Compounds for treating cancer

Patent metadata

Field	Value
Publication number	US-9637475-B2
Application number	US-201514789149-A
Country	US
Kind code	B2
Filing date	Jul 1, 2015
Priority date	Jun 12, 2009
Publication date	May 2, 2017
Grant date	May 2, 2017

Abstract

A method of preventing, inhibiting, or treating cancer that includes contacting a cell with at least one compound of formula (Ia) or a pharmaceutically acceptable salt thereof:

where:
R independently represents a hydrogen atom, a halogen atom, a (C 1 -C 3 )alkyl group, a —CN group, a hydroxyl group, a —COOR 1 group, a (C 1 -C 3 )fluoroalkyl group, a —NO 2 group, a —NR 1 R 2 group, or a (C 1 -C 3 )alkoxy group; R′ is a hydrogen atom, a halogen atom, a (C 1 -C 3 )alkyl group, a —NO 2 group, a (C 1 -C 3 )alkoxy group, or a —NR 1 R 2 group; and R 1 and R 2 are a hydrogen atom or a (C 1 -C 3 )alkyl group.

First claim

What is claimed is:

1. A compound having the following formula or a pharmaceutically acceptable salt thereof:

wherein:
R independently represent a hydrogen atom, a halogen atom, a —CN group, a hydroxyl group, a —COOR 1 group, a (C 1 -C 3 )fluoroalkyl group, a (C 1 -C 3 )fluoroalkoxy group, a —NO 2 group, a —NR 1 R 2 group, a (C 1 -C 4 )alkoxy group, a phenoxy group, or a (C 1 -C 3 )alkyl group optionally mono-substituted by a hydroxyl group,
R 1 and R 2 are independently a hydrogen atom or a (C 1 -C 3 )alkyl group,
n is 1, 2, or 3,
n′ is 1 or 2,
R′ is a hydrogen atom, a halogen atom, a (C 1 -C 3 )alkyl group, a hydroxyl group, a —COOR 1 group, a —NO 2 group, a —NR 1 R 2 group, a morpholinyl group, a morpholino group, a N-methylpiperazinyl group, a (C 1 -C 3 )fluoroalkyl group, a (C 1 -C 4 )alkoxy group, or a —CN group, and
R″ is a hydrogen atom or a (C 1 -C 4 )alkyl group, with the proviso that:
R′ and R are not simultaneously a hydrogen atom,
when R′ is a hydrogen atom, R is not a —NO 2 group or a —NH 2 group, and
when n is 2 and R′ is a hydrogen atom, R is not a COOC 2 H 5 group or a chlorine atom.

2. The compound of claim 1 , wherein R is a (C 1 -C 3 )fluoroalkoxy group.

3. The compound of claim 1 , wherein R′ is a —NR 1 R 2 group.

4. The compound of claim 1 , wherein R′ is a morpholinyl, a morpholino group, or a N-methylpiperazinyl group.

5. A compound selected from the group consisting of:
(143) 4-N,4-N-dimethyl-7-N[4-(trifluoromethoxy)phenyl]quinoline-4,7-diamine;
(144) 4-(morpholin-4-yl)-N-[4-(trifluoromethoxy)phenyl]quinolin-7-amine;
(166) N-(4-methoxyphenyl)-4-(4-methylpiperazin-1-yl)quinolin-7-amine;
(167) 4-methoxy-N[4-(trifluoromethoxy)phenyl]quinolin-7-amine; or
their pharmaceutically acceptable salts.

6. The compound of claim 5 , wherein the pharmaceutically acceptable salts are selected from hydrobromide, citrate, trifluoroacetate, ascorbate, hydrochloride, tartrate, triflate, maleate, mesylate, formate, acetate or fumarate.

7. A pharmaceutical composition comprising at least one compound as defined in claim 1 .

8. A pharmaceutical composition comprising at least one compound as defined in claim 2 .

9. A pharmaceutical composition comprising at least one compound as defined in claim 3 .

10. A pharmaceutical composition comprising at least one compound as defined in claim 4 .

11. A pharmaceutical composition comprising at least one compound as defined in claim 5 .

12. A pharmaceutical composition comprising at least one compound as defined in claim 6 .

13. The pharmaceutical composition according to claim 7 , further comprising a pharmaceutically acceptable support.

14. The pharmaceutical composition according to claim 8 , further comprising a pharmaceutically acceptable support.

15. The pharmaceutical composition according to claim 9 , further comprising a pharmaceutically acceptable support.

16. The pharmaceutical composition according to claim 10 , further comprising a pharmaceutically acceptable support.

17. The pharmaceutical composition according to claim 11 , further comprising a pharmaceutically acceptable support.

18. The pharmaceutical composition according to claim 12 , further comprising a pharmaceutically acceptable support.

19. A method of treating cancer selected from the group consisting of breast cancer, pancreatic cancer, prostate cancer, lung cancer, non-small cell lung cancer, thyroid cancer, liver cancer, and kidney cancer, comprising:
contacting a cell with at least one compound of formula (Iq) or a pharmaceutically acceptable salt thereof:

wherein:
R independently represent a hydrogen atom, a halogen atom, a —CN group, a hydroxyl group, a —COOR 1 group, a (C 1 -C 3 )fluoroalkyl group, a (C 1 -C 3 )fluoroalkoxy group, a —NO 2 group, a —NR 1 R 2 group, a (C 1 -C 4 )alkoxy group, a phenoxy group, or a (C 1 -C 3 )alkyl group optionally mono-substituted by a hydroxyl group,
R 1 and R 2 are independently a hydrogen atom or a (C 1 -C 3 )alkyl group,
n is 1, 2, or 3,
n′ is 1 or 2,
R′ is a hydrogen atom, a halogen atom, a (C 1 -C 3 )alkyl group, a hydroxyl group, a —COOR 1 group, a —NO 2 group, a —NR 1 R 2 group, a morpholinyl group, a morpholino group, a N-methylpiperazinyl group, a (C 1 -C 3 )fluoroalkyl group, a (C 1 -C 4 )alkoxy group, or a —CN group, and
R″ is a hydrogen atom or a (C 1 -C 4 )alkyl group.

20. The method of claim 19 , wherein:
R independently represent a hydrogen atom, a (C 1 -C 3 )alkoxy group, or a (C 1 -C 3 )fluoroalkoxy group, and
R′ is a hydrogen atom, a —NR 1 R 2 group, a N-methylpiperazinyl group, a (C 1 -C 3 )alkoxy group, or a morpholino group.

21. The method of claim 19 , wherein R is a (C 1 -C 3 )fluoroalkoxy group.

22. A method of treating cancer selected from the group consisting of breast cancer, pancreatic cancer, prostate cancer, lung cancer, non-small cell lung cancer, thyroid cancer, liver cancer, and kidney cancer comprising contacting a cell with at least one compound selected from the group consisting of:
(143) 4-N,4-N-dimethyl-7-N[4-(trifluoromethoxy)phenyl]quinoline-4,7-diamine;
(144) 4-(morpholin-4-yl)-N-[4-(trifluoromethoxy)phenyl]quinolin-7-amine;
(166) N-(4-methoxyphenyl)-4-(4-methylpiperazin-1-yl)quinolin-7-amine;
(167) 4-methoxy-N[4-(trifluoromethoxy)phenyl]quinolin-7-amine; or
pharmaceutically acceptable salts thereof.

23. The method of claim 22 , wherein the pharmaceutically acceptable salts are selected from hydrobromide, citrate, trifluoroacetate, ascorbate, hydrochloride, tartrate, triflate, maleate, mesylate, formate, acetate, or fumarate.

24. The method of claim 19 , further comprising a step of administering the compound to a patient in need of cancer treatment.

25. The method of claim 24 , wherein the compound is administered to the patient orally.

26. The method of claim 22 , further comprising a step of administering the compound to a patient in need of cancer treatment.

27. The method of claim 26 , wherein the compound is administered to the patient orally.

Assignees

• Abivax
• Centre Nat Rech Scient
• Inst Curie
• Univ Montpellier 2
• Univ Montpellier

Inventors

• Roux Pierre
• Mahuteau Florence
• Najman Romain
• Tazi Jamal
• Gadea Gilles
• Scherrer Didier
• Brock Carsten
• Cahuzac Nathalie

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07D215/60

  N-oxides · CPC title

• C07D403/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• A61K31/4709 Primary

  Non-condensed quinolines and containing further heterocyclic rings · CPC title

• C07D241/44

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring · CPC title