US 2005/0137170 A1 · Novel phosphorous containing steroid mimics

Abstract

The present invention discloses novel steroid mimics wherein a tri- or tetravalent phosphorous atom is isosterically substituted at any one of the seventeen positions occupied by the carbon atom in the steroidal skeleton, and wherein each adjacent position to the phosphorous is either unsubstituted or optionally substituted by nitrogen or an oxygen atom to satisfy the valency of said phosphorous atom. The invention is illustrated schematically below using both aromatic and non-aromatic steroids. Although the isosteric substitution phosphorous atom in the above structures 3-7 is indicated at 13, 14, and 17 positions, it is to be noted that the phosphorous can be substituted at any one of the seventeen positions in non-aromatic or eleven positions in aromatic steroids. The phosphorous atom may be trivalent or tetravalent, and may be radioactive or non-radioactive. The adjacent atoms, X, Y, or Z may be carbon, oxygen, or nitrogen. Other positions in the steroid mimics 3-8 may be optionally substituted alkyl, aryl, or other polar or non-polar functional groups to optimize biodistribution, receptor binding, and pharmacokinetic properties.

Claims32

Dependent claims

A compound of Formula 9,

wherein P is —P— or —P═O;
X is —O— or —NR4;
R1 to R3 are independently selected from the group consisting of hydrogen;
C1-C10 alkyl;
carboxyl;
C1-C10 hydroxyalkyl;
C1-C10 alkoxycarbonyl;
C5-C10 aryl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl;
and C5-C10 arylalkyl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, halo, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl;
and R4 is selected from the group consisting of hydrogen;
C1-C10 alkyl;
C1-C10 acyl;
C1-C10 hydroxyalkyl;
C5-C10 aryl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, halo, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl;
and C5-C10 arylalkyl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, halo, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl.

12 more elements

A compound of Formula 10,

wherein P is —P— or —P═O;
X is —O— or —NR4;
R2 and R3 are independently selected from the group consisting of hydrogen;
C1-C10 alkyl;
carboxyl;
C1-C10 hydroxyalkyl;
C1-C10 alkoxycarbonyl;
C5-C10 aryl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl;
and C5-C10 arylalkyl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, halo, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl;
and R4 is selected from the group consisting of hydrogen;
C1-C10 alkyl;
C1-C10 acyl;
C1-C10 hydroxyalkyl;
C5-C10 aryl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, halo, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl;
and C5-C10 arylalkyl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, halo, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl.

12 more elements

A compound of Formula 11,

wherein P is —P— or —P═O;
X is —O— or —NR4;
R1 and R2 are independently selected from the group consisting of hydrogen;
C1-C10 alkyl;
carboxyl;
C1-C10hydroxyalkyl;
C1-C10 alkoxycarbonyl;
C5-C10 aryl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl;
and C5-C10 arylalkyl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, halo, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl;
and R4 is selected from the group consisting of hydrogen;
C1-C10 alkyl;
C1-C10 acyl;
C1-C10 hydroxyalkyl;
C5-C10 aryl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, halo, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl;
and C5-C10 arylalkyl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, halo, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl.

12 more elements

A compound of Formula 12,

wherein P is —P— or —P═O;
X is —O— or —NR4;
R1 to R3 are independently selected from the group consisting of hydrogen;
C1-C10 alkyl;
carboxyl;
C1-C10 hydroxyalkyl;
C1-C10 alkoxycarbonyl;
C5-C10 aryl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl;
and C5-C10 arylalkyl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, halo, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl;
R4 is selected from the group consisting of hydrogen;
C1-C10 alkyl;
C1-C10 acyl;
C1-C10 hydroxyalkyl;
C5-C10 aryl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, halo, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl;
and C5-C10 arylalkyl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, halo, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl.

12 more elements

A method of performing a diagnostic or a therapeutic procedure comprising administering to an individual an effective amount of compound of Formula 9,

wherein P is —P— or —P═O;
X is —O— or —NR4;
R1 to R3 are independently selected from the group consisting of hydrogen;
C1-C10 alkyl;
carboxyl;
C1-C10 hydroxyalkyl;
C1-C10 alkoxycarbonyl;
C5-C10 aryl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl;
and C5-C10 arylalkyl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, halo, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl;
and R4 is selected from the group consisting of hydrogen;
C1-C10 alkyl;
C1-C10 acyl;
C1-C10 hydroxyalkyl;
C5-C10 aryl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, halo, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl;
and C5-C10 arylalkyl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, halo, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl.

12 more elements

A method of performing a diagnostic or a therapeutic procedure comprising administering to an individual an effective amount of compound of Formula 10,

wherein P is —P— or —P═O;
X is —O— or —NR4;
R2 and R3 are independently selected from the group consisting of hydrogen;
C1-C10 alkyl;
carboxyl;
C1-C10 hydroxyalkyl;
C1-C10 alkoxycarbonyl;
C5-C10 aryl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl;
and C5-C10 arylalkyl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, halo, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl;
and R4 is selected from the group consisting of hydrogen;
C1-C10 alkyl;
C1-C10 acyl;
C1-C10 hydroxyalkyl;
C5-C10 aryl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, halo, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl;
and C5-C10 arylalkyl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, halo, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl.

12 more elements

A method of performing a diagnostic or a therapeutic procedure comprising administering to an individual an effective amount of compound of Formula 11,

wherein P is —P— or —P═O;
X is —O— or —NR4;
R1 and R2 are independently selected from the group consisting of hydrogen;
C1-C10 alkyl;
carboxyl;
C1-C10 hydroxyalkyl;
C1-C10 alkoxycarbonyl;
C5-C10 aryl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl;
and C5-C10 arylalkyl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, halo, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl;
and R4 is selected from the group consisting of hydrogen;
C1-C10 alkyl;
C1-C10 acyl;
C1-C10 hydroxyalkyl;
C5-C10 aryl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, halo, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl;
and C5-C10 arylalkyl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, halo, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl.

12 more elements

A method of performing a diagnostic or a therapeutic procedure comprising administering to an individual an effective amount of compound of Formula 12,

wherein P is —P— or —P═O;
X is —O— or —NR4;
R4 to R3 are independently selected from the group consisting of hydrogen;
C1-C10 alkyl;
carboxyl;
C1-C10 hydroxyalkyl;
C1-C10 alkoxycarbonyl;
C5-C10 aryl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl;
and C5-C10 arylalkyl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, halo, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl;
R4 is selected from the group consisting of hydrogen;
C1-C10 alkyl;
C1-C10 acyl;
C1-C10 hydroxyalkyl;
C5-C10 aryl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, halo, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl;
and C5-C10 arylalkyl unsubstituted or substituted with C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, halo, trihaloalkyl, carboxyl, C1-C10 acyl, C1-C10 hydroxyalkyl, amino, C1-C10 alkylamino, C1-C10 dialkylamino, and C1-C10 alkoxycarbonyl.

12 more elements

Dependencies are inferred from the claim text.

Novel phosphorous containing steroid mimics

Life of this patent

Novel phosphorous containing steroid mimics

Life of this patent

Abstract

Claims32