Claims for Patent: 8,299,057

Summary for Patent: 8,299,057

Title:	Substituted indazole derivatives active as kinase inhibitors
Abstract:	Substituted indazole derivatives of formula (I) and pharmaceutically acceptable salts thereof, as defined in the specification, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful in therapy in the treatment of diseases associated with a deregulated protein kinase activity, like cancer.
Inventor(s):	Lombardi Borgia; Andrea (Paullo, IT), Menichincheri; Maria (Milan, IT), Orsini; Paolo (Legnano, IT), Panzeri; Achille (Merate, IT), Perrone; Ettore (Boffalora Sopra Ticino, IT), Vanotti; Ermes (Milan, IT), Nesi; Marcella (Saronno, IT), Marchionni; Chiara (Milan, IT)
Assignee:	Nerviano Medical Sciences S.R.L. (Nerviano (MI), IT)
Application Number:	12/668,745
Patent Claims:	1. A compound of formula (I): ##STR00132## wherein: X is --CH.sub.2--, --CH(OH)--, --CH(OR')-- or --C(R'R'')--, wherein: R' is C.sub.1-C.sub.6 alkyl and R'' is hydrogen; Ar is phenyl, pyrazolyl or pyridyl optionally substituted with one or more substituents independently selected from halogen, nitro, COR4, OR7, NR5R6, NHSO.sub.2R10, a straight or branched C.sub.1-C.sub.6 alkyl optionally substituted by a heterocyclyl, in its turn optionally substituted by a straight or branched C.sub.1-C.sub.6 alkyl or an heterocyclylalkyl, or a heterocyclyl optionally substituted by a straight or branched C.sub.1-C.sub.6 alkyl, in its turn optionally substituted by a heterocyclyl or a C.sub.1-C.sub.6 alkoxycarbonyl, or a C.sub.1-C.sub.6 dialkylamino: R4 is NR5R6, or a heterocyclyl, optionally further substituted by a straight or branched C.sub.1-C.sub.6 alkyl, heterocyclylalkyl, heterocyclyl or a C.sub.1-C.sub.6 dialkylamino; R5 and R6 are independently hydrogen, R8R9N--C.sub.2-C.sub.6 alkyl, R8O--C.sub.2-C.sub.6 alkyl, a straight or branched C.sub.1-C.sub.6 alkyl optionally further substituted by C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 dialkylamino, halogen, phenyl, hydroxyl or heterocyclyl in its turn optionally substituted by alkyl, C.sub.3-C.sub.6 cycloalkyl optionally substituted by hydroxyl or trifluoro C.sub.1-C.sub.6 alkyl, heterocyclyl optionally substituted by C.sub.1-C.sub.6 alkyl in its turn optionally substituted by halogen or heterocyclyl, C.sub.1-C.sub.6 alkoxycarbonyl, C.sub.1-C.sub.6 dialkylamino, heterocyclyl, or phenyl, or R5 and R6, taken together with the nitrogen atom to which they are bonded, may form a heterocyclyl group optionally substituted by a straight or branched C.sub.1-C.sub.6 alkyl, in its turn optionally substituted by a heterocyclyl or a C.sub.1-C.sub.6 alkoxycarbonyl, a C.sub.1-C.sub.6 dialkylamino or a heterocyclyl; R7 is straight or branched C.sub.1-C.sub.6 alkyl, optionally substituted by C.sub.1-C.sub.6 dialkylamino or heterocyclyl in its turn substituted by C.sub.1-C.sub.6 alkyl; R8 and R9 are independently an optionally further substituted straight or branched C.sub.1-C.sub.6 alkyl; R10 is an optionally further substituted straight or branched C.sub.1-C.sub.6 alkyl; R is phenyl or pyridyl optionally substituted halogen or straight or branched C.sub.1-C.sub.6 alkyl; R1, R2 and R3 are hydrogen; or optical isomers, tautomers or pharmaceutically acceptable salt thereof. 2. A compound of formula (I) as defined in claim 1 wherein: X is --CH.sub.2--, --CH(OH)--, --CH(OR')-- or --C(R'R'')--, wherein R' is C.sub.1-C.sub.3 alkyl and R'' is hydrogen. 3. A compound of formula (I) as defined in claim 1 wherein: X is --CH.sub.2--, --CH(OH)--, --CH(OR')-- or --C(R'R'')--, where R' is methyl and R'' is hydrogen. 4. A compound of formula (I) as defined in claim 1, wherein Ar is a group of formula: ##STR00133## wherein Ra, Rb and Rc are independently hydrogen, halogen, nitro, COR4, NR5R6, OR7, NHSO.sub.2R10, R8R9N--C.sub.2-C.sub.6 alkyl, R8O--C.sub.2-C.sub.6 alkyl, a straight or branched C.sub.1-C.sub.6 alkyl optionally substituted by a heterocyclyl, in its turn optionally substituted by a straight or branched C.sub.1-C.sub.6 alkyl or a heterocyclylalkyl, or a heterocyclyl optionally substituted by a straight or branched C.sub.1-C.sub.6 alkyl, in its turn optionally substituted by a heterocyclyl or a C.sub.1-C.sub.6 alkoxycarbonyl, or a C.sub.1-C.sub.6 dialkylamino; wherein R4, R5, R6, R7, R8, R9 and R10 are as defined in claim 1 and R is a phenyl optionally substituted by halogen or straight or branched C.sub.1-C.sub.6 alkyl. 5. A compound of formula (I) as defined in claim 1, wherein Ar is a group of formula: ##STR00134## wherein Ra is hydrogen, halogen, nitro or NR5R6 and Rb is hydrogen, nitro, NR5R6, OR7 or R8R9N--C.sub.1-C.sub.6 wherein R4, R5, R6, R7, R8 and R9 are defined as in claim 1. 6. A compound, or a pharmaceutically acceptable salt thereof, selected from the group consisting of: N-(5-benzyl-1H-indazol-3-yl)-4-(4-methyl-piperazin-1-yl)-benzamide; N-[5-(3-fluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-benza- mide; N-[5-(2,5-difluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-- yl)benzamide; N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)be- nzamide; N-[5-(3-fluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-y- l)-2-nitrobenzamide; N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2- -nitro-benzamide; 2-amino-N-[5-(3-fluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-y- l)-benzamide; 2-amino-N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin- -1-yl)-benzamide; N-[5-(3-fluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2-(te- trahydro-pyran-4-ylamino)-benzamide; N-[5-(2,5-difluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2- -(tetrahydro-pyran-4-ylamino)-benzamide; N-[5-(3,5 difluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2-(tetrahyd- ro-pyran-4-ylamino)-benzamide; N-[5-(3-fluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2-(1-- methyl-piperidin-4-ylamino)-benzamide; N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2- -(1-methyl-piperidin-4-ylamino)-benzamide; N-[5-(3-fluoro-benzyl)-1H-indazol-3-yl]-2-(2-methoxy-1-methoxymethyl-ethy- lamino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-[5-(2,5-difluoro-benzyl)-1H-indazol-3-yl]-2-(2-methoxy-1-methoxymethyl-- ethylamino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-2-(2-methoxy-1-methoxymethyl-- ethylamino)-4-(4-methyl-piperazin-1-yl)-benzamide; 2-cyclohexylamino-N-[5-(3-fluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl-pip- erazin-1-yl)-benzamide; 2-cyclohexylamino-N-[543 ,5-difluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-benzamid- e; N-[5-(3-fluoro-benzyl)-1H-indazol-3-yl]-2-(4-hydroxy-cyclohexylamino)-4- -(4-methyl-piperazin-1-yl)-benzamide; N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-2-(4-hydroxy-cyclohexylamino)- -4-(4-methyl-piperazin-1-yl)-benzamide; N-[5-(3-fluoro-benzyl)-1H-indazol-3-yl]-2-isobutylamino-4-(4-methyl-piper- azin-1-yl)-benzamide; N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-2-isobutylamino-4-(4-methyl-p- iperazin-1-yl)-benzamide; 2-benzylamino-N-[5-(3-fluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl-piperaz- in-1-yl)-benzamide; 2-benzylamino-N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl-pip- erazin-1-yl)-benzamide; N-[5-(3-fluoro-benzyl)-1H-indazol-3-yl]-2-(2-methoxy-ethylamino)-4-(4-met- hyl-piperazin-1-yl)-benzamide; N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-2-(2-methoxy-ethylamino)-4-(4- -methyl-piperazin-1-yl)-benzamide; N-[5-(3-fluoro-benzyl)-1H-indazol-3-yl]-2-(2-methoxy-1-methyl-ethylamino)- -4-(4-methyl-piperazin-1-yl)-benzamide; N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-2-(2-methoxy-1-methyl-ethylam- ino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-[5-(3-fluoro-benzyl)-1H-indazol-3-yl]-2-((S)-2-methoxy-1-methyl-ethylam- ino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-2-((S)-2-methoxy-1-methyl-eth- ylamino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-[5-(3-fluoro-benzyl)-1H-indazol-3-yl]-2-((R)-2-methoxy-1-methyl-ethylam- ino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-2-((R)-2-methoxy-1-methyl-eth- ylamino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-[5-(3-fluoro-benzyl)-1H-indazol-3-yl]-2-(2-methoxy-1,1-dimethyl-ethylam- ino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-2-(2-methoxy-1,1-dimethyl-eth- ylamino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-[5-(3-fluoro-benzyl)-1H-indazol-3-yl]-2-(3-methoxy-propylamino)-4-(4-me- thyl-piperazin-1-yl)-benzamide; N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-2-(3-methoxy-propylamino)-4-(- 4-methyl-piperazin-1-yl)-benzamide; N-[5-(3-fluoro-benzyl)-1H-indazol-3-yl]-2-(2-fluoro-ethylamino)-4-(4-meth- yl-piperazin-1-yl)-benzamide; N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-2-(2-fluoro-ethylamino)-4-(4-- methyl-piperazin-1-yl)-benzamide; N-[5-(3-fluoro-benzyl)-1H-indazol-3-yl]-2-(3-fluoro-propylamino)-4-(4-met- hyl-piperazin-1-yl)-benzamide; N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-2-(3-fluoro-propylamino)-4-(4- -methyl-piperazin-1-yl)-benzamide; N-[5-(3-fluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2-phe- nylamino-benzamide; N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2- -phenylamino-benzamide; 1H-pyrrole-2-carboxylic acid[2-[5-(3-fluoro-benzyl)-1H-indazol-3-ylcarbamoyl]-5-(4-methyl-piperaz- in-1-yl)-phenyl]-amide; 1H-pyrrole-2-carboxylic acid[2-[5-(3,5-difluoro-benzyl)-1H-indazol-3-ylcarbamoyl]-5-(4-methyl-pip- erazin-1-yl)-phenyl]-amide; 1H-pyrrole-3-carboxylic acid[2-[5-(3-fluoro-benzyl)-1H-indazol-3-ylcarbamoyl]-5-(4-methyl-piperaz- in-1-yl)-phenyl]-amid; 1H-pyrrole-3-carboxylic acid[2-[5-(3,5-difluoro-benzyl)-1H-indazol-3-ylcarbamoyl]-5-(4-methyl-pip- erazin-1-yl)-phenyl]-amide; N-[5-(3-fluoro-benzyl)-1H-indazol-3-yl]-2-methanesulfonylamino-4-(4-methy- l-piperazin-1-yl)-benzamide; N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-2-methanesulfonylamino-4-(4-m- ethyl-piperazin-1-yl)-benzamide; 2-fluoro-N-[5-(3-fluoro-benzyl)-1H-indazol-3-yl]-5-(tetrahydro-pyran-4-yl- amino)-benzamide; N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-2-fluoro-5-(tetrahydro-pyran-- 4-ylamino)-benzamide; 2-fluoro-N-[5-(3-fluoro-benzyl)-1H-indazol-3-yl]-5-(2-methoxy-ethylamino)- -benzamide; N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-2-fluoro-5-(2-methoxy-ethylam- ino)-benzamide; 4-[(3-dimethylamino-propyl)-methyl-amino]-N-[5-(3-ethoxy-benzyl)-1H-indaz- ol-3-yl]-2-nitro-benzamide; 2-amino-4-[(3-dimethylamino-propyl)-methyl-amino]-N-[5-(3-ethoxy-benzyl)-- 1H-indazol-3-yl]-benzamide; N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-4-[(3-dimethylamino-propyl)-m- ethyl-amino]-2-(tetrahydro-pyran-4-ylamino)-benzamide; N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-4-[(3-dimethylamino-propyl)-m- ethyl-amino]-2-(2-methoxy-1-methoxymethyl-ethylamino)-benzamide; 2-amino-N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-4-[(3-dimethylamino-p- ropyl)-methyl-amino]-benzamide; N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-4-[(3-dimethylamino-propyl)-m- ethyl-amino]-benzamide; N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-4-[(3-dimethylamino-propyl)-m- ethyl-amino]-2-nitro-benzamide; N-{5-[(3,5-difluoro-phenyl)-hydroxy-methyl]-1H-indazol-3-yl}-4-(4-methyl-- piperazin-1-yl)-2-(tetrahydro-pyran-4-ylamino)-benzamide; N-{5-[(3,5-difluoro-phenyl)-hydroxy-methyl]-1H-indazol-3-yl}-2-(2-methoxy- -1 -methoxymethyl-ethylamino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-{5-[(3,5-difluoro-phenyl)-hydroxy-methyl]-1H-indazol-3-yl}-4-(4-methyl-- piperazin-1-yl)-benzamide; N-{5-[(3,5-difluoro-phenyl)-hydroxy-methyl]-1H-indazol-3-yl}-2-(2-methoxy- -ethylamino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-{5-[(3,5-difluoro-phenyl)-hydroxy-methyl]-1H-indazol-3-yl}-2-(3-methoxy- -propylamino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-{5-[(3,5-difluoro-phenyl)-hydroxy-methyl]-1H-indazol-3-yl}-2-(2-methoxy- -1,1-dimethyl-ethylamino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-{5-[(3,5-difluoro-phenyl)-hydroxy-methyl]-1H-indazol-3-yl}-2-(2-fluoro-- ethylamino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-{5-[(3-ethoxy-phenyl)-hydroxy-methyl]-1H-indazol-3-yl}-4-(4-methyl-pipe- razin-1-yl)-2-nitro-benzamide; N-{5-[(3,5-difluoro-phenyl)-methoxy-methyl]-1H-indazol-3-yl}-4-(4-methyl-- piperazin-1-yl)-2-(tetrahydro-pyran-4-ylamino)-benzamide; N-{5-[(3,5-difluoro-phenyl)-methoxy-methyl]-1H-indazol-3-yl}-2-(2-methoxy- -1-methoxymethyl-ethylamino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-{5-[(3,5-difluoro-phenyl)-methoxy-methyl]-1H-indazol-3-yl}-4-(4-methyl-- piperazin-1-yl)-benzamide; N-{5-[(3,5-difluoro-phenyl)-methoxy-methyl]-1H-indazol-3-yl}-2-(2-methoxy- -ethylamino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-{5-[(3,5-difluoro-phenyl)-methoxy-methyl]-1H-indazol-3-yl}-2-(3-methoxy- -propylamino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-{5-[(3,5-difluoro-phenyl)-methoxy-methyl]-1H-indazol-3-yl}-2-(2-methoxy- -1,1-dimethyl-ethylamino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-{5-[(3,5-difluoro-phenyl)-methoxy-methyl]-1H-indazol-3-yl}-2-(2-fluoro-- ethylamino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-{5-[1-(3,5-difluoro-phenyl)-ethyl]-1H-indazol-3-yl}-4-(4-methyl-piperaz- in-1-yl)-2-(tetrahydro-pyran-4-ylamino)-benzamide; N-{5-[1-(3,5-difluoro-phenyl)-ethyl]-1H-indazol-3-yl}-2-(2-methoxy-1-meth- oxymethyl-ethylamino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-{5-[(3,5-difluoro-phenyl)-ethyl]-1H-indazol-3-yl}-4-(4-methyl-piperazin- -1-yl)-benzamide; N-{5-[(3,5-difluoro-phenyl)-ethyl]-1H-indazol-3-yl}-2-(2-methoxy-ethylami- no)-4-(4-methyl-piperazin-1-yl)-benzamide; N-{5-[(3,5-difluoro-phenyl)-ethyl]-1H-indazol-3-yl}-2-(3-methoxy-propylam- ino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-{5-[(3,5-difluoro-phenyl)-ethyl]-1H-indazol-3-yl}-2-(2-methoxy-1,1-dime- thyl-ethylamino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-{5-[(3,5-difluoro-phenyl)-ethyl]-1H-indazol-3-yl}-2-(2-fluoro-ethylamin- o)-4-(4-methyl-piperazin-1-yl)-benzamide; N-{5-[1-(3,5-difluoro-phenyl)-1-methyl-ethyl]-1H-indazol-3-yl}-4-(4-methy- l-piperazin-1-yl)-2-(tetrahydro-pyran-4-ylamino)-benzamide; N-{5-[1-(3,5-difluoro-phenyl)-1-methyl-ethyl]-1H-indazol-3-yl}-2-(2-metho- xy-1-methoxymethyl-ethylamino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-{5-[1-(3,5-difluoro-phenyl)-1-methyl-ethyl]-1H-indazol-3-yl}-4-(4-methy- l-piperazin-1-yl)-benzamide; N-{5-[1-(3,5-difluoro-phenyl)-1-methyl-ethyl]-1H-indazol-3-yl}-2-(2-metho- xy-ethylamino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-{5-[1-(3,5-difluoro-phenyl)-1-methyl-ethyl]-1H-indazol-3-yl}-2-(3-metho- xy-propylamino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-{5-[1-(3,5-difluoro-phenyl)-1-methyl-ethyl]-1H-indazol-3-yl}-2-(2-metho- xy-1,1 -dimethyl-ethylamino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-{5-[1-(3,5-dfluoro-phenyl)-1-methyl-ethyl]-1H-indazol-3-yl}-2-(2-fluoro- -ethylamino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-(4-methyl-1,4-diazepan-1-yl)- -2-(tetrahydro-2H-pyran-4-ylamino)benzamide; N-[5-(3,5-Difluoro-benzyl)-1H-indazol-3-yl]-4-[(2-dimethylamino-ethyl)-me- thyl-amino]-2-(tetrahydro-pyran-4-ylamino)-benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-[4-(dimethylamino)piperidin-- 1-yl]-2-(tetrahydro-2H-pyran-4-ylamino)benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-[(2S)-2-(pyrrolidin-1-ylmeth- yl)pyrrolidin-1-yl]-2-(tetrahydro-2H-pyran-4-ylamino)benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-3-(4-methylpiperazin-1-yl)benz- amide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-{[(2S)-1-methylpyrroli- din-2-yl]methoxy}-2-(tetrahydro-2H-pyran-4-ylamino)benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-[(1-methylpiperidin-4-yl)oxy- ]-2-(tetrahydro-2H-pyran-4-ylamino)benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-[2-(dimethylamino)ethoxy]-2-- (tetrahydro-2H-pyran-4-ylamino)benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-{[(3S)-1-methylpyrrolidin-3-- yl]oxy}-2-(tetrahydro-2H-pyran-4-ylamino)benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-(piperazin-1-yl)-2-(tetrahyd- ro-2H-pyran-4-ylamino)benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-(4-methylpiperazin-1-yl)-2-{- [cis-4-(trifluoromethyl)cyclohexyl]amino}benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-(4-methylpiperazin-1-yl)-2-{- [trans-4-(trifluoromethyl)cyclohexyl]amino}benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-2-fluoro-4-(4-methylpiperazin-- 1-yl)benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-1-(piperidin-4-yl)-1H-pyrazole- -4-carboxamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-2-[(cis-4-hydroxycyclohexyl)am- ino]-4-(4-methylpiperazin-1-yl)benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-2-[(trans-4-hydroxycyclohexyl)- amino]-4-(4-methylpiperazin-1-yl)benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-2-[(2-hydroxyethyl)amino]-4-(4- -methylpiperazin-1-yl)benzamide; 2-[(azetidin-3-ylmethyl)amino]-N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]- -4-(4-methylpiperazin-1-yl)benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-2-{[(1-methylazetidin-3-yl)met- hyl]amino}-4-(4-methylpiperazin-1-yl)benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-[(1-methylpiperidin-4-yl)ami- no]-2-[tetrahydro-2H-pyran-4-ylamino]benzamide; 4-[(azetidin-3-ylmethyl)amino]-N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]- -2-(tetrahydro-2H-pyran-4-ylamino)benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-2-[(1-methylpiperidin-4-yl)ami- no]benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-2-[(1-methylpiperidin-4-yl)ami- no]-4-(morpholin-4-yl)benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-2-methoxy-4-(4-methylpiperazin- -1-yl)benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-5-(4-methylpiperazin-1-yl)-3-(- tetrahydro-2H-pyran-4-ylamino)pyridine-2-carboxamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-6-(4-methylpiperazin-1-yl)-2-(- tetrahydro-2H-pyran-4-ylamino)pyridine-3-carboxamide; 1-[4-{[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]carbamoyl}-3-(tetrahydro-2H- -pyran-4-ylamino)benzyl]piperidine; N-[5(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-{[(2-methoxyethyl)(methyl)ami- no]methyl}-2-(tetrahydro-2H-pyran-4-ylamino)benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-(pyrrolidin-1-ylmethyl)-2-(t- etrahydro-2H-pyran-4-ylamino)benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-(morpholin-4-ylmethyl)-2-(te- trahydro-2H-pyran-4-ylamino)benzamide; 4-(azetidin-1-ylmethyl)-N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-2-(tet- rahydro-2H-pyran-4-ylamino)benzamide; N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-2-fluoro-5-(4-methyl-piperazi- n-1-ylmethyl)-benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-2-fluoro-5-{[(2S)-2-(pyrrolidi- n-1-ylmethyl)pyrrolidin-1-yl]methyl}benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-2-fluoro-5-(morpholin-4-ylmeth- yl)benzamide; N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-2-fluoro-5-((S)-2-pyrrolidin-- 1-ylmethyl-pyrrolidine-1-carbonyl)-benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-{[(2R)-2-(pyrrolidin-1-ylmet- hyl)pyrrolidin-1-yl]carbonyl}benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-{[(2S)-2-(pyrrolidin-1-ylmet- hyl)pyrrolidin-1-yl]carbonyl}benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-{[4-(pyrrolidin-1-yl)piperid- in-1-yl]carbonyl}benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-{[(2S)-2-(pyrrolidin-1-ylmet- hyl)pyrrolidin-1-yl]carbonyl}-2-(tetrahydro-2H-pyran-4-ylamino)benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-{[(2R)-2-(pyrrolidin-1-ylmet- hyl)pyrrolidin-1-yl]carbonyl}-2-(tetrahydro-2H-pyran-4-ylamino)benzamide; N.sup.1-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-N.sup.4-[2-(dimethylamin- o)ethyl]-N.sup.4-methyl-2-(tetrahydro-2H-pyran-4-ylamino)benzene-1,4-dicar- boxamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-{[4-(propan-2-yl)pi- perazin-1-yl]carbonyl}-2-(tetrahydro-2H-pyran-4-ylamino)benzamide; N.sup.1-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-N.sup.4-[2-(dimethylamin- o)ethyl]-2-(tetrahydro-2H-pyran-4-ylamino)benzene-1,4-dicarboxamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-[(4-methylpiperazin-1-yl)car- bonyl]-2-(tetrahydro-2H-pyran-4-ylamino)benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-{[4-(dimethylamino)piperidin- -1-yl]carbonyl}-2-(tetrahydro-2H-pyran-4-ylamino)benzamide; N.sup.1-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-N.sup.4-(1-methylpiperid- in-4-yl)-2-(tetrahydro-2H-pyran-4-ylamino)benzene-1,4-dicarboxamide; N-[5-(2-methyl-5-fluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-- yl)-2-(tetrahydro-pyran-4-ylamino)-benzamide; 4-(4-methylpiperazin-1-yl)-N-[5-(pyridin-3-ylmethyl)-1H-indazol-3-yl]-2-(- tetrahydro-2H-pyran-4-ylamino)benzamide; N-[5-benzyl-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2-(tetrahydro-py- ran-4-ylamino)-benzamide; ethyl 4-{[2-{[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]carbamoyl}-5-(4-methylpipe- razin-1-yl)phenyl]amino}piperidine-1-carboxylate; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-(4-methylpiperazin-1-yl)-2-(- piperidin-4-ylamino)benzamide; ethyl 5-(3,5-difluorobenzyl)-3-({[4-(4-methylpiperazin-1-yl)-2-(tetrahydro-2H-p- yran-4-ylamino)phenyl]carbonyl}amino)-1H-indazole-1 -carboxylate; N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-2-((S)-2-methoxy-1 -methyl-ethylamino)-4-(4-methyl-piperazin-1-yl)-benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-[(2R)-2-(pyrrolidin-1-ylmeth- yl)pyrrolidin-1-yl]-2-(tetrahydro-2H-pyran-4-ylamino)benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-{[(2R)-1-methylpyrrolidin-2-- yl]methoxy}-2-(tetrahydro-2H-pyran-4-ylamino)benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-{[(3R)-1-methylpyrrolidin-3-- yl]oxy}-2-(tetrahydro-2H-pyran-4-ylamino)benzamide; N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-2-fluoro-5-{[(2R)-2-(pyrrolidi- n-1-ylmethyl)pyrrolidin-1-yl]methyl}benzamide, and N-[5-(3,5-difluoro-benzyl)-1H-indazol-3-yl]-2-fluoro-5-((R)-2-pyrrolidin-- 1-ylmethyl-pyrrolidine-1-carbonyl)-benzamide. 7. A compound of or a pharmaceutically acceptable salt of N-[5-(3,5difluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2-- (tetrahydro-pyran-4-ylamino)-benzamide. 8. A process for preparing a compound of formula (I) as defined in claim 1, characterized in that the process comprises: i) reducing a carbonyl compound of formula (II): ##STR00135## wherein Ar, R, R1, R2, and R3 are as defined in claim 1, to give a compound of formula (I.sub.A), (I.sub.B) or (l.sub.C): ##STR00136## wherein Ar, R, R1, R2, R3 and R' are as defined in claim 1; or i') reacting a compound of formula (III.sub.A), (III.sub.B), (III.sub.C) or (III.sub.D): ##STR00137## wherein R, R1, R2, R3, R' and R'' are as defined in claim 1, with a compound of formula (IV): ##STR00138## wherein Ar is as defined in claim 1 and Y represents hydroxy, or a suitable leaving group comprising halogen, to give a compound of formula (I), as defined in claim 1; or i'') deprotecting a compound of formula (XXII.sub.A), (XXII.sub.C) or (XXII.sub.D): ##STR00139## wherein Ar, R, R1, R2, R3, R' and R'' are as defined in claim 1 and PG is a suitable protecting group comprising benzyl, p-methoxybenzyl, o,p-dimethoxybenzyl, or triphenylmethyl, to give a compound of formula (I.sub.A), (I.sub.C) or (I.sub.D): ##STR00140## wherein Ar, R, R1, R2, R3, R' and R'' are as defined in claim 1, optionally separating the resulting compound into the single optical isomers, converting the compound of formula (I) into a different compound of formula (I), andor into a pharmaceutically acceptable salt if desired. 9. A process for preparing a compound of formula (I.sub.A) according to claim 8, characterized in that the compound of formula (III.sub.A) as defined in claim 8, is prepared according to the following steps: j) reducing a compound of formula (XI): ##STR00141## in the presence of a suitable reagent comprising Nal and Me.sub.3SiCl, to give a compound of formula (XIV): ##STR00142## wherein R, R1, R2 and R3 are as defined above; or k) reacting a boronic acid compound of formula (XV): ##STR00143## wherein R1, R2 and R3 are as defined above, with a compound of formula (XVI): ##STR00144## wherein W represents a halogen atom, comprising bromine or iodine, or a suitable leaving group like sulphonates, comprising methanesulphonate or trifluoromethanesulphonate, or phosphates in the presence of a suitable catalyst comprising a Palladium catalyst, to give a compound of formula (XIV) as defined above; l) reacting the resulting compound of formula (XIV) with hydrazine hydrate, to give a compound of formula (III.sub.A) as defined in claim 8. 10. A process for the preparation of a compound of formula (I.sub.A),(I.sub.C) or (I.sub.D) as defined in claim 8, characterized in that a compound of formula (XXII.sub.A), (XXII.sub.C) or (XXII.sub.D) as defined in claim 8, is prepared according to the following steps: r) protecting a compound of formula (III.sub.A), (III.sub.C) or (III.sub.D) as defined in claim 8, to give a compound of formula (XXIV.sub.A), (XXIV.sub.C) or (XXIV.sub.D): ##STR00145## wherein PG.sub.1 is a suitable protecting group comprising trifluoroacetyl group; s) protecting the resulting compound of formula (XXIV.sub.A), (XXIV.sub.C) or (XXIV.sub.D), to give a compound of formula (XXV.sub.A), (XXV.sub.C) or (XXV.sub.D): ##STR00146## wherein R, R1, R2,R3, R', R'' and PG.sub.1 are as defined above and PG is as defined in claim 8; t) removing the protecting group PG.sub.1 from the resulting compound of formula (XXV.sub.A), (XXV.sub.C) or (XXV.sub.D), to give a compound of formula (XXVI.sub.A), (XXVI.sub.C) or (XXVI.sub.D): ##STR00147## wherein R, R1, R2, R3, R', R'' are defined in claim 1 and PG is defined in claim 8; u) reacting the resulting compound of formula (XXVI.sub.A), (XXVI.sub.C) or (XXVI.sub.D), with a compound of formula (IV) as defined in claim 8, to give a compound of formula (XXII.sub.A), (XUI.sub.C) or (XXII.sub.D) as defined in claim 8. 11. A process for preparing a compound of formula (I) according to claim 8 characterized in that the optional conversion of a compound of formula (I) into another compound of formula (I), is carried out by one or more of the following reactions: i) reducing a compound of formula (I) wherein Ar is a substituted aryl and one of the substituents is NO.sub.2, for obtaining a compound of formula (I) wherein such substituent is NH.sub.2; ii) acylating a compound of formula (I), wherein Ar is a substituted aryl and one of the substituents is NH.sub.2, by reaction with a compound of formula (XXVII) or (XXVIII), ##STR00148## followed by selective deprotection of the acyl group on the pyrazole ring for obtaining a compound of formula (I) wherein such substituent is a NHCOR4 or NHSO.sub.2R4 residue, iii) reacting a compound of formula (I), wherein Ar is a substituted aryl and one of the substituents is NH.sub.2, with a suitable aldehyde or ketone in the presence of a reducing agent, for obtaining a compound of formula (I), wherein such substituent is a NR5R6 group, wherein one of the R5 or R6 are hydrogen and the other is an optionally further substituted straight or branched C.sub.1-C.sub.6 alkyl, --C.sub.3-C.sub.6 cycloalkyl, heterocyclyl, aryl, R8R9N--C.sub.2-C.sub.6 alkyl, --R8O--C.sub.2-C.sub.6 alkyl. 12. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof, as defined in claim 1, and at least one pharmaceutically acceptable excipient, carrier and/or diluent. 13. A product or kit comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, as defined in claim 1, or pharmaceutical compositions comprising a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof, as defined in claim 1, and at least one pharmaceutically acceptable excipient, carrier andor diluent and one or more chemotherapeutic agents, as a combined preparation for simultaneous, separate or sequential use in anticancer therapy. 14. An intermediate of the formula (XXII.sub.A), (XXII.sub.C) or (XXII.sub.D): ##STR00149## wherein R' is C.sub.1-C.sub.6 alkyl and R'' is hydrogen; Ar is phenyl, pyrazolyl or pyridyl optionally substituted with one or more substituents independently selected from halogen, nitro, COR4, NR5R6, OR7 NHSO.sub.2R10, a straight or branched C.sub.1-C.sub.6 alkyl optionally substituted by a heterocyclyl, in its turn optionally substituted by a straight or branched C.sub.1-C.sub.6 alkyl or an heterocyclylalkyl, or a heterocyclyl optionally substituted by a straight or branched C.sub.1-C.sub.6 alkyl, in its turn optionally substituted by a heterocyclyl or a C.sub.1-C.sub.6 alkoxycarbonyl, or a C.sub.1-C.sub.6 dialkylamino: R4 is NR5R6, or a heterocyclyl, optionally further substituted by a straight or branched C.sub.1-C.sub.6 alkyl, heterocyclylalkyl, heterocyclyl or a C.sub.1-C.sub.6 dialkylamino; R5 and R6 are independently hydrogen, R8R9N--C.sub.2-C.sub.6 alkyl, R8O--C.sub.2-C.sub.6 alkyl, a straight or branched C.sub.1-C.sub.6 alkyl optionally further substituted by C.sub.1-C.sub.6 alkoxy, --C.sub.1-C.sub.6 dialkylamino, halogen, phenyl, hydroxyl or heterocyclyl in its turn optionally substituted by alkyl, C.sub.3-C.sub.6 cycloalkyl optionally substituted by hydroxyl or trifluoro C.sub.1-C.sub.6 alkyl, heterocyclyl optionally substituted by C.sub.1-C.sub.6 alkyl in its turn optionally substituted by halogen or heterocyclyl, C.sub.1-C.sub.6 alkoxycarbonyl, C.sub.1-C.sub.6 dialkylamino, heterocyclyl, or phenyl, or R5 and R6, taken together with the nitrogen atom to which they are bonded, may form a heterocyclyl group optionally substituted by a straight or branched C.sub.1-C.sub.6 alkyl, in its turn optionally substituted by a heterocyclyl or a C.sub.1-C.sub.6 alkoxycarbonyl, a C.sub.1-C.sub.6 dialkylamino or a heterocyclyl; R7 is straight or branched C.sub.1-C.sub.6 alkyl, optionally substituted by C.sub.1-C.sub.6 dialkylamino or heterocyclyl in its turn substituted by C.sub.1-C.sub.6 alkyl; R8 and R9 are independently an optionally further substituted straight or branched C.sub.1-C.sub.6 alkyl; R10 is an optionally further substituted straight or branched C.sub.1-C.sub.6 alkyl; R is phenyl or pyridyl optionally substituted halogen or straight or branched C.sub.1-C.sub.6 alkyl; R1, R2 and R3 are hydrogen; or optical isomers, tautomers or pharmaceutically acceptable salt thereof and PG is a suitable protecting group such as benzyl, p-methoxybenzyl, o,p-dimethoxybenzyl, or triphenylmethyl, to give a compound of formula (I.sub.A), (I.sub.C) or (I.sub.D): ##STR00150## 15. A compound of formula (XXVII): ##STR00151## wherein R' is C.sub.1-C.sub.6 alkyl and R'' is hydrogen; Ar is phenyl, pyrazolyl or pyridyl optionally substituted with one or more substituents independently selected from halogen, nitro, COR4, NR5R6, OR7, NHSO.sub.2R10, a straight or branched C.sub.1-C.sub.6 alkyl optionally substituted by a heterocyclyl, in its turn optionally substituted by a straight or branched C.sub.1-C.sub.6 alkyl or an heterocyclylalkyl, or a heterocyclyl optionally substituted by a straight or branched C.sub.1-C.sub.6 alkyl, in its turn optionally substituted by a heterocyclyl or a C.sub.1-C.sub.6 alkoxycarbonyl, or a C.sub.1-C.sub.6 dialkylamino: R4 is NR5R6, or a heterocyclyl, optionally further substituted by a straight or branched C.sub.1-C.sub.6 alkyl, heterocyclylalkyl, heterocyclyl or a C.sub.1-C.sub.6 dialkylamino; R5 and R6 are independently hydrogen, R8R9N--C.sub.2-C.sub.6 alkyl, R8O--C.sub.2-C.sub.6 alkyl, a straight or branched C.sub.1-C.sub.6 alkyl optionally further substituted by C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 dialkylamino, halogen, phenyl, hydroxyl or heterocyclyl in its turn optionally substituted by alkyl, C.sub.3-C.sub.6 cycloalkyl optionally substituted by hydroxyl or trifluoro C.sub.1-C.sub.6 alkyl, heterocyclyl optionally substituted by C.sub.1-C.sub.6 alkyl in its turn optionally substituted by halogen or heterocyclyl, C.sub.1-C.sub.6 alkoxycarbonyl, C.sub.1-C.sub.6 dialkylamino, heterocyclyl, or phenyl, or R5 and R6, taken together with the nitrogen atom to which they are bonded, may form a heterocyclyl group optionally substituted by a straight or branched C.sub.1-C.sub.6 alkyl, in its turn optionally substituted by a heterocyclyl or a C.sub.1-C.sub.6 alkoxycarbonyl, a C.sub.1-C.sub.6 dialkylamino or a heterocyclyl; R7 is straight or branched C.sub.1-C.sub.6 alkyl, optionally substituted by C.sub.1-C.sub.6 dialkylamino or heterocyclyl in its turn substituted by C.sub.1-C.sub.6 alkyl; R8 and R9 are independently an optionally further substituted straight or branched C.sub.1-C.sub.6 alkyl; R10 is an optionally further substituted straight or branched C.sub.1-C.sub.6 alkyl; R is phenyl or pyridyl optionally substituted halogen or straight or branched C.sub.1-C.sub.6 alkyl; R1, R2 and R3 are hydrogen; or optical isomers, tautomers or pharmaceutically acceptable salt thereof and PG.sub.2 is ethoxycarbonyl or 2-methoxyethylcarbonyl. 16. A process for preparing a compound of formula (XXVII) as defined in claim 15, characterized in that the process comprises: v) protecting a compound of formula (I), to give a compound of formula (XXVII): ##STR00152## wherein Ar, R, R1, R2 and R3 and PG.sub.2 are defined as in claim 15.