QUINAZOLINE DERIVATIVES AS TAM FAMILY KINASE INHIBITORS

摘要

Disclosed are compounds, compositions and methods for treating diseases, syndromes, conditions and disorders that are affected by the modulation of the activity of, e.g., the inhibition of, one or more members of the TAM family kinases.

主权项

1. A compound of formula (I): wherein: X is selected from —C(R9)2—, —N(R10)—, —O—, and —S(O)t— where t is 0, 1, or 2; Y and Z are independently selected from —C(R9)2—, —N(R10)—, —O—, —S(O)t— where t is 0, 1, or 2, and a heterocyclic moiety which contains 1 to 3 heteroatoms independently selected from O, N and S; R1 is selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, heterocyclyl, heteroaryl, cyano, amino, alkoxy, and hydroxyl; R2 and R3 are independently selected from hydrogen, alkyl, aralkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, halo, heterocyclyl, heterocyclylalkyl, alkoxy and alkoxyalkyl; R4 is selected from alkyl, aralkyl, alkenyl, aralkenyl, alkynyl, aralkynyl, cycloalkyl, cycloalkylalkyl and haloalkyl; or R4 is a 5-membered monocyclic heteroaryl moiety which contains 1 to 3 heteroatoms independently selected from O, N and S wherein the heteroaryl moiety may be substituted with one or more substituents selected from alkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, halo, cyano, amino, alkoxy, hydroxyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl and Q-L-R4a, where R4 is not pyrazole; Q is a direct bond, or a straight or branched alkylene chain; L is selected from —N(R10)—, —O—, —C(O)—, —C(O)O—, —S(O)t— where t is 0, 1, or 2, —CON(R10)—, —N(R10)CO—, —SO2N(R10)—, —N(R10)SO2—, and —N(R10)CON(R10)—; R4a is selected from alkyl, aralkyl, alkenyl, aralkenyl, alkynyl, aralkynyl, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, heteroaryl, and heterocyclyl; R5 and R6 are independently selected from hydrogen, alkyl, aralkyl, alkenyl, aralkenyl, alkynyl, aralkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocyclyl, heterocyclylalkyl, alkoxyalkyl, alkylaminoalkyl, and —R7—V—R8 where V is selected from —N(R10)—, or —O—; R7 is a straight or branched alkylene chain; R8 is selected from hydrogen, alkyl, aralkyl, alkenyl, aralkenyl, alkynyl, aralkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocyclyl, heterocyclylalkyl, alkoxyalkyl, and alkylaminoalkyl; R9 is selected from hydrogen, alkyl, halo, and haloalkyl; R10 is selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, and haloalkyl; a stereoisomer, enantiomer or tautomer thereof, an isotopically enriched derivative thereof, a pharmaceutically acceptable salt thereof, or a prodrug thereof.