Derivatives of azaindazole or diazaindazole type for treating a cancer overexpressing Trk
AssigneePierre Fabre Medicament
InventorsAnna Kruczynski, Laurent Creancier, El Bachir Kaloun, Karim Bedjeguelal, Rémi Rabot
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Abstract
The present invention relates to a compound of following formula (I) or a pharmaceutically acceptable salt or solvate of same, a tautomer of same, or a stereoisomer or mixture of stereoisomers of same in any proportions, such as a mixture of enantiomers, notably a racemic mixture, as well as pharmaceutical composition comprising such a compound, for use in the treatment of a cancer associated with the overexpression of at least one Trk protein.
Claims25
A method for treating a cancer associated with the overexpression of at least one Trk protein comprising the administration to a person in need thereof of an effective dose of a compound of following general formula (I):
- or a pharmaceutically acceptable salt or solvate of same, a tautomer of same, or a stereoisomer or mixture of stereoisomers of same in any proportions,
- wherein:
- Y1 and Y4 each represent, independently of each other, a CH group or a nitrogen atom on the condition that at least one of Y1 and Y4 represent a nitrogen atom,
- Y2 represents a C—X—Ar group,
- Y3 represents a C—W group,
- Ar represents an aryl or heteroaryl group optionally substituted by one or more groups selected from a halogen atom, (C1-C6)alkyl, (C1-C6)haloalkyl, (C1-C6)haloalkoxy, (C1-C6)halothioalkoxy, CN, NO2, OR11, SR12, NR13R14, CO2R15, CONR16R17, SO2R18, SO2NR19R20, COR21, NR22COR23, NR24SO2R25, and R26NR27R28 and/or optionally fused to a heterocycle,
- X represents a divalent group selected from O, S, S(O), S(O)2, NR4, S(NR4), S(O)(NR4), S(O)2(NR4), NR4S, NR4S(O), NR4S(O)2, CH2, CH2S, CH2S(O), CH2S(O)2, SCH2, S(O)CH2, S(O)2CH2, CH2CH2, CH═CH, CH2O, OCH2, NR4CH2, and CH2NR4,
- W represents an R5, SR5, OR5 or NR5R6 group,
- U represents a CH2 or NH group, one or more hydrogen atoms which may be replaced by a (C1-C6)alkyl group,
- V represents C(O), C(S) or CH2,
- n represents 0 or 1,
- R1 represents a hydrogen atom, or an OR7 or NR7R8 group,
- R2 represents a hydrogen atom, an optionally substituted heterocycle, NO2, OR9 or NR9R10,
- R3, R4, R11 to R25 and R27 to R28 each represent, independently of each other, a hydrogen atom or a (C1-C6)alkyl group,
- R5 and R6 each represent, independently of each other, a hydrogen atom or a (C1-C6)alkyl, optionally substituted aryl or optionally substituted benzyl group,
- R7, R8, R9 and R10 each represent, independently of each other, a hydrogen atom or an optionally substituted (C1-C6)alkyl or (C3-C12)cycloalkyl group or an optionally substituted heterocycle, and
- R26 represents a (C1-C6)alkyl group.
Dependencies are inferred from the claim text.