PRODRUGS OF FULVESTRANT
The present invention relates to Fulvestrant prodrugs and process for the preparation thereof. The present disclosure also relates to pharmaceutical composition of Fulvestrant prodrugs and method of treatment using the same.
1 . A compound of formula I:
wherein
R 1 is
wherein R 17 is selected from NH 2 , NHR 18 , or NR 19 R 20 ; R 18 is selected from group comprising optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 19 and R 20 are selected independently from group comprising optionally substituted alkyl, aryl, heteroaryl, heterocycloalkyl, cycloalkyl; or R 19 and R 20 are taken together along with the nitrogen to which they are attached to form a three to seven membered saturated, partially unsaturated or unsaturated heterocyclic ring and may optionally be substituted at a substitutable position with one or more R 21 radicals, wherein the one or more R 21 radicals are independently selected at each occurrence from the group consisting of optionally substituted alkyl, alkylcarbonyl, formyl, halo, haloalkyl, alkylphosphate, phosphate, oxo, cyano, nitro, amino, alkoxy, alkoxycarbonyl, carboxyalkyl, hydroxyalkyl, alkenyl, alkynyl, alkylthio, cycloalkyl, aryl, heteroaryl, aralkyl, heterocycloalkyl, alkylthioalkyl, arylcarbonyl, aralkylcarbonyl, alkoxyalkyl and;
R 2 is selected independently from group comprising of:
i)
wherein R 21 is selected from group comprising optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl; or —CR 22 R 23 ; where R 22 and R 23 are taken together along with the carbon to which they are attached to form a three to seven membered saturated, partially unsaturated or unsaturated heterocyclic ring in which up to 4 carbon atoms are replaced by heteroatoms chosen from the group consisting of O, S or N and may optionally be substituted at a substitutable position with one or more R 24 radicals, wherein one or more R 24 radicals are independently selected at each occurrence from the group consisting of optionally substituted alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkylcarbonyl, formyl, halo, alkylphosphate, phosphate, cyano, nitro, alkoxy, amino, alkoxycarbonyl, alkenyl, alkynyl, alkylthio and arylcarbonyl;
ii)
wherein each R 25 is selected independently from hydrogen; optionally substituted alkyl, aryl, or heteroaryl;
iii)
wherein each R 26 is selected independently from hydrogen; optionally substituted alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
iv) amino acids, wherein the amino acid is linked via ester linkage at the point of attachment;
enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates thereof.
2 . The compound of formula I according to claim 1 , wherein R 21 is selected from optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl; wherein one or more substitution is selected from group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkylamino, acyl, acyloxy, acylamino, aminocarbonyl, alkoxycarbonyl, alkoxyalkyloxy, alkoxycarbonyloxy, carbamate, sulfinyl, sulfonyl, alkoxy, sulfanyl, halogen, carboxy, trihalomethyl, cyano, hydroxy, mercapto, nitro, phosphate, alkylphosphate.
3 . The compound of formula II according to claim 1 :
wherein X is selected from O, C, N; and
Y is selected from optionally substituted aryl, heteroaryl, heterocycloalkyl, or cycloalkyl; and
R 3 is selected independently from group comprising of:
i)
wherein R 21 is selected from group comprising optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl; or —CR 22 R 23 ; where R 22 and R 23 are taken together along with the carbon to which they are attached to form a three to seven membered saturated, partially unsaturated or unsaturated heterocyclic ring in which up to 4 carbon atoms are replaced by heteroatoms chosen from the group consisting of O, S or N and may optionally be substituted at a substitutable position with one or more R 24 radicals, wherein one or more R 24 radicals are independently selected at each occurrence from the group consisting of optionally substituted alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkylcarbonyl, formyl, halo, alkylphosphate, phosphate, cyano, nitro, alkoxy, alkoxycarbonyl, alkenyl, alkynyl, alkylthio and arylcarbonyl;
ii)
wherein each R 25 is selected independently from hydrogen; optionally substituted alkyl, aryl, or heteroaryl;
iii)
wherein each R 26 is selected independently from hydrogen; optionally substituted alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
iv) amino acids, wherein the amino acid is linked via ester linkage at the point of attachment;
enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates thereof.
4 . The compound of formula II, according to claim 3 :
wherein X is selected from O, C, N; and
Y is selected from group comprising optionally substituted aryl, heteroaryl, heterocycloalkyl, or cycloalkyl; wherein the one or more substitution is selected from alkyl or alkoxy; and
R 3 is selected independently from group comprising of:
i)
wherein R 21 is optionally substituted alkyl; wherein one or more substitution is selected from amino, phosphate, alkylphosphate, or hydroxy;
ii)
wherein each R 25 is selected independently from group comprising of hydrogen; optionally substituted alkyl;
iii)
wherein each R 26 is selected independently from hydrogen; optionally substituted alkyl;
iv) amino acids; wherein the amino acid is linked via ester linkage at the point of attachment;
enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates thereof.
5 . The compound of formula III, according to claim 1 :
wherein R 5 is selected from hydrogen, alkyl;
R 6 is selected from group comprising optionally substituted alkyl, aryl, heteroaryl, heterocycloalkyl, or cycloalkyl; and
R 4 is selected independently from group comprising of:
i)
wherein R 21 is selected from group comprising optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl; or —CR 22 R 23 ; where R 22 and R 23 are taken together along with the carbon to which they are attached to form a three to seven membered saturated, partially unsaturated or unsaturated heterocyclic ring in which up to 4 carbon atoms are replaced by heteroatoms chosen from the group consisting of O, S or N and may optionally be substituted at a substitutable position with one or more R 24 radicals, wherein one or more R 24 radicals are independently selected at each occurrence from the group consisting of optionally substituted alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, hydroxy, alkylcarbonyl, formyl, halo, alkylphosphate, phosphate, cyano, nitro, alkoxy, amino, alkoxycarbonyl, alkenyl, alkynyl, alkylthio and arylcarbonyl;
ii)
wherein each R 25 is selected independently from hydrogen; optionally substituted alkyl, aryl, or heteroaryl;
iii)
wherein each R 26 is selected independently from hydrogen; optionally substituted alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
iv) amino acids, wherein the amino acid is linked via ester linkage at the point of attachment;
enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates thereof.
6 . The compound of formula III, according to claim 5 :
Wherein R 5 is selected from hydrogen, alkyl;
R 6 is selected from group comprising optionally substituted alkyl or aryl, wherein one or more substitution is selected from alkyl, alkoxy, halo, heteroaryl, heterocycloalkyl, cycloalkyl, amino, or hydroxy; and
R 4 is selected independently from group consisting of:
i)
wherein R 21 is optionally substituted alkyl; wherein one or more substitution is selected from amino, phosphate, alkylphosphate, or hydroxy;
ii)
wherein each R 25 is selected independently from hydrogen, or optionally substituted alkyl;
iii)
wherein each R 26 is selected independently from hydrogen or optionally substituted alkyl;
iv) amino acids, wherein the amino acid is linked via ester linkage at the point of attachment;
enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates thereof.
7 . The compound according to claim 1 , selected from group consisting of:
pharmaceutically acceptable salts or solvates thereof.
8 . A compound of formula IV:
wherein R 7 is
wherein each R 25 and R 26 is selected independently from hydrogen, optionally substituted alkyl, aryl or heteroaryl; and
R 8 is selected independently from group comprising of:
i)
wherein R 21 is selected from group comprising optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl; or —CR 22 R 23 ; where R 22 and R 23 are taken together along with the carbon to which they are attached to form a three to seven membered saturated, partially unsaturated or unsaturated heterocyclic ring in which up to 4 carbon atoms are replaced by heteroatoms chosen from the group consisting of O, S or N and may optionally be substituted at a substitutable position with one or more R 24 radicals, wherein one or more R 24 radicals are independently selected at each occurrence from the group consisting of optionally substituted alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkylcarbonyl, formyl, halo, alkylphosphate, phosphate, cyano, nitro, alkoxy, amino, alkoxycarbonyl, alkenyl, alkynyl, alkylthio and arylcarbonyl;
ii)
wherein R 17 is selected from NH 2 , NHR 18 or NR 19 R 20 ; R 18 is selected from group comprising optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 19 and R 20 are selected independently from group comprising optionally substituted alkyl, aryl, heteroaryl, heterocycloalkyl, cycloalkyl; or R 19 and R 20 are taken together along with the nitrogen to which they are attached to form a three to seven membered saturated, partially unsaturated or unsaturated heterocyclic ring and may optionally be substituted at a substitutable position with one or more R 21 radicals, wherein the one or more R 21 radicals are independently selected at each occurrence from the group consisting of optionally substituted alkyl, alkylcarbonyl, formyl, halo, haloalkyl, alkylphosphate, phosphate, oxo, cyano, nitro, amino, alkoxy, alkoxycarbonyl, —C(O)-aminoacid, carboxyl, carboxyalkyl, hydroxyalkyl, alkenyl, alkynyl, alkylthio, cycloalkyl, aryl, heteroaryl, aralkyl, heterocycloalkyl, alkylthioalkyl, arylcarbonyl, aralkylcarbonyl, alkoxyalkyl;
iii)
wherein R 27 is selected from group comprising optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
iv)
wherein R 28 is selected from group comprising optionally substituted alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein one or more substitution is selected from formyl, halo, phosphate, cyano, nitro, or amino;
v) amino acid, wherein the amino acid is linked via ester linkage at the point of attachment;
enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates thereof.
9 . The compound of formula IV according to claim 8 , wherein R 21 is selected from optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl; wherein one or more substitution is selected from group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkylamino, acyl, acyloxy, acylamino, aminocarbonyl, alkoxycarbonyl, alkoxyalkyloxy, alkoxycarbonyloxy, carbamate, sulfinyl, sulfonyl, alkoxy, sulfanyl, halogen, carboxy, trihalomethyl, cyano, hydroxy, mercapto, nitro, phosphate, alkylphosphate.
10 . The compound of formula V, according to claim 8 :
wherein W is selected from group comprising of hydrogen, or optionally substituted alkyl; and
R 9 is selected independently from group comprising of:
i)
wherein R 21 is selected from group comprising optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl; or —CR 22 R 23 ; where R 22 and R 23 are taken together along with the carbon to which they are attached to form a three to seven membered saturated, partially unsaturated or unsaturated heterocyclic ring in which up to 4 carbon atoms are replaced by heteroatoms chosen from the group consisting of O, S or N and may optionally be substituted at a substitutable position with one or more R 24 radicals, wherein one or more R 24 radicals are independently selected at each occurrence from the group consisting of optionally substituted alkyl, cycloalkyl, aryl, heteroaryl;
ii)
wherein R 17 is selected from NHR 18 , or NR 19 R 20 ; wherein R 18 is selected from group comprising optionally substituted alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl; R 19 and R 20 are taken together along with the nitrogen to which they are attached to form a three to seven membered saturated, partially unsaturated or unsaturated heterocyclic ring and may optionally be substituted at a substitutable position with one or more R 21 radicals, wherein the R 21 radicals are independently selected independently from the group consisting of optionally substituted alkyl, carboxyl, alkylcarbonyl, amino, —C(O)-aminoacid, cycloalkyl, aryl, aralkyl, heterocyclyoalkyl;
iii)
wherein R 27 is group comprising selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the substitution can be amino;
iv)
wherein R 28 is selected from group comprising optionally substituted alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein the substitution is amino;
v) amino acid, wherein the amino acid is linked via ester linkage at the point of attachment;
enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates thereof.
11 . The compound of formula V-A, according to claim 8 :
wherein W is selected from group comprising of hydrogen, or optionally substituted alkyl; and
R 9 is selected independently from group comprising of:
i)
wherein R 21 is selected from group comprising optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl; or —CR 22 R 23 ; where R 22 and R 23 are taken together along with the carbon to which they are attached to form a three to seven membered saturated, partially unsaturated or unsaturated heterocyclic ring in which up to 4 carbon atoms are replaced by heteroatoms chosen from the group consisting of O, S or N and may optionally be substituted at a substitutable position with one or more R 24 radicals, wherein one or more R 24 radicals are independently selected at each occurrence from the group consisting of optionally substituted alkyl, cycloalkyl, aryl, heteroaryl;
ii)
wherein R 17 is selected from NHR 18 , or NR 19 R 20 ; wherein R 18 is selected from group comprising optionally substituted alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl; R 19 and R 20 are taken together along with the nitrogen to which they are attached to form a three to seven membered saturated, partially unsaturated or unsaturated heterocyclic ring and may optionally be substituted at a substitutable position with one or more R 21 radicals, wherein the R 21 radicals are independently selected independently from the group consisting of optionally substituted alkyl, carboxyl, alkylcarbonyl, amino, —C(O)-aminoacid, cycloalkyl, aryl, aralkyl, heterocyclyoalkyl;
iii)
wherein R 27 is selected from group comprising optionally substituted alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein the substitution can be amino;
iv)
wherein R 28 is selected from group comprising optionally substituted alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein the substitution is amino;
v) amino acid, wherein the amino acid is linked via ester linkage at the point of attachment;
enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates thereof.
12 . The compound according to claim 8 , selected from group consisting of:
pharmaceutically acceptable salts or solvates thereof.
13 . A compound of formula VI:
wherein, R 10 is
wherein R 28 is selected from group comprising optionally substituted alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein one or more substitution is selected from formyl, halo, phosphate, cyano, nitro, amino, hydroxy, heterocycloalkyl, or alkoxy; and
R 11 is hydrogen or
where R 21 is selected from group comprising optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl; or —CR 22 R 23 ; where R 22 and R 23 are taken together along with the carbon to which they are attached to form a three to seven membered saturated, partially unsaturated or unsaturated heterocyclic ring in which up to 4 carbon atoms are replaced by heteroatoms chosen from the group consisting of O, S or N and may optionally be substituted at a substitutable position with one or more R 24 radicals, wherein one or more R 24 radicals are independently selected at each occurrence from the group consisting of optionally substituted alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkylcarbonyl, formyl, halo, alkylphosphate, phosphate, cyano, nitro, alkoxy, amino, alkoxycarbonyl, alkenyl, alkynyl, alkylthio, arylcarbonyl;
with the proviso that when R 11 is hydrogen, R 10 is not methyl or ethyl;
enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates thereof.
14 . The compound of formula (VI) according to claim 13 , R 21 is selected from optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl; wherein one or more substitution is selected from group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkylamino, acyl, acyloxy, acylamino, aminocarbonyl, alkoxycarbonyl, alkoxyalkyloxy, alkoxycarbonyloxy, carbamate, sulfinyl, sulfonyl, alkoxy, sulfanyl, halogen, carboxy, trihalomethyl, cyano, hydroxy, mercapto, nitro, phosphate, alkylphosphate.
15 . The compound of formula VII, according to claim 13 :
wherein, each Z 1 and Z 2 is independently selected from optionally substituted hydroxy, phosphate, or heterocycloalkyl; and
R 12 is hydrogen or
wherein R 21 is selected from group comprising optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl; or —CR 22 R 23 ; where R 22 and R 23 are taken together along with the carbon to which they are attached to form a three to seven membered saturated, partially unsaturated or unsaturated heterocyclic ring in which up to 4 carbon atoms are replaced by heteroatoms chosen from the group consisting of O, S or N and may optionally be substituted at a substitutable position with one or more R 24 radicals, wherein one or more R 24 radicals are independently selected at each occurrence from the group consisting of optionally substituted alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkylcarbonyl, formyl, halo, alkylphosphate, phosphate, cyano, nitro, alkoxy, alkoxycarbonyl, alkenyl, alkynyl, alkylthio, arylcarbonyl;
enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates thereof.
16 . The compound of formula VII, according to claim 13 :
wherein, each Z 1 and Z 2 is independently selected from optionally substituted hydroxy, phosphate, or heterocycloalkyl; and
R 12 is hydrogen or
wherein R 21 is selected from group comprising optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or heteroaryl; wherein one or more substitution is selected from alkyl, amino, or cycloalkyl;
enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates thereof.
17 . The compound according to claim 13 , selected from group consisting of:
pharmaceutically acceptable salts or solvates thereof.
18 . A compound of formula VIII:
wherein R 13 are selected from group comprising H; optionally substituted alkyl, aryl, heteroaryl, heterocycloalkyl, cycloalkyl; and R 14 are selected from group comprising optionally substituted alkyl, aryl, heteroaryl, heterocycloalkyl, cycloalkyl; or R 13 and R 14 are taken together along with the nitrogen to which they are attached to form a three to seven membered saturated, partially unsaturated or unsaturated heterocyclic ring and may optionally be substituted at a substitutable position with one or more R 21 radicals, wherein the one or more R 21 radicals are independently selected at each occurrence from the group consisting of optionally substituted alkyl, alkylcarbonyl, formyl, halo, haloalkyl, alkylphosphate, phosphate, phosphonyl, oxo, cyano, nitro, amino, alkoxy, alkoxycarbonyl, carboxyalkyl, hydroxyalkyl, alkenyl, alkynyl, alkylthio, cycloalkyl, aryl, heteroaryl, aralkyl, heterocycloalkyl, alkylthioalkyl, arylcarbonyl, aralkylcarbonyl, alkoxyalkyl;
enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates thereof.
19 . The compound of formula VIII, according to claim 18 :
wherein R 13 and R 14 are taken together along with the nitrogen to which they are attached to form a three to seven membered saturated, partially unsaturated or unsaturated heterocyclic ring and may optionally be substituted at a substitutable position with one or more R 21 radicals, wherein the one or more R 21 radicals are independently selected at each occurrence from the group consisting of substituted alkyl, alkylcarbonyl, formyl, halo, haloalkyl, alkylphosphate, phosphate, phosphonyl, oxo, cyano, nitro, amino, alkoxy, alkoxycarbonyl, carboxyalkyl, hydroxyalkyl, alkenyl, alkynyl, alkylthio, cycloalkyl, aryl, heteroaryl, aralkyl, heterocycloalkyl, alkylthioalkyl, arylcarbonyl, aralkylcarbonyl, alkoxyalkyl; enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates thereof; wherein one or more substitution on radical R 21 is selected from group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkylamino, acyl, acyloxy, acylamino, aminocarbonyl, alkoxycarbonyl, alkoxyalkyloxy, alkoxycarbonyloxy, carbamate, sulfinyl, sulfonyl, alkoxy, sulfanyl, halogen, carboxy, trihalomethyl, cyano, hydroxy, mercapto, nitro, phosphate, alkylphosphate.
20 . The compound of formula VIII, according to claim 18 :
wherein R 13 is selected from hydrogen, alkyl; and R 14 is selected from group comprising optionally substituted alkyl, heterocycloalkyl, or aryl; wherein one or more substitution is selected from alkyl, alkoxy, halo, heteroaryl, heterocycloalkyl, cycloalkyl, amino, or hydroxy;
enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates thereof.
21 . The compound according to claim 20 , selected from group consisting of:
pharmaceutically acceptable salts or solvates thereof.
22 . A compound of formula IX according to claim 18 ,
wherein S is selected from O, C, or N; and
T is selected from group comprising optionally substituted aryl, heteroaryl, heterocycloalkyl, cycloalkyl, amino,
wherein one or more substitution is selected from alkyl, alkoxy;
enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates thereof.
23 . The compound according to claim 22 , selected from group consisting of:
pharmaceutically acceptable salts or solvates thereof.
24 . A compound of formula X:
wherein, Q is selected from C or N; and
when Q is C, P 1 is selected independently from optionally substituted alkyl, optionally substituted
wherein substitution on
is alkyl; and P 2 and P 3 is selected independently from hydrogen or alkyl; and
when Q is N, P 2 is selected independently from optionally substituted alkyl, optionally substituted
wherein substitution on
is alkyl; P 1 is hydrogen and P 3 is optionally substituted alkyl;
enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates thereof.
25 . The compound according to claim 24 , selected from group consisting of:
pharmaceutically acceptable salts or solvates thereof.
26 . A compound of formula XI:
wherein R 15 and R 16 together forms a cyclic structure; wherein the said cyclic structure is selected from optionally substituted cycloalkyl, or heterocycloalkyl; wherein one or more substitution is selected from alkyl, alkoxy, halo, amino, or hydroxy; m and n can be independently 1 to 3;
enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates thereof.
27 . The compound according to claim 26 , selected from group consisting of:
pharmaceutically acceptable salts, or solvates thereof.
28 . The compound selected from group consisting of:
pharmaceutically acceptable salts or solvates thereof.
29 . A compound of formula
30 . A pharmaceutical composition comprising a compound selected from the group consisting of formula I, formula II, formula III, formula IV, formula V, formula VI, formula VII, formula VIII, formula IX, formula X and formula XI; enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates thereof; and a pharmaceutical acceptable excipient.
31 . A method of treating breast cancer comprising administration of a compound selected from group consisting of formula I, formula II, formula III, formula IV, formula V, formula V-A, formula VI, formula VII, formula VIII, formula IX, formula X, formula XI; enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates thereof.