ##STR19## wherein x=1 or 2, R.sup.4 is hydrogen;
- cyano;
- chlorine;
- fluorine;
- bromine;
- iodine;
- trialkylsilyl;
- trialkylstannyl;
- a straight-chain or branched, saturated or unsaturated C.sub.1-8 hydrocarbyl, C.sub.1-8 alkanoyl or C.sub.1-8 alkoxyalkyl radical;
- an amino group ##STR20## in which R.sup.7 and R.sup.8, each independently of one another, is hydrogen or a C.sub.1 -C.sub.4 alkyl group;
- a corresponding amine oxide ##STR21## a grouping --OR.sup.9 or --S(O).sub.i R.sup.9, wherein i is 0, 1 or 2,
- R.sup.9 means hydrogen, a methyl, ethyl, propyl, isopropyl, methoxyphenyl, allyl or a 2-dimethylaminoethyl group;
- a heteroaryl radical for the formula I.alpha. ##STR22## wherein A is a nitrogen oxygen or sulfur atom, --B--D--E-- is the element sequence --C--C--C--, --N--C--C-- or --C--N--C--, and R.sup.10 is hydrogen;
- cyano;
- chlorine;
- fluorine;
- bromine;
- iodine;
- trialkylsilyl;
- trialkylstannyl;
- a straight-chain or branched, saturated or unsaturated C.sub.1-8 hydrocarbyl, C.sub.1-8 alkanoyl or C.sub.1-8 alkoxyalkyl radical;
- an amino group ##STR23## or the radical --OR.sup.9 or --S(O).sub.i R.sup.9, wherein R.sup.7, R.sup.8, R.sup.9 and i each independently has one of the meanings already indicated;
- a heteroaryl radical of formula I.beta. ##STR24## wherein A is a nitrogen atom,
- --B--D--E-- is the element sequence --C--C--C--, --N--C--C--, --C--N--C-- or --C--C--N--, and
- R.sup.10 has the meaning already indicated;
- or a phenyl radical of formula I.tau. ##STR25## wherein R.sup.10 has the meaning already indicated, or a pharmacologically compatible addition salt thereof.
36 more elements
A method of inducing abortion, comprising administering an effective amount of an 11.beta.-aryl-4-estrene of formula I having progesterone antagonist activity ##STR26## wherein X is an oxygen atom, the hydroxyimino grouping >N--OH or two hydrogen atoms
- R.sup.1 is hydrogen or a methyl group,
- R.sup.2 is a hydroxy group, a C.sub.1 -C.sub.10 alkoxy or C.sub.1 -C.sub.10 alkanoyloxy group,
- R.sup.3 is hydrogen, 1-propinyl, 2-propenyl, the grouping --(CH.sub.2).sub.n CH.sub.2 Z, wherein
- n is 0, 1, 2, 3, 4 or 5,
- Z is hydrogen, cyano or the radical --OR.sup.5, wherein R.sup.5 is H, C.sub.1 -C.sub.10 alkyl or C.sub.1 -C.sub.10 alkanoyl,
- the grouping --(CH.sub.2).sub.m C.tbd.C--Y, wherein
- m is 0, 1 or 2 and
- Y is hydrogen, fluorine, chlorine, bromine or iodine atom;
- or a C.sub.1 -C.sub.10 hydroxyalkyl, C.sub.1 -C.sub.10 alkoxyalkyl, or C.sub.1 -C.sub.10 alkanoyloxyalkyl radical,
- the grouping --(CH.sub.2).sub.p --CH.dbd.CH--(CH.sub.2).sub.k CH.sub.2 R.sup.6, wherein
- p is 0 or 1,
- k is 0, 1 or 2, and
- R.sup.6 means a hydrogen atom, a hydroxy group, a C.sub.1 -C.sub.4 alkoxy or C.sub.1 -C.sub.4 alkanoyloxy radical,
- or else R.sup.2 and R.sup.3 together stand for a radical of the formula ##STR27## wherein x=1 or 2, R.sup.4 is hydrogen;
- cyano;
- chlorine;
- fluorine;
- bromine;
- iodine;
- trialkylsilyl;
- trialkylstannyl;
- a straight-chain or branched, saturated or unsaturated C.sub.1-8 hydrocarbyl, C.sub.1-8 alkanoyl or C.sub.1-8 alkoxyalkyl radical;
- an amino group ##STR28## in which R.sup.7 and R.sup.8, each independently of one another is hydrogen or a C.sub.1 -C.sub.4 alkyl group;
- a corresponding amine oxide ##STR29## a grouping --OR.sup.9 or --S(O).sub.i R.sub.9, wherein is 0, 1 or 2,
- R.sup.9 means hydrogen, a methyl, ethyl, propyl, isopropyl, methoxyphenyl, allyl or a 2-dimethylaminoethyl group;
- a heteroaryl radical for the formula I.alpha. ##STR30## wherein A is a nitrogen, oxygen or sulfur atom --B--D--E-- is the element sequence --C--C--, --N--C--C-- or --C--N--C--, and
- R.sup.10 is hydrogen;
- cyano;
- chlorine;
- fluorine;
- bromine;
- iodine;
- trialkylsilyl;
- trialkylstannyl;
- a straight-chain or branched, saturated or unsaturated C.sub.1-8 hydrocarbyl, C.sub.1-8 alkanoyl or C.sub.1-8 alkoxyalkyl radical;
- an amino group ##STR31## or the radical --OR.sup.9 or --S(O).sub.i R.sup.9, wherein R.sup.7, R.sup.8, R.sup.9 and i each independently has one of the meanings already indicated;
- a heteroaryl radical of formula I.beta. ##STR32## wherein A is a nitrogen atom ----B--D--E-- is the element sequence --C--C--C--, --N--C--C--, --C--N--C-- or --C--C--N--, and
- R.sup.10 has the meaning already indicated;
- or a phenyl radical of formula I.tau. ##STR33## wherein R.sup.10 has the meaning already indicated, or a pharmacologically compatible addition salt thereof.
36 more elements
A method of post-coital birth control, comprising administering an effective amount of an 11.beta.-aryl-4-estrene of formula I having progesterone antagonist activity ##STR34## wherein X is an oxygen atom, the hydroxyimino grouping >N--OH or two hydrogen atoms,
- R.sup.1 is hydrogen or a methyl group,
- R.sup.2 is a hydroxy group, a C.sub.1 -C.sub.10 alkoxy or C.sub.1 -C.sub.10 alkanoyloxy group,
- R.sup.3 is hydrogen, 1-propinyl, 2-propenyl, the grouping --(CH.sub.2).sub.n CH.sub.2 Z, wherein
- n is 0, 1, 2, 3, 4 or 5,
- Z is hydrogen, cyano or the radical --OR.sup.5, wherein R.sup.5 is H, C.sub.1 -C.sub.10 alkyl or C.sub.1 -C.sub.10 alkanoyl,
- the grouping --(CH.sub.2).sub.m C.tbd.C--Y, wherein
- m is 0, 1 or 2 and
- Y is hydrogen, fluorine, chlorine, bromine or iodine atom;
- or a C.sub.1 -C.sub.10 hydroxyalkyl, C.sub.1 -C.sub.10 alkoxyalkyl, or C.sub.1 -C.sub.10 alkanoyloxyalkyl radical,
- the grouping --(CH.sub.2).sub.p --CH.dbd.CH--(CH.sub.2).sub.k CH.sub.2 R.sup.6, wherein
- p is 0 or 1,
- k is 0, 1 or 2, and
- R.sup.6 means a hydrogen atom, a hydroxy group, a C.sub.1 -C.sub.4 alkoxy or C.sub.1 -C.sub.4 alkanoyloxy radical,
- or else R.sup.2 and R.sup.3 together stand for a radical of the formula ##STR35## wherein x=1 or 2, R.sup.4 is hydrogen;
- cyano;
- chlorine;
- fluorine;
- bromine;
- iodine;
- trialkylsilyl;
- trialkylstannyl;
- a straight-chain or branched, saturated or unsaturated C.sub.1-8 hydrocarbyl, C.sub.1-8 alkanoyl or C.sub.1-8 alkoxyalkyl radical;
- an amino group ##STR36## in which R.sup.7 and R.sup.8, each independently of one another, is hydrogen or a C.sub.1 -C.sub.4 alkyl group;
- a corresponding amine oxide ##STR37## a grouping --OR.sup.9 or --S(O).sub.i R.sup.9, wherein i is 0, 1 or 2,
- R.sup.9 means hydrogen, a methyl, ethyl, propyl, isopropyl, methoxyphenyl, allyl or a 2-dimethylaminoethyl group;
- a heteroaryl radical for the formula I.alpha. ##STR38## wherein A is a nitrogen, oxygen or sulfur atom, --B--D--E-- is the element sequence --C--C--C--, --N--C--C-- or --C--N--C--, and
- R.sup.10 is hydrogen;
- cyano;
- chlorine;
- fluorine;
- bromine;
- iodine;
- trialkylsilyl;
- trialkylstannyl;
- a straight-chain or branched, saturated or unsaturated C.sub.1-8 hydrocarbyl, C.sub.1-8 alkanoyl or C.sub.1-8 alkoxyalkyl radical;
- an amino group ##STR39## or the radical --OR.sup.9 or --S(O).sub.i R.sup.9, wherein R.sup.7, R.sup.8, R.sup.9 and i each independently has one of the meanings already indicated;
- a heteroaryl radical of formula I.beta. ##STR40## wherein A is a nitrogen atom, --B--D--E-- is the element sequence --C--C--C--, --N--C--C--, --C--N--C-- or --C--C--N--, and
- R.sup.10 has the meaning already indicated;
- or a phenyl radical of formula I.tau. ##STR41## wherein R.sup.10 has the meaning already indicated, or a pharmacologically compatible addition salt thereof.
36 more elements
A method of treating endometriosis, comprising administering an effecting amount of an 11.beta.-aryl-4-estrene of formula I having progesterone antagonist activity ##STR42## wherein X is an oxygen atom, the hydroxyimino grouping >N.about.OH or two hydrogen atoms,
- R.sup.1 is hydrogen or a methyl group,
- R.sup.2 is a hydroxy group, a C.sub.1 -C.sub.10 alkanoyloxy group,
- R.sup.3 is hydrogen, 1-propinyl, 2-propenyl, the grouping --(CH.sub.2).sub.n CH.sub.2 Z, wherein
- n is 0, 1, 2, 3, 4 or 5,
- Z is hydrogen, cyano or the radical --OR.sup.5, wherein R.sup.5 is H, C.sub.1 -C.sub.10 alkyl or C.sub.1 -C.sub.10 alkanoyl, the grouping --(CH.sub.2).sub.m C.tbd.C--Y, wherein
- m is 0, 1 or 2 and
- Y is hydrogen, fluorine, chlorine, bromine or iodine atom;
- or a C.sub.1 -C.sub.10 hydroxyalkyl, C.sub.1 -C.sub.10 alkoxyalkyl, or C.sub.1 -C.sub.10 alkanoyloxyalkyl radical, the grouping --(CH.sub.2).sub.p --CH.dbd.CH--(CH.sub.2).sub.k CH.sub.2 R.sup.6, wherein
- p is 0 or 1,
- k is 0, 1 or 2, and
- R.sup.6 means a hydrogen atom, a hydroxy group, a C.sub.1 -C.sub.4 alkoxy or C.sub.1 -C.sub.4 alkanoyloxy radial,
- or else R.sup.2 and R.sup.3 together stand for a radical of the formula ##STR43## wherein x=1 or 2 R.sup.4 is hydrogen;
- cyano;
- chlorine;
- fluorine;
- bromine;
- iodine;
- trialkylsilyl;
- trialkylstannyl;
- a straight-chain or branched, saturated or unsaturated C.sub.1-8 hydrocarbyl, C.sub.1-8 alkanoyl or C.sub.1-8 alkoxyalkyl radical;
- an amino group ##STR44## in which R.sup.7 and R.sup.8, each independently of one another, is hydrogen or a C.sub.1 -C.sub.4 alkyl group;
- a corresponding amine oxide ##STR45## a grouping --OR.sup.9 or --S(O).sub.i R.sup.9, wherein i is 0, 1 or 2,
- R.sup.9 means hydrogen, a methyl, ethyl, propyl, isopropyl, methoxyphenyl, allyl or a 2-dimethylaminoethyl group;
- a heteroaryl radical for the formula I.alpha. ##STR46## wherein A is a nitrogen, oxygen or sulfur atom, --B--D--E-- is the element sequence --C--C--C--, --N--C--C-- or --C--N--C--, and
- R.sup.10 is hydrogen;
- cyano;
- chlorine;
- fluorine;
- bromine;
- iodine;
- trialkylsilyl;
- trialkylstannyl;
- a straight-chain or branched, saturated or unsaturated C.sub.1-8 hydrocarbyl, C.sub.1-8 alkanoyl or C.sub.1-8 alkoxyalkyl radical;
- an amino group ##STR47## or the radical --OR.sup.9 or --S(O).sub.i R.sup.9, wherein R.sup.7, R.sup.8, R.sup.9 and i each independently has one of the meanings already indicated;
- a heteroaryl radical of formula I.beta. ##STR48## wherein A is a nitrogen atom, --B--D--E-- is the element sequence --C--C--C--, --N--C--C--, --C--N--C-- or --C--C--N--, and
- R.sup.10 has the meaning already indicated;
- or a phenyl radical of formula I.tau. ##STR49## whereto R.sup.10 has the meaning already indicated, or a pharmacologically compatible addition salt thereof.
34 more elements
Dependencies are inferred from the claim text.