| 摘要 |
The present invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. More specifically, the invention provides quinazolines and quinolines which inhibit, regulate and/or modulate kinase receptor, particularly c-Met, KDR, c-Kit, flt-3 and flt-4, signal transduction pathways related to the changes in cellular activities as mentioned above, compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions. The present invention also provides methods for making compounds as mentioned above, and compositions which contain these compounds. |
| 主权项 |
1. A process for preparing a compound of formula XXIb: comprising reaction of a compound of Formula XXIIb, with a compound of Formula XXIIIb: wherein: J is ═C(H)—; R2 is selected from —H, halogen, trihalomethyl, —CN, —NO2, —NH2, —OR3, —NR3R3, —S(O)0-2R3, —SO2NR3R3, —CO2R3, —C(O)NR3R3, —N(R3)SO2R3, —N(R3)C(O)R3, —N(R3)CO2R3, —C(O)R3, and optionally substituted C1-6alkyl; each R3 is independently selected from —H, —Si(R5)(R5)R5, optionally substituted lower alkyl, optionally substituted aryl, optionally substituted arylalkyl, and optionally substituted heteroarylalkyl; two R3, together with the nitrogen to which they are attached, form a four- to seven-membered heteroalicyclic, said four- to seven-membered heteroalicyclic optionally containing one additional heteroatom; when one said additional heteroatom is a nitrogen, then said nitrogen is optionally substituted with a group selected from —H, trihalomethyl, —SO2R5, —SO2NR5R5, —CO2R5, —C(O)NR5R5, —C(O)R5, and optionally substituted lower alkyl; each R20 is independently selected from —H, halogen, trihalomethyl, —CN, —NO2, —NH2, —OR3, —NR3R3, —S(O)0-2R3, —SO2NR3R3, —CO2R3, —C(O)NR3R3, —N(R3)SO2R3, —N(R3)C(O)R3, —N(R3)CO2R3, —C(O)R3, optionally substituted C1-6alkyl, optionally substituted aryl, optionally substituted aryl C1-6alkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclyl C1-6alkyl; two of R20, together with the atom or atoms to which they are attached, combine to form an optionally substituted three- to seven-membered heteroalicyclic; R50 is lower alkyl; and P1 is selected from chlorine, bromine, a toluene sulfonate, and trifluoromethansulfonate. |
