US 5,892,069 AGranted

Estrogenic compounds as anti-mitotic agents

AssigneeChildren's Medical Center Corporation

InventorsRobert John D'Amato, Moses Judah Folkman

Life of this patent

Estimating the term…

Abstract

The application discloses methods of treating mammalian diseases characterized by abnormal cell mitosis by administering estradiol derivatives including those comprising colchicine or combretastatin A-4 structural motifs of the general formulae found below in a dosage sufficient to inhibit cell mitosis. The application discloses novel compounds used in the methods.

Claims3

Dependent claims

A compound of the formula:

##STR6## wherein:
I. R.sub.a --R.sub.o are defined as follows:
A) each R.sub.a, R.sub.b, R.sub.c, R.sub.d, R.sub.e, R.sub.f, R.sub.i, R.sub.j, R.sub.k, R.sub.L, R.sub.m, R.sub.o, independently is --R.sub.1, --OR.sub.1, --OCOR.sub.1, --SR.sub.1, --F, --NHR.sub.2, --Br, or --I;
and R.sub.g is --R.sub.1, --OR.sub.1, --OCOR.sub.1, --SR.sub.1, --F, --NHR.sub.2, --Br, --I, or --C.tbd.CH;
or
B) each R.sub.a, R.sub.b, R.sub.c, R.sub.f, R.sub.k, R.sub.L, R.sub.o, independently is --R.sub.1, --OR.sub.1, --OCOR.sub.1, --SR.sub.1, --F, --NHR.sub.2, --Br, or --I;
and each R.sub.d, R.sub.e, R.sub.i, R.sub.j, R.sub.m, independently is .dbd.O, --R.sub.1, --OR.sub.1, --OCOR.sub.1, --SR.sub.1, --F, NHR.sub.2, --Br or --I;
and R.sub.g is .dbd.O, --R.sub.1, --OR.sub.1, --OCOR.sub.1, --SR.sub.1, --F, --NHR.sub.2, --Br, --I, or --C.tbd.CH;
and
II. Z' is defined as follows:
A) Z' is X, where X is ##STR7## or B) Z' is ##STR8## where R.sub.n is --R.sub.1, --OR.sub.1, --SR.sub.1, --F, --NHR.sub.2, --Br or --I;
and X' is X, as defined above;
or X' is >C.dbd.O;
and
III. Z" is defined as follows:
A) Z" is Y, where Y is ##STR9## B) Z" is ##STR10## where Rp is --R.sub.1, OR.sub.1, --SR.sub.1, --F, --NHR.sub.2, --Br or --I and Y is defined as in III(A);
IV. provided that when each R.sub.b, R.sub.c, R.sub.k, R.sub.L, and R.sub.m is --H, and each R.sub.d, R.sub.e, and R.sub.j is --H.sub.2 ;
R.sub.f is --CH.sub.3 ;
R.sub.g is --OH;
or ##STR11## R.sub.i is --H, --OH, or .dbd.O;
R.sub.o is --H or --Br;
Z' is >COH;
and
Z" is >CH.sub.2 or >CHOH;
then
R.sub.a is not --F, --Br, --OH or --H;
and
V. provided that when each R.sub.b, R.sub.c, and R.sub.k, R.sub.L, is --H, and each R.sub.d, R.sub.e, R.sub.i, and R.sub.m is --H.sub.2 ;
R.sub.f is --CH.sub.3 ;
R.sub.g is --OH;
and
Z" is >CH.sub.2 ;
then
Z' is not >COCH.sub.3 ;
and
each R.sub.a, R.sub.o independently is not --OCH.sub.3 or --H;
and
VI. provided that when each R.sub.c, R.sub.k, R.sub.L, and R.sub.o is --H, and each R.sub.e, R.sub.j, and R.sub.m is --H.sub.2 ;
R.sub.a is --H or --OCH.sub.3,
R.sub.b is --H or --CH.sub.3,
R.sub.d is --OH;
R.sub.f is --CH.sub.3 ;
R.sub.g is .dbd.O;
R.sub.i is --OH, .dbd.O or --C.tbd.CH;
and
Z" is >CH.sub.2 ;
then
Z' is not >COH;
##STR12## or --H;
and VII. provided that when each R.sub.b, R.sub.c, R.sub.k, R.sub.L, and R.sub.o is --H, and each R.sub.d, R.sub.e, R.sub.i, R.sub.j, and R.sub.m is --H.sub.2 ;
R.sub.a is --OCH.sub.3 ;
R.sub.f is --CH.sub.3 ;
R.sub.g is --OH;
and
Z" is >CH.sub.2 ;
then
Z' is not >COH;
and
VIII. provided that when each R.sub.a, R.sub.b, R.sub.c, R.sub.k, R.sub.L, and R.sub.o is --H, and each R.sub.d, R.sub.e, R.sub.i, R.sub.j, and R.sub.m is --H.sub.2 ;
R.sub.f is --CH.sub.3 ;
R.sub.g is .dbd.O;
and
Z" is >CH.sub.2 ;
then
Z' is not >COH;
where, in each formula set forth above, each R.sub.1 and R.sub.2 independently is --H, or an alkyl, alkenyl or alkynl group of up to 6 carbons.

63 more elements

Dependencies are inferred from the claim text.

Facts

Application: 08/838,699Filed 25 Apr 1997 · division
Priority: 6 Aug 1993
Granted: 6 Apr 1999
Term ends: Not estimatedThe source records don’t support an estimate.

Classification35 codes

A61K 31/567
Not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol: substituted in position 17 alpha, e.g. mestranol, norethandrolone
A61K 31/27
Esters, e.g. nitroglycerine, selenocyanates: of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
A61K 31/56
Medicinal preparations containing organic active ingredients: compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives…
A61K 31/565
Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids: not substituted in position 17 beta by a…

Family

Serial102,767Parent of this continuation · filed 6 Aug 1993
Serial571,265Parent of this division · filed 12 Dec 1995
US 5,504,074 AParent of this continuation · filed 2 Apr 1996
US 5,661,143 AParent of this division
US 5,892,069 AThis patent

From the US filing history. Foreign family members aren’t listed.

Timeline

Citations

Open elsewhere

patentgrep

Loading patent…

Abstract

A compound of the formula:

##STR6## wherein:
I. R.sub.a --R.sub.o are defined as follows:
A) each R.sub.a, R.sub.b, R.sub.c, R.sub.d, R.sub.e, R.sub.f, R.sub.i, R.sub.j, R.sub.k, R.sub.L, R.sub.m, R.sub.o, independently is --R.sub.1, --OR.sub.1, --OCOR.sub.1, --SR.sub.1, --F, --NHR.sub.2, --Br, or --I;
and R.sub.g is --R.sub.1, --OR.sub.1, --OCOR.sub.1, --SR.sub.1, --F, --NHR.sub.2, --Br, --I, or --C.tbd.CH;
or
B) each R.sub.a, R.sub.b, R.sub.c, R.sub.f, R.sub.k, R.sub.L, R.sub.o, independently is --R.sub.1, --OR.sub.1, --OCOR.sub.1, --SR.sub.1, --F, --NHR.sub.2, --Br, or --I;
and each R.sub.d, R.sub.e, R.sub.i, R.sub.j, R.sub.m, independently is .dbd.O, --R.sub.1, --OR.sub.1, --OCOR.sub.1, --SR.sub.1, --F, NHR.sub.2, --Br or --I;
and R.sub.g is .dbd.O, --R.sub.1, --OR.sub.1, --OCOR.sub.1, --SR.sub.1, --F, --NHR.sub.2, --Br, --I, or --C.tbd.CH;
and
II. Z' is defined as follows:
A) Z' is X, where X is ##STR7## or B) Z' is ##STR8## where R.sub.n is --R.sub.1, --OR.sub.1, --SR.sub.1, --F, --NHR.sub.2, --Br or --I;
and X' is X, as defined above;
or X' is >C.dbd.O;
and
III. Z" is defined as follows:
A) Z" is Y, where Y is ##STR9## B) Z" is ##STR10## where Rp is --R.sub.1, OR.sub.1, --SR.sub.1, --F, --NHR.sub.2, --Br or --I and Y is defined as in III(A);
IV. provided that when each R.sub.b, R.sub.c, R.sub.k, R.sub.L, and R.sub.m is --H, and each R.sub.d, R.sub.e, and R.sub.j is --H.sub.2 ;
R.sub.f is --CH.sub.3 ;
R.sub.g is --OH;
or ##STR11## R.sub.i is --H, --OH, or .dbd.O;
R.sub.o is --H or --Br;
Z' is >COH;
and
Z" is >CH.sub.2 or >CHOH;
then
R.sub.a is not --F, --Br, --OH or --H;
and
V. provided that when each R.sub.b, R.sub.c, and R.sub.k, R.sub.L, is --H, and each R.sub.d, R.sub.e, R.sub.i, and R.sub.m is --H.sub.2 ;
R.sub.f is --CH.sub.3 ;
R.sub.g is --OH;
and
Z" is >CH.sub.2 ;
then
Z' is not >COCH.sub.3 ;
and
each R.sub.a, R.sub.o independently is not --OCH.sub.3 or --H;
and
VI. provided that when each R.sub.c, R.sub.k, R.sub.L, and R.sub.o is --H, and each R.sub.e, R.sub.j, and R.sub.m is --H.sub.2 ;
R.sub.a is --H or --OCH.sub.3,
R.sub.b is --H or --CH.sub.3,
R.sub.d is --OH;
R.sub.f is --CH.sub.3 ;
R.sub.g is .dbd.O;
R.sub.i is --OH, .dbd.O or --C.tbd.CH;
and
Z" is >CH.sub.2 ;
then
Z' is not >COH;
##STR12## or --H;
and VII. provided that when each R.sub.b, R.sub.c, R.sub.k, R.sub.L, and R.sub.o is --H, and each R.sub.d, R.sub.e, R.sub.i, R.sub.j, and R.sub.m is --H.sub.2 ;
R.sub.a is --OCH.sub.3 ;
R.sub.f is --CH.sub.3 ;
R.sub.g is --OH;
and
Z" is >CH.sub.2 ;
then
Z' is not >COH;
and
VIII. provided that when each R.sub.a, R.sub.b, R.sub.c, R.sub.k, R.sub.L, and R.sub.o is --H, and each R.sub.d, R.sub.e, R.sub.i, R.sub.j, and R.sub.m is --H.sub.2 ;
R.sub.f is --CH.sub.3 ;
R.sub.g is .dbd.O;
and
Z" is >CH.sub.2 ;
then
Z' is not >COH;
where, in each formula set forth above, each R.sub.1 and R.sub.2 independently is --H, or an alkyl, alkenyl or alkynl group of up to 6 carbons.

63 more elements

Facts

Application

08/838,699Filed 25 Apr 1997 · division

Priority

6 Aug 1993

Granted

6 Apr 1999

Term ends

Not estimatedThe source records don’t support an estimate.

Classification35 codes

A61K 31/567
Not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol: substituted in position 17 alpha, e.g. mestranol, norethandrolone
A61K 31/27
Esters, e.g. nitroglycerine, selenocyanates: of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
A61K 31/56
Medicinal preparations containing organic active ingredients: compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives…
A61K 31/565
Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids: not substituted in position 17 beta by a…

Family

Serial102,767Parent of this continuation · filed 6 Aug 1993

Serial571,265Parent of this division · filed 12 Dec 1995

US 5,504,074 AParent of this continuation · filed 2 Apr 1996

US 5,661,143 AParent of this division

US 5,892,069 AThis patent

From the US filing history. Foreign family members aren’t listed.