Pyrimidine compounds that inhibit anaplastic lymphoma kinase

摘要

A compound of formula I: ** Formula ** or a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a pharmaceutically acceptable salt of the stereoisomer, or a mixture thereof, wherein: X is selected from -CH2-, - N (H) -, -O-, or -S-; V is absent or is selected from -CH2-, -O-, -S-, or -NH-; where if V is -O-, -S- or -NH-, then r is 1 and q is 1; the subscript p is selected from 0, 1, 2, or 3, where X is CH2 if p is 0; the subscript q is selected from 0 or 1; subscript r is selected from 0 or 1; the symbol indicates that the link can be a single or double link; Z is a C6-C10 aryl or a 5-10 membered heteroaryl comprising 1, 2, 3 or 4 heteroatoms independently selected from O, S or N, wherein C6-C10 aryl or 5-10 heteroaryl members are unsubstituted or optionally substituted with 1, 2, 3, or 4 substituents independently selected from -Z ', -O-Z', -S-Z ', -NH-Z', -CH2Z ', -F, -Cl, -Br, -I, -C≡N, -NO2, -C1-C6 alkyl, -C2-C6 alkenyl, -C2-C6 alkynyl, -C1-alkylene C4) -OH, -NH2, -NH ((C1-C4) alkyl), -N ((C1-C4) alkyl) 2, - C ( = O) NH2, -C ( = O) NH ((C1-C4) alkyl), -C ( = O) N ((C1-C4) alkyl) 2, -C ( = O) NH-Z ', -SO2NH2, - SO2NH (alkyl of ( C1-C4)), -SO2N ((C1-C4) alkyl) 2, -SO2NH-Z ', -NHSO2-(C1-C4) alkyl, -NHSO2-Z', - NHC ( = O) - (C1-C4) -alkyl, -NHC ( = O) -Z ', -SO2-(C1-C4) -alkyl, -SO2-Z', -SO-(C1-C4) -alkyl- (C1-C4) -NH-C ( = O) -alkyl of (C1-C4), -CF3, -C ( = O) -alkyl of (C1-C4), -CO2H, -C ( = O) -Z ', -C ( = O) -O (C1-C4) -alkyl, -C ( = O) NH-alq (C1-C4) -UHylene, -C ( = O) NH-(C1-C4) alkylene -NH ((C1-C4) alkyl), - C ( = O) NH-alkylene of ( C1-C4) -N ((C1-C4) alkyl) 2, -C1-C4-alkylene-C ( = O) -C1-C4-alkyl, -C1-C4-alkylene - C ( = O) -O-(C1-C4) -alkyl,-(C1-C4) -alkylene-C ( = O) -OH, -OH, -O-(C1-C6) -alkyl, - SH, -C1-C6-Salkyl, -OCF3, or -OCHF2; and two adjacent substituents on C6-C10 aryl or 5-10 membered heteroaryl can join to form a 5- or 6-membered ring comprising 0, 1, or 2 heteroatoms selected from O, N, or S; and further wherein where the C6-C10 aryl and 5-10 membered heteroaryl may be monocyclic or bicyclic and further where both rings of a bicyclic C6-C10 aryl or a bicyclic 5-10 membered heteroaryl may be aromatic or one of the rings may be partially saturated and the other ring may be aromatic, and either the partially saturated ring or the aromatic ring may be attached to V, if present, or to the C atom bearing Rb and Rb 'if V is not present, or to the C atom bearing Ra and Ra 'if V is not present and q is 0, or to the N atom attached to C ( = O) if V is not present, q is 0, and r is 0; and further wherein, the partially saturated ring of a bicyclic C6-C10 aryl or a bicyclic 5-10 membered heteroaryl may include a -C ring member ( = O).