Nerviano Medical Sciences S.r.l.

Michele Modugno

Daniele Fancelli

Gabriella Traquandi

Chiara Marchionni

Maurizio Pulici

Fabio Zuccotto

Antonella Isacchi

Giovanni Cervi

Alessandra Badari

Stefano Nuvoloni

Rosita Lupi

Sonia Biondaro

Luisa Rusconi

Chiara Soncini

Jurgen Moll

Juergen Moll

Paolo Trifiro′

3,4-diarylpyrazole derivatives of formula (I) as defined in the specification, and pharmaceutically acceptable salts thereof, 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 disregulated protein kinase activity, like cancer. 

3,4-diarylpyrazoles as protein kinase inhibitors

The invention provides low molecular weight compounds, namely tetrahydropyrrolo[3,4-c]pyrazoles, showing a high affinity for the ATP pocket of ABL tyrosine kinase. These compounds are thus ATP-competitive tyrosine kinase inhibitors displaying a significant inhibitory potency also, and in particular, towards BCR-ABL inhibitor-resistant T315I ABL mutants. The compounds of the invention find a useful application in the treatment of BCR-ABL inhibitor-resistant ABL-mediated diseases, such as Imatinib-resistant chronic myelogenous leukemia. Moreover, the invention provides a screening method for the identification of compounds capable of binding the ATP pocket of a kinase protein, in particular of the T315I mutant ABL kinase.

Use of a kinase inhibitor for the treatment of particular resistant tumors

The invention provides low molecular weight compounds, namely 1H-thieno[2,3-c]pyrazoles, showing a high affinity for the ATP pocket of ABL tyrosine kinase. These compounds are thus ATP-competitive tyrosine kinase inhibitors displaying a significant inhibitory potency also, and in particular, towards BCR-ABL inhibitor-resistant T315I ABL mutants. The compounds of the invention find a useful application in the treatment of BCR-ABL inhibitor-resistant ABL-mediated diseases, such as Imatinib-resistant chronic myelogenous leukemia. Moreover, the invention provides a screening method for the identification of compounds capable of binding the ATP pocket of a kinase protein, in particular of the T315I mutant ABL kinase.

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Cernusco sul Naviglio, Italy

Michele Modugno