Compounds for treatment of cancer

Patent metadata

Field	Value
Publication number	US-11084811-B2
Application number	US-201916281291-A
Country	US
Kind code	B2
Filing date	Feb 21, 2019
Priority date	Mar 1, 2010
Publication date	Aug 10, 2021
Grant date	Aug 10, 2021

Abstract

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.

First claim

What is claimed:

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.

Assignees

• Oncternal Therapeutics Inc
• Univ Tennessee Res Found

Inventors

• Li Wei
• Xiao Min
• Dalton James
• Ahn Sunjoo
• Miller Duane D
• Wang Jin

Classifications

• C07D417/14 Primary

  containing three or more hetero rings · CPC title

• C07D233/64

  with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine · CPC title

• C07D213/76

  to which a second hetero atom is attached (nitro radicals C07D213/61) · CPC title

• C07D211/14

  with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom · CPC title

• C07D405/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title