Compounds for treatment of cancer
The present invention relates to novel compounds having anti-cancer activity, methods of making these compounds, and their use for treating cancer and drug-resistant tumors, e.g. melanoma, metastatic melanoma, drug resistant melanoma, prostate cancer and drug resistant prostate cancer.
1. A method of treating cervical cancer in a subject in need thereof comprising administering a therapeutically effective amount of a compound having the structure of formula XI:
wherein
X is a bond;
Q is NH;
A is substituted or unsubstituted single-, fused- or multiple-ring, (hetero)cyclic ring systems; substituted or unsubstituted, saturated or unsaturated N-heterocycles; substituted or unsubstituted, saturated or unsaturated S-heterocycles; substituted or unsubstituted, saturated or unsaturated O-heterocycles; substituted or unsubstituted, unsaturated cyclic hydrocarbons; or substituted or unsubstituted or saturated or unsaturated mixed heterocycles;
wherein the A ring is optionally substituted by 1-5 substituents independently selected from O-alkyl, O-haloalkyl, F, Cl, Br, I, CN, —CH 2 CN, NH 2 , hydroxyl, —OC(O)CF 3 , C 1 -C 5 linear or branched alkyl, haloalkyl, alkylamino, aminoalkyl, —OCH 2 Ph, —NHCO-alkyl, COOH, —C(OPh, C(O)O-alkyl, C(O)H, —C(O)NH 2 or NO 2 ,
or an isomer, pharmaceutically acceptable salt, pharmaceutical product, tautomer, hydrate, N-oxide, or combinations thereof.
2. The method of treating cervical cancer according to claim 1 , wherein the compound has a structure of formula XI(e):
wherein, R 4 and R 5 are independently hydrogen, O-alkyl, O-haloalkyl, F, Cl, Br, I, haloalkyl, CN, —CH 2 CN, NH 2 , hydroxyl, —OC(O)CF 3 , C 1 -C 5 linear or branched alkyl, alkylamino, aminoalkyl, —OCH 2 Ph, —NHCO-alkyl, COOH, —C(O)Ph, C(O)O-alkyl, C(O)H, —C(O)NH 2 or NO 2 ; and
n is an integer between 1-4.
3. The method of treating cervical cancer according to claim 1 , wherein the compound is compound 17ya represented by the structure:
or a pharmaceutically acceptable salt thereof.
4. The method of treating cervical cancer according to claim 1 , wherein the compound is administered in a pharmaceutical composition with a pharmaceutically acceptable carrier.
5. The method of treating cervical cancer according to claim 1 further comprising administering another cancer therapy.
6. A method of treating cervical cancer in a subject in need thereof comprising administering a therapeutically effective amount of a compound having the structure of formula XI:
wherein
X is a NH;
Q is NH or S;
A is substituted or unsubstituted single-, fused- or multiple-ring (hetero)cyclic ring systems;
substituted or unsubstituted, saturated or unsaturated N-heterocycles; substituted or unsubstituted, saturated or unsaturated S-heterocycles; substituted or unsubstituted, saturated or unsaturated O-heterocycles; substituted or unsubstituted, saturated or unsaturated cyclic hydrocarbons; or substituted or unsubstituted or saturated or unsaturated mixed heterocycles;
wherein the A ring is optionally substituted by 1-5 substituents which are independently O-alkyl, O-haloalkyl, F, Cl, Br, I, CN, —CH 2 CN, NH 2 , hydroxyl, —(CH 2 ) i NHCH 3 , —(CH 2 ) i NH 2 , —(CH 2 ) i N(CH 3 ) 2 , —OC(O)CF 3 , C 1 -C 5 linear or branched alkyl, haloalkyl, alkylamino, aminoalkyl, —OCH 2 Ph, —NHCO-alkyl, COOH, —C(O)Ph, C(O)O-alkyl, C(O)H, —C(O)NH 2 or NO 2 ; and
i is an integer between 0-5, or an isomer, pharmaceutically acceptable salt, pharmaceutical product, tautomer, hydrate, N-oxide, or combinations thereof.
7. The method of treating cervical cancer according to claim 6 , wherein the compound has a structure of formula VIII:
R 4 , R 5 and R 6 are independently hydrogen, O-alkyl, O-haloalkyl, F, Cl, Br, I, haloalkyl, CN, —CH 2 CN, NH 2 , hydroxyl, —(CH 2 ) i NHCH 3 , —(CH 2 ) i NH 2 , —(CH 2 ) i N(CH 3 ) 2 , —OC(O)CF 3 , C 1 -C 5 linear or branched alkyl, alkylamino, aminoalkyl, —OCH 2 Ph, —NHCO-alkyl, COOH, —C(O)Ph, C(O)O-alkyl, C(O)H, —C(O)NH 2 or NO 2 ;
Q is S or —NH;
i is an integer between 0-5; and
n is an integer between 1-3.
8. The method of treating cervical cancer according to claim 6 , wherein the compound has a structure of formula XI(b):
wherein R 4 and R 5 are independently hydrogen, O-alkyl, O-haloalkyl, F, Cl, Br, I, CN, —CH 2 CN, NH 2 , hydroxyl, —(CH 2 ) i NHCH 3 , —(CH 2 ) i NH 2 , —(CH 2 ) i N(CH 3 ) 2 , —OC(O)CF 3 , C 1 -C 5 linear or branched alkyl, alkylamino, aminoalkyl, —OCH 2 Ph, —NHCO-alkyl, COOH, —C(O)Ph, C(O)O-alkyl, C(O)H, —C(O)NH 2 or NO 2 ;
i is an integer from 0-5; and
n is an integer between 1-4.
9. The method of treating cervical cancer according to claim 6 , wherein the compound has the structure of formula XI(c):
wherein R 4 and R 5 are independently hydrogen, O-alkyl, O-haloalkyl, F, Cl, Br, I, CN, —CH 2 CN, NH 2 , hydroxyl, —(CH 2 ) i NHCH 3 , —(CH 2 ) i NH 2 , —(CH 2 ) i N(CH 3 ) 2 , —OC(O)CF 3 , C 1 -C 5 linear or branched alkyl, haloalkyl, alkylamino, aminoalkyl, —OCH 2 Ph, —NHCO-alkyl, COOH, —C(O)Ph, C(O)O-alkyl, C(O)H, —C(O)NH 2 or NO 2 ;
i is an integer from 0-5; and
n is an integer between 1-4.
10. The method of treating cervical cancer according to claim 6 , wherein the compound is compound 55, represented by the structure:
or a pharmaceutically acceptable salt thereof.
11. The method of treating cervical cancer according to claim 6 further comprising administering another cancer therapy.