Chemical molecules that inhibit the slicing mechanism for treating diseases resulting from splicing anomalies

Patent metadata

Field	Value
Publication number	US-10130595-B2
Application number	US-201514958602-A
Country	US
Kind code	B2
Filing date	Dec 3, 2015
Priority date	Jan 10, 2008
Publication date	Nov 20, 2018
Grant date	Nov 20, 2018

Abstract

A method of treating a disease selected from the group consisting of cancer, Duchenne muscular dystrophy, AIDS, and progeria, that includes administering to a patient in need thereof an effective quantity of at least one compound of formula (IV) or a pharmaceutically acceptable salt thereof.

First claim

What is claimed is:

1. A method of treating breast cancer, comprising:
administering to a patient in need thereof an effective quantity of at least one compound of formula (IV) or a pharmaceutically acceptable salt thereof:

where:
X 2 represents a nitrogen atom or a CR16 group;
R16 is a hydrogen atom or a group selected from:

X 1 represents:
a nitrogen atom,
a NR11 group, or
a CR10 group;

R10 represents:
a hydrogen atom,
an NR11R12, or
an OR11 group;

R11 and R12 independently represent a hydrogen atom or a C1 to C3 alkyl group;
R1 represents:
a hydrogen atom,
an NR11R12, or
an OR12 group,
with X1 representing a CH group when R1 represents an NR11R12 or an OR12 group;
A represents:

R4 represents:
a hydrogen atom,
a C1 to C3 alkyl group, or
a C(═O)NR14R15 group,
with R4 representing a hydrogen atom or a C1 to C3 alkyl group when R5 or R6 is not a hydrogen atom;

R5 represents:
a hydrogen atom,
a C(═O)NR14R15 group, or

with R5 representing a hydrogen atom when R4 or R6 is different than a hydrogen atom;

R6 represents:
a hydrogen atom,
a C(═O)NR14R15 group, or

group,
with R6 representing a hydrogen atom when R5 is not a hydrogen atom or when R4 is not a hydrogen atom or a C1 to C3 alkyl group;
R7 represents:
a hydrogen atom,
an NR11R12, or
an OR12 group,
with X2 representing a CH group when R7 represents an NR11R12 or an OR12 group;

R14 and R15 independently represent:
a hydrogen atom, or
a linear or branched, substituted or unsubstituted C1 to C10 alkyl group, wherein one or more carbon atoms can be substituted by a nitrogen atom; and

R21 and R22 independently represent a hydrogen atom or a methyl group.

2. The method of claim 1 , wherein at least one of R11 and R12 represents a methyl group or a trifluoromethyl group.

3. The method of claim 1 , wherein R1 represents an OR12 group.

4. The method of claim 3 , wherein R1 represents an OCH 3 group.

5. The method of claim 1 , wherein R4 represents a methyl group.

6. The method of claim 1 , wherein R6 represents a C(═O)NR14R15 group.

7. The method of claim 1 , wherein R7 is a hydrogen atom.

8. The method of claim 1 , wherein at least one of R21 and R22 represents a hydrogen atom.

9. The method of claim 1 , wherein at least one of R14 and R15 represents a linear or branched C1 to C10 alkyl group, wherein one or more carbon atoms can be substituted by a nitrogen atom, the alkyl group having at least one substituent selected from the group consisting of:
an —OH group,
a ═O group, and
the following groups, which may be substituted or unsubstituted:

10. The method of claim 1 , wherein at least one of R14 and R15 represents a linear or branched C1 to C10 alkyl group, wherein one or more carbon atoms can be substituted by a nitrogen atom, the alkyl group having at least one of the following substituents:

which are optionally substituted.

11. The method of claim 1 , wherein the compound of formula (IV) is selected from the group consisting of:
N-(3-Dimethylamino-propyl)-3-(4-trifluoromethoxy-phenylamino)-benzamide;
4-(4-Methoxy-phenylamino)-3-methyl-N-(3-methyl-butyl)-benzamide;
3-Methyl-N-(3-methyl-butyl)-4-(4-trifluoromethoxy-phenylamino)-benzamide;
N-(2-Dimethylamino-ethyl)-2-(4-trifluoromethoxy-phenylamino)-benzamide;
N-(2-Diethylamino-ethyl)-2-(4-trifluoromethoxyphenylamino)-benzamide;
N-(2-Diethylamino-propyl)-2-(4-trifluoromethoxy-phenylamino)-benzamide;
(N-Diethylamino)-{1-[4-(4-Methoxy-phenylamino)-phenyl]-1H-1,2,3-triazol-4-yl}-methylamine;
(N-Diethylamino)-{1-[4-(4-trifluoromethoxyphenylamino)-phenyl]-1H-1,2,3-triazol-4-yl}-methylamine;
(N-Diethylamino)-{1-[4-(4-N-dimethylamino-phenylamino)-phenyl]-1H-1,2,3-triazol-4-yl}-methylamine;
N-(3-Imidazol-1-yl-propyl)-2-(4-methoxy-phenylamino)-benzamide;
N-(3-Imidazol-1-yl-propyl)-2-(4-trifluoromethoxy-phenylamino)-benzamide;
2-(4-Dimethylamino-phenylamino)-N-(3-imidazol-1-yl-propyl)-benzamide;
N-(4-Diethylamino-1-methyl-butyl)-2-(4-dimethylaminophenylamino)-benzamide;
N-(2-Dimethylamino-ethyl)-4-(4-trifluoromethoxy-phenylamino)-benzamide;
N-(2-Dimethylamino-ethyl)-4-(4-dimethylamino-phenylamino)-benzamide;
N-(2-Dimethylamino-ethyl)-4-(4-methoxy-phenylamino)-3-methyl-benzamide;
N-(3-Diethylamino-propyl)-4-(4-methoxy-phenylamino)-benzamide;
N-(3-Diethylamino-propyl)-4-(4-methoxy-phenylamino)-3-methyl-benzamide;
N-(3-Diethylamino-propyl)-3-methyl-4-(4-trifluoromethoxy-phenylamino)-benzamide;
N-(3-Diethylamino-propyl)-4-(4-dimethylamino-phenylamino)-3-methyl-benzamide;
N-(2-Dimethylamino-ethyl)-3-methyl-4-(4-trifluoromethoxy-phenylamino)-benzamide;
3-{1-[4-(4-Methoxy-phenylamino)-phenyl]-1H-1,2,3-triazol-4-yl}-propan-1-ol;
(N-diethylamino)-{1-[3-(4-Methoxy-phenylamino)-phenyl]-1H-1,2,3-triazol-4-yl}-methylamine;
[4-(5-Chloro-1H-imidazol-2-yl)-2-methyl-phenyl]-(4-methoxy-phenyl)-amine;
N-(2-Diethylamino-ethyl)-4-(4-methoxy-phenylamino)-benzamide;
N-(2-Dimethylamino-ethyl)-2-(4-methoxy-phenylamino)-benzamide;
4-(4-Methoxy-phenylamino)-N-(3-methyl-butyl)-benzamide;
N-(3-Imidazol-1-yl-propyl)-4-(4-trifluoromethoxy-phenylamino)-benzamide;
[3-(4-Diethylaminomethyl-[1,2,3]triazol-1-yl)-phenyl]-(4-dimethylamino)-phenylamine;
N-(2-Diethylamino-ethyl)-2-(4-methoxy-phenylamino)-benzamide;
3-{1-[3-(4-Trifluoromethoxy-phenylamino)-phenyl]-1H-[1,2,3]triazol-4-yl}-propan-1-ol; and
3-{1-[3-(4-Dimethylamino-phenylamino)-phenyl]-1H-[1,2,3]triazol-4-yl}-propan-1-ol.

12. The method of claim 1 , wherein the compound of formula (IV) is selected from the group consisting of:
N-(2-Dimethylamino-ethyl)-4-(4-trifluoromethoxyphenylamino)-benzamide;
[4-(5-Chloro-1H-imidazol-2-yl)-2-methyl-phenyl]-(4-methoxy-phenyl)-amine; and
4-(4-Methoxy-phenylamino)-N-(3-methyl-butyl)-benzamide.

Assignees

• Centre Nationale De Recherche Scient
• Inst Curie
• Univ Montpellier

Inventors

• Tazi Jamal
• Grierson David
• Mahuteau-Betzer Florence
• Roux Pierre

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P7/12

  Antidiuretics, e.g. drugs for diabetes insipidus (ADH A61P5/10) · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P35/04

  specific for metastasis · CPC title