Compounds for treatment of cancer

Patent metadata

Field	Value
Publication number	US-9447049-B2
Application number	US-201213676650-A
Country	US
Kind code	B2
Filing date	Nov 14, 2012
Priority date	Mar 1, 2010
Publication date	Sep 20, 2016
Grant date	Sep 20, 2016

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 compound of the structure of formula XXV:

wherein
R 4 , R 5 and R 6 are independently hydrogen, O-alkyl, O-haloalkyl, F, Cl, Br, I, haloalkyl, CF 3 , 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 ;
R 9 and R 12 are independently hydrogen, linear or branched, substituted or unsubstituted C 1 -C 5 alkyl, or substituted or unsubstituted C 5 -C 6 cycloalkyl, substituted or unsubstituted aryl, —CH 2 Ph, substituted benzyl, haloalkyl, aminoalkyl, —OCH 2 Ph, substituted or unsubstituted SO 2 -aryl, substituted or unsubstituted —(C═O)-aryl or OH;
wherein the substitutions are independently selected from the group consisting of hydroxyl, aliphatic straight- or branched-chain C 1 to C 10 hydrocarbon, alkoxy, haloalkoxy, aryloxy, nitro, cyano, alkyl-CN, halo, haloalkyl, dihaloalkyl, trihaloalkyl, COOH, C(O)Ph, C(O)-alkyl, C(O)O-alkyl, C(O)H, C(O)NH 2 , —OC(O)CF 3 , —OCH 2 Ph, amino, aminoalkyl, alkylamino, mesylamino, dialkylamino, arylamino, amido, NHC(O)-alkyl, urea, alkyl-urea, alkylamido, haloalkylamido, arylamido, aryl, C 5 to C 7 cycloalkyl, arylalkyl, and combinations thereof;
i is an integer between 0-5; and
n is an integer between 1-3;
or its pharmaceutically acceptable salt, hydrate, polymorph, tautomer or stereoisomer.

2. The compound of claim 1 , wherein said compound is
(4-phenyl-1H-imidazol-2-yl)(3,4,5-trimethoxyphenyl)methanone (70a);
(4-(4-fluorophenyl)-1H-imidazol-2-yl)(3,4,5-trimethoxyphenyl)methanone (70b);
(4-(4-chlorophenyl)-1H-imidazol-2-yl)(3,4,5-trimethoxyphenyl)methanone (70c);
(4-(4-bromophenyl)-1H-imidazol-2-yl)(3,4,5-trimethoxyphenyl)methanone (70d);
(4-(4-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)(3,4,5-trimethoxyphenyl)methanone (70e);
(4-p-tolyl-1H-imidazol-2-yl)(3,4,5-trimethoxyphenyl)methanone (70f);
(4-(4-methoxyphenyl)-1H-imidazol-2-yl)(3,4,5-trimethoxyphenyl)methanone (70g);
(4-(4-(dimethylamino)phenyl)-1H-imidazol-2-yl)(3,4,5-trimethoxyphenyl)methanone (70h);
(4-(4-hydroxyphenyl)-1H-imidazol-2-yl)(3,4,5-trimethoxyphenyl)methanone (70i);
(5-methyl-4-phenyl-1H-imidazol-2-yl)(3,4,5-trimethoxyphenyl)methanone (70j);
(5-ethyl-4-phenyl-1H-imidazol-2-yl)(3,4,5-trimethoxyphenyl)methanone (70k);
(4-phenyl-5-propyl-1H-imidazol-2-yl)(3,4,5-trimethoxyphenyl)methanone (70l);
(1-methyl-4-phenyl-1H-imidazol-2-yl)(3,4,5-trimethoxyphenyl)methanone (70m);
(1-ethyl-4-phenyl-1H-imidazol-2-yl)(3,4,5-trimethoxyphenyl)methanone (70n);
(1-benzyl-4-phenyl-1H-imidazol-2-yl)(3,4,5-trimethoxyphenyl)methanone (70o); or
(1-cyclopentyl-4-phenyl-1H-imidazol-2-yl)(3,4,5-trimethoxyphenyl)methanone (70p).

3. A method of treating, suppressing, reducing the severity of, reducing the risk of, or inhibiting cancer comprising administering a compound according to claim 1 to a subject having cancer under conditions effective to treat the cancer.

4. A method of treating a drug resistant tumor or tumors comprising administering a compound according to claim 1 to a subject suffering from cancer under conditions effective to treat the drug resistant tumor or tumors.

5. The method of claim 3 , wherein said cancer is selected from the group consisting of prostate cancer, breast cancer, ovarian cancer, skin cancer, melanoma, lung cancer, colon cancer, leukemia, renal cancer, CNS cancer, and combinations thereof.

6. The method of claim 5 , wherein said cancer is metastatic cancer.

7. The method of claim 5 , wherein said administering is carried out in combination with another cancer therapy.

8. The method of claim 4 , wherein said tumor is melanoma cancer tumor.

9. The method of claim 4 , wherein said tumor is metastatic melanoma tumor.

10. The method of claim 4 , wherein said tumor is prostate cancer tumor.

11. The method of claim 4 , wherein said tumor is ovarian cancer tumor.

12. The method according to 4 , wherein said administering is carried out in combination with another cancer therapy.

13. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.

14. A method of destroying a cancerous cell comprising providing a compound according to claim 1 and contacting the cancerous cell with the compound under conditions effective to kill the cancer cell.

15. A pharmaceutical composition comprising a compound according to claim 2 and a pharmaceutically acceptable carrier.

16. A method of treating, suppressing, reducing the severity of, reducing the risk of, or inhibiting cancer comprising administering a compound according to claim 2 to a subject having cancer under conditions effective to treat the cancer.

17. A method of treating a drug resistant tumor or tumors comprising administering a compound according to claim 2 to a subject suffering from cancer under conditions effective to treat the drug resistant tumor or tumors.

18. A method of destroying a cancerous cell comprising providing a compound according to claim 2 and contacting the cancerous cell with the compound under conditions effective to kill the cancer cell.

Assignees

• Gtx Inc
• Univ Tennessee Res Found

Inventors

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

Classifications

• C07D417/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D233/64 Primary

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

• C07D277/24

  Radicals substituted by oxygen atoms · CPC title

• A61K31/4178

  not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin · CPC title

• C07D277/28

  Radicals substituted by nitrogen atoms · CPC title