QUINAZOLINES AND AZAQUINAZOLINES AS DUAL INHIBITORS OF RAS/RAF/MEK/ERK AND PI3K/AKT/PTEN/MTOR PATHWAYS

摘要

The present application provides novel quinazolines and azaquinazolines and pharmaceutically acceptable salts thereof. Also provided are methods for preparing these compounds. These compounds are useful in for co-regulating RAS/RAF/MEK/ERK and PI3K/AKT/PTEN/mTOR pathways by administering a therapeutically effective amount of one or more of the compounds of formula (I), wherein X, Y, T and R4, and R6 to R8′ are defined herein, to a patient. By doing so, these compounds are effective in treating conditions associated with the dysregulation of the RAS/RAF/MEK/ERK and PI3K/AKT/PTEN/mTOR pathways. A variety of conditions can be treated using these compounds and include diseases which are characterized by abnormal cellular proliferation. In one embodiment/the disease is cancer.;

主权项

1. A compound of formula (I):wherein:
X is CH or N; Y is H, optionally substituted C1-C6 alkyl, OR1 or NR2R3; T is H or C1-C6 alkoxy; R1 is optionally substituted C1-C6 alkyl, optionally substituted (C1-C6 alkyl)OH, optionally substituted (C1-C6 alkyl)OC1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted (C1-C6 alkyl)NH2, optionally substituted (C1-C6 alkyl)CO2H, or optionally substituted (C1-C6 alkyl)CONH2; R2 and R3 are joined to form an optionally substituted heterocycle; R4 is optionally substituted morpholine; R6 is optionally substituted aryl or optionally substituted heteroaryl; R7 is optionally substituted aryl, optionally substituted C1-C6 alkyl, or optionally substituted heteroaryl; R8 is H or halogen; and R8′ is halogen.