US 2002/0119959 A1 · Estrogenic compounds as anti-mitotic agents

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.

Claims25

Dependent claims

A method for treating a mammalian disease characterized by abnormal cell mitosis, said method comprising administering to a mammal a cell-mitosis-inhibiting compound of the formula below, said compound being administered in an amount sufficient to inhibit cell mitosis:

1
wherein:
I. RaRo are defined as follows:
A) each Ra, Rb, Rc, Rd, Re, Rf, Ri, Rj, Rk, Rl, Rm, Ro, independently is —R1, —OR1, —OCOR1, —SR1 , —F, —NHR2, —Br, or —I;
and Rg is —R1, —OR1, —OCOR1, —SR1, —F, —NHR 2 , —Br, —I, or —C≡CH;
or
B) each Ra, Rb, Rc, Rf, Rk, R l Ro, independently is —R1, —OR1, —OCOR1, —SR1, —F, —NHR2, —Br, or —I;
and each Rd, Re, Ri, Rj, Rm, independently is ═O, —R1, —OR1, —OCOR1, —SR1, —F, —NHR2, —Br or —I;
and Rg is ═O, —R1, —OR1, —OCOR1, —SR1, —F, —NHR2, —Br, —I, or —C≡CH;
and
II. Z′ is defined as follows:
A) Z′ is X, where X is >COR1,
2
or
B) Z′ is
3
where Rnis —R1, —OR1, —SR1, —F, —NHR2, —Br or —I;
and X′ is X, as defined above;
or X′ is >C═O;
and
III. Z″ is defined as follows:
A) Z″ is Y, where Y is —O—,
4
>CHR1, >C═O,
5
where n is 0-6;
or
B) Z″ is
6
where RP is —R1,—OR1, —SR1, —F, —NHR2, —Br or —I;
and
IV. provided that when each Rb, Rc, Rd, Re, Ri, Rj, Rk, Rl , Rm and Ro is H;
Rf is —CH3;
Rg is —OH;
Z′ is >COH;
and
Z″ is >CH2;
then Ra is not —H;
where, in each formula set forth above, each R 1 and R 2 independently is —H, or substituted or unsubstituted alkyl, alkenyl or alkynl group of 1-6 carbons.

36 more elements

A compound of the general formula below, said compound being a cell-mitosis-inhibiting compound:

27
wherein:
I. Ra-Ro are defined as follows:
(A) each Ra, Rb, Rc, Rd, Re, Rf, Ri, Rj, Rk, Rl, Rm, Ro, independently is —R1, —OR1, —OCOR1, —SR1, —F, —NHR2,—Br, or —I;
and Rg is —R1, —OR1, —OCOR1, —SR1, —F, —NHR2, —Br, —I or —C≡CH;
or
(B) each Ra, Rb, Rc, Rf, Rk, Rl, Ro, is —R1, —OR1, —OCOR1, —SR1, —F, —NHR2, —Br, or —I;
and each Rd, Re, Ri, Rj, Rm, independently is ═O, —R1, —OR1, —OCOR1, —SR1, —F, —NHR2, —Br or •I;
and Rg is ═O, —R1, —OR1, —OCOR1, —SR1, —F, —NHR2, —Br, —I or —C≡CH;
and
II. Z′ is defined as follows:
A) Z′ is X, where X is >COR1,
28
or
B) Z′ is
29
where Rn is —R1, —OR1, —SR1, —F, —NHR2, —Br or —I;
or X′ is X, as defined above;
or X′ is >C═O;
and
III. Z″ is defined as follows:
A) Z″ is Y, where Y is —O—,
30
>CHR1, >C═O,
31
where n is 0-6;
or
B) Z″ is
32
where RP
is —R1, —OR1, —SR1, —F, —NHR2, —Br or —I;
provided that when:
3) each Rb, Rc, Rd, Re, RjRk, Rl, Rm, is —H;
Rf is —CH3;
Rg is —OH,
33
Ri is —H, —OH, or =O;
Ro is —H or —Br;
Z′ is >COH;
and
Z″ is >CH2 or —OH;
then
Ra is not —F, —Br, —OH or —H;
and
4) each Rb, Rc, Rd, Re, Ri, RjRk, Rl,
Rm, is —H;
Rf is —CH3;
Rg is —OH;
and
Z″ is >CH2;
then
Z′ is not >COCH3 or
34
and
each Ra, Ro independently or together are not —OCH3 or —H;
and
5) each Rc, Re, Rj, Rk, Rl, Rm, Ro is —H;
Ra is —H or —OCH3;
Rb is —H or —CH3;
Rd is —OH;
Rf is —CH3;
Rg is ═O;
Ri is —OH, ═O or —C≡CH;
and
Z″ is >CH2;
then
Z′ is not >COH;
35
or —H;
where, in each formula set forth above, each R1 and R2 independently is —H, or substituted or unsubstituted alkyl, alkenyl or alkynl group of 1-6 carbons.

67 more elements

Dependencies are inferred from the claim text.

Facts

Application

10/080,076Filed 21 Feb 2002

Priority

6 Aug 1993

Published

29 Aug 2002

Term ends

Not estimatedThe source records don’t support an estimate.

Classification15 codes

A61K 31/566
Not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol: having an oxo group in position 17, e.g. estrone
A61K 9/0019
Galenical forms characterised by the site of application: injectable compositions; Intramuscular, intravenous, arterial, subcutaneous…
A61K 9/0024
Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in…
A61K 31/21
Medicinal preparations containing organic active ingredients: esters, e.g. nitroglycerine, selenocyanates

Family

Application08/102,767Continuation · filed 6 Aug 1993

Application08/571,265Division · filed 12 Dec 1995

Application08/571,265Continuation · filed 12 Dec 1995

Application08/838,699Division · filed 25 Apr 1997

Application09/243,158Division · filed 2 Feb 1999

Application10/080,076Division · filed 21 Feb 2002

US 5,504,074 ARelated patent

US 5,661,143 ARelated patent

US 5,892,069 ARelated patent

US 6,528,676 B1Related patent

US 6,723,858 B2Related patent

US 2002/0119959 A1This patent

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

Abstract

Claims25

Dependent claims

1
wherein:
I. RaRo are defined as follows:
A) each Ra, Rb, Rc, Rd, Re, Rf, Ri, Rj, Rk, Rl, Rm, Ro, independently is —R1, —OR1, —OCOR1, —SR1 , —F, —NHR2, —Br, or —I;
and Rg is —R1, —OR1, —OCOR1, —SR1, —F, —NHR 2 , —Br, —I, or —C≡CH;
or
B) each Ra, Rb, Rc, Rf, Rk, R l Ro, independently is —R1, —OR1, —OCOR1, —SR1, —F, —NHR2, —Br, or —I;
and each Rd, Re, Ri, Rj, Rm, independently is ═O, —R1, —OR1, —OCOR1, —SR1, —F, —NHR2, —Br or —I;
and Rg is ═O, —R1, —OR1, —OCOR1, —SR1, —F, —NHR2, —Br, —I, or —C≡CH;
and
II. Z′ is defined as follows:
A) Z′ is X, where X is >COR1,
2
or
B) Z′ is
3
where Rnis —R1, —OR1, —SR1, —F, —NHR2, —Br or —I;
and X′ is X, as defined above;
or X′ is >C═O;
and
III. Z″ is defined as follows:
A) Z″ is Y, where Y is —O—,
4
>CHR1, >C═O,
5
where n is 0-6;
or
B) Z″ is
6
where RP is —R1,—OR1, —SR1, —F, —NHR2, —Br or —I;
and
IV. provided that when each Rb, Rc, Rd, Re, Ri, Rj, Rk, Rl , Rm and Ro is H;
Rf is —CH3;
Rg is —OH;
Z′ is >COH;
and
Z″ is >CH2;
then Ra is not —H;
where, in each formula set forth above, each R 1 and R 2 independently is —H, or substituted or unsubstituted alkyl, alkenyl or alkynl group of 1-6 carbons.

36 more elements

A compound of the general formula below, said compound being a cell-mitosis-inhibiting compound:

27
wherein:
I. Ra-Ro are defined as follows:
(A) each Ra, Rb, Rc, Rd, Re, Rf, Ri, Rj, Rk, Rl, Rm, Ro, independently is —R1, —OR1, —OCOR1, —SR1, —F, —NHR2,—Br, or —I;
and Rg is —R1, —OR1, —OCOR1, —SR1, —F, —NHR2, —Br, —I or —C≡CH;
or
(B) each Ra, Rb, Rc, Rf, Rk, Rl, Ro, is —R1, —OR1, —OCOR1, —SR1, —F, —NHR2, —Br, or —I;
and each Rd, Re, Ri, Rj, Rm, independently is ═O, —R1, —OR1, —OCOR1, —SR1, —F, —NHR2, —Br or •I;
and Rg is ═O, —R1, —OR1, —OCOR1, —SR1, —F, —NHR2, —Br, —I or —C≡CH;
and
II. Z′ is defined as follows:
A) Z′ is X, where X is >COR1,
28
or
B) Z′ is
29
where Rn is —R1, —OR1, —SR1, —F, —NHR2, —Br or —I;
or X′ is X, as defined above;
or X′ is >C═O;
and
III. Z″ is defined as follows:
A) Z″ is Y, where Y is —O—,
30
>CHR1, >C═O,
31
where n is 0-6;
or
B) Z″ is
32
where RP
is —R1, —OR1, —SR1, —F, —NHR2, —Br or —I;
provided that when:
3) each Rb, Rc, Rd, Re, RjRk, Rl, Rm, is —H;
Rf is —CH3;
Rg is —OH,
33
Ri is —H, —OH, or =O;
Ro is —H or —Br;
Z′ is >COH;
and
Z″ is >CH2 or —OH;
then
Ra is not —F, —Br, —OH or —H;
and
4) each Rb, Rc, Rd, Re, Ri, RjRk, Rl,
Rm, is —H;
Rf is —CH3;
Rg is —OH;
and
Z″ is >CH2;
then
Z′ is not >COCH3 or
34
and
each Ra, Ro independently or together are not —OCH3 or —H;
and
5) each Rc, Re, Rj, Rk, Rl, Rm, Ro is —H;
Ra is —H or —OCH3;
Rb is —H or —CH3;
Rd is —OH;
Rf is —CH3;
Rg is ═O;
Ri is —OH, ═O or —C≡CH;
and
Z″ is >CH2;
then
Z′ is not >COH;
35
or —H;
where, in each formula set forth above, each R1 and R2 independently is —H, or substituted or unsubstituted alkyl, alkenyl or alkynl group of 1-6 carbons.

67 more elements

Dependencies are inferred from the claim text.

Estrogenic compounds as anti-mitotic agents

Life of this patent

Abstract

Claims25

Estrogenic compounds as anti-mitotic agents

Life of this patent

Abstract

Claims25