Compounds useful for treating cancer

Patent metadata

Field	Value
Publication number	US-9969715-B2
Application number	US-201314432328-A
Country	US
Kind code	B2
Filing date	Sep 30, 2013
Priority date	Sep 28, 2012
Publication date	May 15, 2018
Grant date	May 15, 2018

Abstract

The present invention relates to a compound of formula (I):

wherein A and A′ independently represent a phenylene group or a pyridylene group; R 2 is a hydrogen atom or a (C 1 -C 4 )alkyl group; R 3 is a 2-pyridyl group, 3-pyridyl group, a 4-pyridyl group, a 2-pyrimidinyl group, a 4-pyrimidinyl group or a 5-pyrimidinyl group; R 4 is a carbonyl group or a sulfonyl group; and R 5 is a —NH—(CH 2 ) a —NR 6 R 7 group or a 4-methylpiperazinyl group, with a being an integer from 1 to 4, R 6 and R 7 representing independently a (C 1 -C 4 )alkyl group, or R 6 and R 7 together with the nitrogen atom to which they are linked forming a heterocycle group which is chosen among a 4-methylpiperazinyl group, a morpholino group, a pyrrolidinyl group and a piperidino group; or any one of its pharmaceutically acceptable salt.

First claim

The invention claimed is:

1. A compound of formula (I):

wherein
R 2 is a hydrogen atom or a (C 1 -C 4 )alkyl group;
R 3 is a 2-pyridyl group, 3-pyridyl group or a 4-pyridyl group;
R 4 is a carbonyl group or a sulfonyl group; and
R 5 is a —NH—(CH 2 ) a —NR 6 R 7 group, with a being an integer from 1 to 4, R 6 and R 7 representing independently a (C 1 -C 4 )alkyl group;
or any one of its pharmaceutically acceptable salt.

2. A compound of formula (I) according to claim 1
wherein
R 2 is a hydrogen atom or a methyl group;
R 3 is a 2-pyridyl or a 4-pyridyl group;
R 4 is a carbonyl group or a sulfonyl group; and
R 5 is a —NH—(CH 2 ) a —NR 6 R 7 group, with a being an integer from 2 to 3, R 6 and R 7 representing an ethyl group;
or any one of its pharmaceutically acceptable salt.

3. Compound of formula (I) according to claim 1 wherein the group —NH— between the two phenylene groups and the group —R 4 -R 5 are in position meta from each other.

4. A compound of formula (I) according to claim 1 , wherein R 4 is a carbonyl group and
R 2 is a hydrogen atom or a (C 1 -C 4 )alkyl group;
R 3 is a 2-pyridyl group, 3-pyridyl group or a 4-pyridyl group; and
R 5 is a —NH—(CH 2 ) a —NR 6 R 7 group, with a being an integer from 1 to 4, R 6 and R 7 representing independently a (C 1 -C 4 )alkyl group;
or any one of its pharmaceutically acceptable salt.

5. A compound of formula (I) according to claim 1 chosen among
(1) N-(3-(diethylamino)propyl)-3-((3-(pyridin-4-ylcarbamoyl)phenyl)amino) benzamide
(2) 3-((4-((3-(diethylamino)propyl)carbamoyl)phenyl)amino)-N-(pyridin-4-yl)benzamide
(5) 3-((3-(N-(3-(diethylamino)propyl)sulfamoyl)phenyl)amino)-N-(pyridin-4-yl)benzamide
(11) N-(3-(diethylamino)propyl)-3-((3-(pyridin-2-ylcarbamoyl)phenyl)amino) benzamide
(13) N-(3-(diethylamino)propyl)-3-((4-(pyridin-4-ylcarbamoyl)phenyl)amino) benzamide
(17) 3-((3-((3-(diethylamino)propyl)carbamoyl)phenyl)amino)-N-methyl-N-(pyridin-4-yl)benzamide
(19) 3-((3-(N-(3-(diethylamino)propyl)sulfamoyl)phenyl)amino)-N-methyl-N-(pyridin-4-yl)benzamide
and their pharmaceutically acceptable salts.

6. Process for the preparation of compounds of formula (I) according to claim 1 comprising reacting a compound of formula (II)

wherein R 2 and R 3 are as defined in claim 1 ,
with a compound of formula (III)

wherein X is a chlorine atom, an iodine atom or a bromine atom, and R 4 and R 5 are as defined in claim 1 , wherein the reaction takes place in a protic solvent, in presence of an inorganic base, in the presence of a diphosphine and of an organometallic catalyst, the temperature being increased from 80 to 120° C. under an inert gas.

7. A method of treating a patient, the method comprising administering to a patient a medicine comprising an effective amount of compound of formula (I) according to claim 1 to treat breast cancer and kidney cancer.

8. Pharmaceutical composition comprising at least one compound of formula (I) as defined in claim 1 and a pharmaceutically acceptable excipient.

Assignees

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

Inventors

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

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07D239/42

  One nitrogen atom (nitro radicals C07D239/30) · CPC title

• C07D401/12

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

• C07D213/75

  Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates · CPC title

• C07D401/14 Primary

  containing three or more hetero rings · CPC title