Imidazo[1,2-b][1,2,4]triazol derivatives for use in therapy
The present invention relates to a compound of the formula (I) or a pharmaceutically acceptable salt thereof: wherein: R1 represents a hydrogen atom, a halogen atom, or a (C1 C4)hydroxyalkyl group, R2 represents a (C1-C6)alkyl group, and R3 represents a hydrogen atom, a (C1-C4)alkyl group or a halogen atom, and Ar represents a divalent aromatic ring or a (C5-C11) heteroarylene group. It further relates to the therapeutic uses thereof, in particular as anticancer agents.
1 . A compound of formula (I) or a pharmaceutically acceptable salt thereof:
wherein:
R1 represents a hydrogen atom, a halogen atom, or a (C 1 -C 4 ) hydroxyalkyl group,
R2 represents a (C 1 -C 6 )alkyl group,
R3 represents a hydrogen atom, a (C 1 -C 4 )alkyl group or a halogen atom, and
Ar represents a divalent aromatic ring or a (C 5 -C 11 ) heteroarylene group.
2 . The compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof,
wherein:
R1 is a halogen atom or a —CH 2 OH group,
R2 and R3 are as defined in claim 1 , and
Ar is a phenylene group or an indolylene group.
3 . The compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof,
wherein:
R2 is a methyl group, and
R3 is a hydrogen atom or a fluorine atom.
4 . The compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof, selected from one of the following compounds:
5 . A process for preparing the compound of formula (I) according to claim 1 , wherein a compound of formula (II)
wherein Ar, R2 and R3 are as defined in claim 1 is reacted with a catalyst.
6 . A process for preparing a compound of formula (II)
wherein a compound of formula (IV)
is reacted with an amine of the formula H 2 NR2,
wherein R2 represents a (C 1 -C 6 )alkyl group; R3 represents a hydrogen atom, a (C 1 -C 4 )alkyl group or a halogen atom; and Ar represents a divalent aromatic ring or a (C 5 -C 11 ) heteroarylene group.
7 . A compound selected from compounds of formula (IIa) or (IVa)
8 . A medicament, characterized in that it comprises the compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof.
9 . A pharmaceutical composition, characterized in that it comprises the compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.
10 . A method of preventing and/or treating autoimmune disorders, neurodegenerative diseases, cerebral traumas, psychiatric diseases, inflammatory diseases, and/or cancer, comprising administering to a subject in need thereof the compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof.
11 . The method according to claim 10 , wherein the cancer is a solid tumor.
12 . The compound of formula (I) according to claim 2 , wherein R1 is a flourine atom.
13 . The compound of formula (I) according to claim 4 , wherein the pharmaceutically acceptable salt is a trifluoroacetate salt.
14 . The process according to claim 5 , wherein the catalyst is a palladium catalyst.
15 . The process according to claim 5 , wherein the compound of formula (II) is reacted with:
palladium acetate in a solvent in the presence of 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl, or
tetrakis(triphenylphosphin) palladium (0), in acetonitrile and toluene, in the presence of a compound of formula (III)
wherein R1 represents a hydrogen atom, a halogen atom, or a (C 1 -C 4 ) hydroxyalkyl group.
16 . The process according to claim 15 , wherein the solvent is toluene.
17 . The process according to claim 6 , wherein the solvent is selected from toluene, benzene, or dichloromethane.
18 . The method according to claim 10 , wherein the cancer is selected from neuroblastoma, colorectal cancer, androgen-induced bladder cancer, lung cancer, hepatocellular carcinoma, breast cancer, esophageal cancer, or thyroid cancer.