Imidazo[1,5-a]pyridine derivatives, method for preparing same and pharmaceutical compositions containing same
View Patent ↗The invention concerns compounds of formula I, a method for preparing said compounds, pharmaceutical compositions containing same and the therapeutic uses thereof.
1. A method of treating a patient for a disease requiring modulation of FGFs, said disease being atherosclerosis, comprising: administering to a patient in need thereof, an effective amount of a compound of formula I:
in which:
R, present on the 5, 6, 7 or 8 positions of the imidazo[1,5-a]pyridine, represents a hydrogen atom, a halogen atom, an alkyl radical of 1 to 5 carbon atoms, a hydroxyl radical, an alkoxy radical of 1 to 5 carbon atoms, a —COOR 6 radical or a radical of formula:
—NR 4 R 5
—NH—SO 2 -Alk
—NH—CO-Alk
—NR 6 —CO 2 -Alk
—O-Alk-COOR 6
—O-Alk-NR 4 R 5
—O—(CH 2 ) n -Ph
—CO—NR 4 R 5 , or
—CO—NH—CH(R 7 )—(CH 2 ) m —COOR 6
in which:
Alk represents an alkyl radical or an alkylene radical of 1 to 5 carbon atoms,
n represents an integer from 1 to 5,
m represents an integer from 0 to 4,
R 4 and R 5 represent, independently of one another, a hydrogen atom, an alkyl radical of 1 to 5 carbon atoms or a benzyl radical,
R 6 represents a hydrogen atom or an alkyl radical of 1 to 5 carbon atoms,
R 7 represents a hydrogen atom, an alkyl radical of 1 to 5 carbon atoms or a radical of formula:
-Alk-CONR 4 R 5
-Alk-OR 6
-Alk-NR 4 R 5
-Ph, or
—CH 2 Ph, and
Ph represents a phenyl radical optionally substituted by one or more groups chosen from halogen atoms, alkoxy radicals of 1 to 5 carbon atoms and —COOR 6 radicals where R 6 is as defined above;
R 1 represents a hydrogen atom, a halogen atom, a cyano radical, a —COOR 6 radical or a radical of formula:
—NR 4 R 5
—NH—SO 2 -Alk
—NH—CO—CF 3
—NH—CO-Ph
—NH—CO-Alk
—NH—CO 2 -Alk
—CONR 4 R 5
a phenyl radical optionally substituted by one or more groups chosen from halogen atoms, alkyl radicals of 1 to 5 carbon atoms, alkoxy radicals of 1 to 5 carbon atoms and —COOR 6 radicals,
a 5-membered heteroaryl radical comprising a heteroatom chosen from a sulfur atom, an oxygen atom or a nitrogen atom and optionally comprising a second nitrogen atom, said heteroaryl optionally being substituted by one or more groups chosen from halogen atoms, alkyl radicals of 1 to 5 carbon atoms, alkoxy radicals of 1 to 5 carbon atoms and —COOR 6 radicals, or
a 6-membered heteroaryl radical comprising 1 or 2 nitrogen atoms and optionally being substituted by one or more groups chosen from halogen atoms, alkyl radicals of 1 to 5 carbon atoms, alkoxy radicals of 1 to 5 carbon atoms and —COOR 6 radicals, in which Alk, Ph, R 4 , R 5 and R 6 are as defined as above;
R 2 and R 3 represent, independently of one another, a hydroxyl radical, an alkoxy radical of 1 to 5 carbon atoms, an amino radical, a —COOR 6 radical, a nitro radical or a radical of formula:
—NR 4 R 5
—NH—CO-Alk
—NH—CO-Ph
—NH—CO 2 -Alk
—NH—SO 2 -Alk
—CO—NR 4 R 5 , or
—CO—NHOH
in which Alk, Ph, R 4 , R 5 and R 6 are as defined as above;
or else R 2 and R 3 together form, with the carbon atoms of the phenyl ring to which they are attached, a 6-membered carbon ring comprising a nitrogen atom and oxygen atom,
or in the base or salt form.
2. A method of treating a patient for a cancer, comprising administering to a patient in need thereof, an effective amount of a compound of formula I:
in which:
R, present on the 5, 6, 7 or 8 positions of the imidazo[1,5-a]pyridine, represents a hydrogen atom, a halogen atom, an alkyl radical of 1 to 5 carbon atoms, a hydroxyl radical, an alkoxy radical of 1 to 5 carbon atoms, a —COOR 6 radical or a radical of formula:
—NR 4 R 5
—NH—SO 2 -Alk
—NH—CO-Alk
—NR 6 —CO 2 -Alk
—O-Alk-COOR 6
—O-Alk-NR 4 R 5
—O—(CH 2 ) n -Ph
—CO—NR 4 R 5 , or
—CO—NH—CH(R 7 )—(CH 2 ) m —COOR 6
in which:
Alk represents an alkyl radical or an alkylene radical of 1 to 5 carbon atoms,
n represents an integer from 1 to 5,
m represents an integer from 0 to 4,
R 4 and R 5 represent, independently of one another, a hydrogen atom, an alkyl radical of 1 to 5 carbon atoms or a benzyl radical,
R 6 represents a hydrogen atom or an alkyl radical of 1 to 5 carbon atoms,
R 7 represents a hydrogen atom, an alkyl radical of 1 to 5 carbon atoms or a radical of formula:
-Alk-CONR 4 R 5
-Alk-OR 6
-Alk-NR 4 R 5
-Ph, or
—CH 2 Ph, and
Ph represents a phenyl radical optionally substituted by one or more groups chosen from halogen atoms, alkoxy radicals of 1 to 5 carbon atoms and —COOR 6 radicals where R 6 is as defined above;
R 1 represents a hydrogen atom, a halogen atom, a cyano radical, a —COOR 6 radical or a radical of formula:
—NR 4 R 5
—NH—SO 2 -Alk
—NH—CO—CF 3
—NH—CO-Ph
—NH—CO-Alk
—NH—CO 2 -Alk
—CONR 4 R 5
a phenyl radical optionally substituted by one or more groups chosen from halogen atoms, alkyl radicals of 1 to 5 carbon atoms, alkoxy radicals of 1 to 5 carbon atoms and —COOR 6 radicals,
a 5-membered heteroaryl radical comprising a heteroatom chosen from a sulfur atom, an oxygen atom or a nitrogen atom and optionally comprising a second nitrogen atom, said heteroaryl optionally being substituted by one or more groups chosen from halogen atoms, alkyl radicals of 1 to 5 carbon atoms, alkoxy radicals of 1 to 5 carbon atoms and —COOR 6 radicals, or
a 6-membered heteroaryl radical comprising 1 or 2 nitrogen atoms and optionally being substituted by one or more groups chosen from halogen atoms, alkyl radicals of 1 to 5 carbon atoms, alkoxy radicals of 1 to 5 carbon atoms and —COOR 6 radicals,
in which Alk, Ph, R 4 , R 5 and R 6 are as defined as above;
R 2 and R 3 represent, independently of one another, a hydroxyl radical, an alkoxy radical of 1 to 5 carbon atoms, an amino radical, a —COOR 6 radical, a nitro radical or a radical of formula:
—NR 4 R 5
—NH—CO-Alk
—NH—CO-Ph
—NH—CO 2 -Alk
—NH—SO 2 -Alk
—CO—NR 4 R 5 , or
—CO—NHOH
in which Alk, Ph, R 4 , R 5 and R 6 are as defined as above;
or else R 2 and R 3 together form, with the carbon atoms of the phenyl ring to which they are attached, a 6-membered carbon ring comprising a nitrogen atom and oxygen atom,
or in the base or salt form, wherein the cancer is a carcinoma selected from: lung, breast, prostate and esophageal carcinomas, colon cancer, stomach cancer, melanomas, gliomas, lymphomas and leukemias.
3. The method of claim 2 , further comprising: administering the compound of formula I in combination with one or more anticancer active principle, optionally with radiotherapy.
4. A method of modulating FGFs, comprising administering to a solution containing same an effective amount of a compound of formula I
in which:
R, present on the 5, 6, 7 or 8 positions of the imidazo[1,5-a]pyridine, represents a hydrogen atom, a halogen atom, an alkyl radical of 1 to 5 carbon atoms, a hydroxyl radical, an alkoxy radical of 1 to 5 carbon atoms, a —COOR 6 radical or a radical of formula:
—NR 4 R 5
—NH—SO 2 -Alk
—NH—CO-Alk
—NR 6 —CO 2 -Alk
—O-Alk-COOR 6
—O-Alk-NR 4 R 5
—O—(CH 2 ) n -Ph
—CO—NR 4 R 5 , or
—CO—NH—CH(R 7 )—(CH 2 ) m —COOR 6
in which:
Alk represents an alkyl radical or an alkylene radical of 1 to 5 carbon atoms,
n represents an integer from 1 to 5,
m represents an integer from 0 to 4,
R 4 and R 5 represent, independently of one another, a hydrogen atom, an alkyl radical of 1 to 5 carbon atoms or a benzyl radical,
R 6 represents a hydrogen atom or an alkyl radical of 1 to 5 carbon atoms,
R 7 represents a hydrogen atom, an alkyl radical of 1 to 5 carbon atoms or a radical of formula:
-Alk-CONR 4 R 5
-Alk-OR 6
-Alk-NR 4 R 5
-Ph, or
—CH 2 Ph, and
Ph represents a phenyl radical optionally substituted by one or more groups chosen from halogen atoms, alkoxy radicals of 1 to 5 carbon atoms and —COOR 6 radicals where R 6 is as defined above;
R 1 represents a hydrogen atom, a halogen atom, a cyano radical, a —COOR 6 radical or a radical of formula:
—NR 4 R 5
—NH—SO 2 -Alk
—NH—CO—CF 3
—NH—CO-Ph
—NH—CO-Alk
—NH—CO 2 -Alk
—CONR 4 R 5
a phenyl radical optionally substituted by one or more groups chosen from halogen atoms, alkyl radicals of 1 to 5 carbon atoms, alkoxy radicals of 1 to 5 carbon atoms and —COOR 6 radicals,
a 5-membered heteroaryl radical comprising a heteroatom chosen from a sulfur atom, an oxygen atom or a nitrogen atom and optionally comprising a second nitrogen atom, said heteroaryl optionally being substituted by one or more groups chosen from halogen atoms, alkyl radicals of 1 to 5 carbon atoms, alkoxy radicals of 1 to 5 carbon atoms and —COOR 6 radicals, or
a 6-membered heteroaryl radical comprising 1 or 2 nitrogen atoms and optionally being substituted by one or more groups chosen from halogen atoms, alkyl radicals of 1 to 5 carbon atoms, alkoxy radicals of 1 to 5 carbon atoms and —COOR 6 radicals,
in which Alk, Ph, R 4 , R 5 and R 6 are as defined as above;
R 2 and R 3 represent, independently of one another, a hydroxyl radical, an alkoxy radical of 1 to 5 carbon atoms, an amino radical, a —COOR 6 radical, a nitro radical or a radical of formula:
—NR 4 R 5
—NH—CO-Alk
—NH—CO-Ph
—NH—CO 2 -Alk
—NH—SO 2 -Alk
—CO—NR 4 R 5 , or
—CO—NHOH
in which Alk, Ph, R 4 , R 5 and R 6 are as defined as above;
or else R 2 and R 3 together form, with the carbon atoms of the phenyl ring to which they are attached, a 6-membered carbon ring comprising a nitrogen atom and oxygen atom,
or in the base or salt form.