PYRROLOPYRIMIDINE COMPOUNDS FOR THE TREATMENT OF CANCER

摘要

The ectopic expression of Mer receptor tyrosine kinase (Mer) has been identified as a tumor cell survival gene product in Acute Lymphoblastic Leukemia (ALL) cells and a potential cause of ALL chemoresistance. Hence, we investigated whether the development of small molecule Mer inhibitors was possible. A first aspect of the present invention is a compound (sometimes referred to as an “active compound” herein) of Formula I, IA, or IB.;

主权项

1. A compound of Formula I: wherein:
one of X and X′ is N and the other of X and X′ is C;one of the dashed lines in Formula I is a single bond and the other of the dashed lines in Formula I is a double bond;R1 is aryl or heteroaryl;R2 is —R5′R6, where R5′ is a covalent bond or C1 to C3 alkyl and R6 is cycloalkyl, heterocycloalkyl, aryl, heteroaryl or alkyl, and wherein R6 is optionally substituted from one to two times with independently selected polar groups;R3 is —NR7R8, where R7 and R8 are each independently selected from H, alkyl, arylalkyl; cycloalkylalkyl, heterocycloalkylalkyl, heteroaryalkyl, and alkoxyalkyl, each of which is optionally substituted one, two or three times with independently selected polar groups;or R2 and R3 together form a linking group;R4 is H, loweralkyl, halo, or loweralkoxy; andR5 is H, loweralkyl, halo, or loweralkoxy; or a pharmaceutically acceptable salt thereof.