Amino-phthalazinone derivatives active as kinase inhibitors, process for their preparation and pharmaceutical compositions containing them

An amino-phthalazinone derivative represented by formula (I)

• 15
• wherein
• Ra and Rb are, each independently, a hydrogen atom or a group, optionally further substituted, selected from straight or branched C1-C6 alkyl, C3-C6 cycloalkyl or cycloalkyl C1-C6 alkyl, aryl, aryl C1-C6 alkyl, 5 to 7 membered heterocyclyl or heterocyclyl C1-C6 alkyl with from 1 to 3 heteroatoms selected among nitrogen, oxygen or sulfur;
• or one of Ra or Rb is hydrogen or an optionally substituted straight or branched C1-C6 alkyl group, and the other is a group selected from —COR′, —CONHR′, —COOR′ or —SO2R′, wherein R′ is hydrogen or an optionally substituted group selected from alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, as set forth above;
• R1 is a group of formula —CHR4R5 wherein R4 and R5 are, each independently, hydrogen or an optionally substituted group selected from straight or branched C1-C6 alkyl, C3-C6 cycloalkyl or cycloalkyl C1-C6 alkyl, aryl, aryl C1-C6 alkyl, 5 to 7 membered heterocyclyl or heterocyclyl C1-C6 alkyl with from 1 to 3 heteroatoms selected among nitrogen, oxygen or sulfur;
• or R1 is a group of formula —NHR′, —NR′COR″, —NR′CONHR″ or —NR′SO2R″, wherein R′ has the above reported meanings other than hydrogen, and R″ is hydrogen or has the meanings set forth above for R′;
• R2 is a hydrogen atom or it is a group, optionally further substituted, selected from straight or branched C1-C6 alkyl, C3-C6 cycloalkyl or cycloalkyl C1-C6 alkyl, aryl, aryl C1-C6 alkyl, 5 to 7 membered heterocyclyl or heterocyclyl C1-C6 alkyl with from 1 to 3 heteroatoms selected among nitrogen, oxygen or sulfur;
• any R3, being placed in one or more of the free positions 5, 6 and 8 of the phthalazinone ring are, independently from each other, halogen, nitro, carboxy, cyano or a group optionally further substituted selected from straight or branched C1-C6 alkyl, C3-C6 cycloalkyl or cycloalkyl C1-C6 alkyl, aryl, aryl C1-C6 alkyl, 5 to 7 membered heterocyclyl or heterocyclyl C1-C6 alkyl with from 1 to 3 heteroatoms selected among nitrogen, oxygen or sulfur;
• or R3 is a group selected from —COR′, —CONHR′, —SO2R′, —NR′R″, —NR′COR″, —NR′CONHR′ or —NR′SO2R″, wherein R′ and R″ are, the same or different, hydrogen or a group as set forth above;
• m is 0 or an integer from 1 to 3;
• or a pharmaceutically acceptable salt thereof;
• the compounds N- [3,4-dihydro-4-oxo-1- (4-pyridinylmethyl) -6-phthalazinyl]-acetamide and N-[3,4-dihydro-4-oxo-1-(4-pyridinylmethyl)-6-phthalazinyl]-2,2,2-trifluoro-acetamide, being excluded.

A library of two or more amino-phthalazinone derivatives of formula (I)

• 24
• wherein
• Ra and Rb are, each independently, a hydrogen atom or a group, optionally further substituted, selected from straight or branched C1-C6 alkyl, C3-C6 cycloalkyl or cycloalkyl C1-C6 alkyl, aryl, aryl C1-C6 alkyl, 5 to 7 membered heterocyclyl or heterocyclyl C1-C6 alkyl with from 1 to 3 heteroatoms selected among nitrogen, oxygen or sulfur;
• or one of Ra or Rb is hydrogen or an optionally substituted straight or branched C1-C6 alkyl group, and the other is a group selected from —COR′, —CONHR′, —COOR′ or —SO2R′, wherein R′ is hydrogen or an optionally substituted group selected from alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, as set forth above;
• R1 is a group of formula —CHR4R5 wherein R4 and R5 are, each independently, hydrogen or an optionally substituted group selected from straight or branched C1-C6 alkyl, C3-C6 cycloalkyl or cycloalkyl C1-C6 alkyl, aryl, aryl C1-C6 alkyl, 5 to 7 membered heterocyclyl or heterocyclyl C1-C6 alkyl with from 1 to 3 heteroatoms selected among nitrogen, oxygen or sulfur;
• or R1 is a group of formula —NHR′, —NR′COR″, —NR′CONHR″ or —NR′SO2R″, wherein R′ has the above reported meanings other than hydrogen, and R″ is hydrogen or has the meanings set forth above for R′;
• R2 is a hydrogen atom or it is a group, optionally further substituted, selected from straight or branched C1-C6 alkyl, C3-C6 cycloalkyl or cycloalkyl C1-C6 alkyl, aryl, aryl C1-C6 alkyl, 5 to 7 membered heterocyclyl or heterocyclyl C1-C6 alkyl with from 1 to 3 heteroatoms selected among nitrogen, oxygen or sulfur;
• any R3, being placed in one or more of the free positions 5, 6 and 8 of the phthalazinone ring are, independently from each other, halogen, nitro, carboxy, cyano or a group optionally further substituted selected from straight or branched C1-C6 alkyl, C3-C6 cycloalkyl or cycloalkyl C1-C6 alkyl, aryl, aryl C1-C6 alkyl, 5 to 7 membered heterocyclyl or heterocyclyl C1-C6 alkyl with from 1 to 3 heteroatoms selected among nitrogen, oxygen or sulfur;
• or R3 is a group selected from —COR′, —CONHR′, —SO2R′, —NR′R″, —NR′COR″, —NR′CONHR′ or —NR′SO2R″, wherein R′ and R″ are, the same or different, hydrogen or a group as set forth above;
• m is 0 or an integer from 1 to 3;
• or a pharmaceutically acceptable salt thereof.