Substituted pyrimidinyl and pyridinyl-pyrrolopyridinones, process for their preparation and their use as kinase inhibitors

摘要

The present invention relates to substituted pyrimidinyl- and pyridinylpyrrolopyridinone compounds which modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity, in particular RET family kinases. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing pharmaceutical compositions containing these compounds.

主权项

1. A compound of formula (I), wherein X is CH or N; R1 is H or NHR3, wherein R3 is H, an optionally substituted group selected from straight or branched C1-C6 alkyl, heterocyclyl and COR′, wherein R′ is an optionally substituted group selected from straight or branched C1-C6 alkyl, a C3-C6 carbocyclyl, aryl and heteroaryl; L1 is CH2—CH2, CH═CH or C≡C; Q is an optionally substituted group selected from aryl and heteroaryl; L2 is C(RaRb)NRa, C(RaRb)C(RaRb)NRa, C(RaRb)NRaC(RaRb), NRaC(RaRb), NRaC(RaRb)C(RaRb), COO, C(RaRb)COO, C(RaRb)C(RaRb)COO, SO2NRa, C(RaRb)SO2NRa, CONRa, C(RaRb)CONRa, C(RaRb)C(RaRb)CONRa, CONRaC(RaRb), CONRaC(RaRb)C(RaRb), C(RaRb)NRaCO, C(RaRb)C(RaRb)NRaCO, NRaCOC(RaRb),NRaCOC(RaRb)C(RaRb), OC(RaRb)CONRa, C(RaRb)OC(RaRb), OC(RaRb)(C(RaRb))nC(RaRb), wherein Ra and Rb are independently H or an optionally substituted straight or branched C1-C6 alkyl and n is 0 or 1; T is H or an optionally substituted group selected from straight or branched C1-C6 alkyl, C3-C6 carbocyclyl, heterocyclyl, aryl and heteroaryl; R2 is H or an optionally substituted group selected from straight or branched C1-C6 alkyl, C3-C6 carbocyclyl, heterocyclyl, aryl and heteroaryl; or pharmaceutically acceptable salts thereof.