Novel 1,2,3-Substituted Indolizine Derivatives, Inhibitors of FGFs, Method for Preparing Them and Pharmaceutical Compositions Containing Them

A method for the treatment of diseases requiring modulation of b-FGFs which comprises administering to a patient in need of such treatment a therapeutically effective amount of a compound of formula I,

• in which
• R1 represents a hydroxyl radical, a linear or branched alkoxy radical of 1 to 5 carbon atoms, a carboxyl radical, an alkoxycarbonyl radical of 2 to 6 carbon atoms or a radical of formula:
• —NR5R6
• —NH—SO2-Alk
• —NH—SO2-Ph
• —NH—CO-Ph
• —N(Alk)-CO-Ph
• —NH—CO—NH-Ph
• —NH—CO-Alk
• —NH—CO2-Alk
• —O—(CH2)n-cAlk
• —O-Alk-COOR7
• —O-Alk-O—R8
• —O-Alk-OH
• —O-Alk-C(NH2):NOH
• —O-Alk-NR5R6
• —O-Alk-CN
• —O—(CH2)n-Ph
• —O-Alk-CO—NR5R6
• —CO—NH—(CH2)m—COOR7
• —CO—NH-Alk
• in which
• Alk represents an alkyl radical or a linear or branched alkylene radical of 1 to 5 carbon atoms,
• cAlk represents a cycloalkyl radical of 3 to 6 carbon atoms,
• n represents an integer from 0 to 5,
• m represents an integer from 1 to 5,
• R5 and R6, which are identical or different, each represent a hydrogen atom, a linear or branched alkyl radical of 1 to 5 carbon atoms or a benzyl radical,
• R7 represents a hydrogen atom or an alkyl radical of 1 to 5 carbon atoms,
• R8 represents an alkyl radical of 1 to 5 carbon atoms or a radical —CO-Alk,
• Ph represents a phenyl radical which is optionally substituted with one or more halogen atoms, with one or more alkoxy radicals of 1 to 5 carbon atoms, with one or more carboxyl radicals or with one or more alkoxycarbonyl radicals of 2 to 6 carbon atoms,
• R2 represents a hydrogen atom, an alkyl radical of 1 to 5 carbon atoms, a haloalkyl radical of 1 to 5 carbon atoms containing 3 to 5 halogen atoms, a cycloalkyl radical of 3 to 6 carbon atoms or a phenyl radical which is optionally substituted with one or more halogen atoms, with one or more alkoxy radicals of 1 to 5 carbon atoms, with one or more carboxyl radicals or with one or more alkoxycarbonyl radicals of 2 to 6 carbon atoms,
• A represents a radical —CO—, —SO— or —SO2—,
• R3 and R4, which are identical or different, each represent a hydrogen atom, an alkoxy radical of 1 to 5 carbon atoms, an amino radical, a carboxyl radical, an alkoxycarbonyl radical of 2 to 6 carbon atoms, a hydroxyl radical, a nitro radical, a hydroxyamino radical, a radical of formula
• -Alk-COOR7
• —NR5R6
• —NH-Alk-COOR7
• —NH—COO-Alk
• —N(R11)—SO2-Alk-NR9R10
• —N(R11)—SO2-Alk
• —N(R11)-Alk-NR5R6
• —N(R11)—CO-Alk-NR9R10
• —N(R11)—CO-Alk
• —N(R11)—CO—CF3
• —NH-Alk-HetN
• —O-Alk-NR9R10
• —O-Alk-CO—NR5R6
• —O-Alk-HetN
• in which n, m, Alk, R5, R6 and R7 have the meaning given above for R1, and
• R9 and R10, which are identical or different, each represent a hydrogen atom or an alkyl radical of 1 to 5 carbon atoms,
• R11 represents a hydrogen atom or a radical -Alk-COOR12 where R12 represents a hydrogen atom, an alkyl radical of 1 to 5 carbon atoms or a benzyl radical,
• HetN represents a 5- or 6-membered heterocycle containing at least one nitrogen atom and optionally another heteroatom chosen from nitrogen and oxygen,
• or R3 and R4 form together a 5- to 6-membered unsaturated heterocycle, provided, however, that when R3 represents an alkoxy radical and R4 represents a radical —O-Alk-NR9R10 or a hydroxyl radical, R1 does not represent an alkoxy radical;
• or a pharmaceutically acceptable salt thereof.