Derivatives of 8-carbamoyl-2- (pyrid-6-yl 2,3-disubstituted) -1,2,3,4-tetrahydroisoquinoline as inducing agents for apoptosis for the treatment of cancer and immune and autoimmune diseases
WANG, Le,DOHERTY, George,WANG, Xilu,TAO, Zhi-Fu,BRUNKO, Milan,KUNZER, Aaron R.,WENDT, Michael D.,SONG, Xiaohong,FREY, Robin,HANSEN, Todd M.,SULLIVAN, Gerard M.,JUDD, Andrew,SOUERS, Andrew
申请号：
ES12780605
公开号：
ES2598877T3
申请日:
2012.10.11
申请国别(地区):
ES
年份:
2017
代理人:
摘要：
A compound having Formula (I) ** Formula ** or a therapeutically acceptable salt thereof, wherein X is benzo [d] thiazolyl, thiazolo [5,4-b] pyridinyl, thiazolo [4,5-c] pyridinyl, imidazo [1,2-a] pyridinyl, thiazolo [5,4- c] pyridinyl, thiazolo [4,5-b] pyridinyl, imidazo [1,2-a] pyrazinyl, or imidazo [1,2-b ] pyridazinyl； Y1 is pyrrolyl, pyrazolyl, triazolyl or pyridinyl； wherein Y1 is optionally substituted with one, or two substituents independently selected from the group consisting of R5, CN, F, Cl, Br and I； L1 is selected from the group consisting of (CR6R7) q, (CR6R7) s-LOC6R7) r, (CR6R7) sS- (CR6R7) r, (CR6R7) s-SO) 2- (CR6R7) r, (CR6R7) s -NR6AC (O) - (CR6R7) r, (CR6R7) sC (O) NR6A- (CR6R7) r, (CR6R7) s-NR6A- (CR6R7) ry (CR6R7) s- SO) 2NR6A- (CR6R7) r； Y2 is C8-C14 cycloalkyl or C8-C14 heterocycloalkyl； wherein Y2 is optionally substituted with one, two, or three substituents independently selected from the group consisting of R8, O8, SO2R8, CO (O) R8, OH, F, Cl, Br and I； Z1 is selected from the group consisting of ** Formula ** R1 is absent: R2, in each case, is independently deuterium or C1-C6 alkyl； R3 is absent； R5, in each case, is independently C1-C6 alkyl； R6A is independently selected from the group consisting of hydrogen and C1-C6 alkyl； R6 and R7, in each case, are each independently hydrogen； R8, in each case, is independently selected from the group consisting of C1-C6 alkyl, heterocyclyl and cycloalkyl； wherein R8 C1-C6 alkyl is optionally substituted with a substituent independently selected from the group consisting of R16, O16, SO2R16, and NHR16； Rk, in each case, is independently selected from the group consisting of C1-C6 alkyl, C3-C7 heterocycloalkyl, C3-C7 cycloalkyl and C1-C6 haloalkyl； R16, in each case, is independently selected from the group consisting of C1-C4 alkyl, phenyl, and heterocycloalkyl； wherein R16 C1-C4 alkyl is optionally substituted with a substituent independently selected from the group consisting of OCH3, OCH2CH2OC
