Derivatives of 8-carbamoyl-2- (pyrid-6-yl 2,3-disubstituted) -1,2,3,4-tetrahydroisoquinoline as apoptosis inducing agents for the treatment of cancer and immune and autoimmune disease

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) r (CR6R7) s- SO) 2NR6A- (CR6R7) r; Y2 is cycloalkyl or heterocycloalkyl C8-C14 C8-C14; 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 instance, it is independently deuterium or C1-C6 alkyl; R3 is absent; R5, in each instance, is independently C1-C6 alkyl; R6A are independently selected from the group consisting of hydrogen and C1-C6 alkyl; R6 and R7, in each case, they are each independently hydrogen; R8, at each occurrence, is independently selected from the group consisting of C1-C6, alkyl and cycloalkyl; wherein R8 is C1-C6 alkyl optionally substituted with a substituent independently selected from the group consisting of R16, O16, SO2R16, and NHR16; Rk, in each case independently selected from the group consisting of C1-C6 alkyl, C3-C7 heterocycloalkyl, C3-C7 and C1-C6 haloalkyl; R16, at each occurrence, is independently selected from the group consisting of C1-C4 alkyl, phenyl and heterocycloalkyl alkyl; wherein R16 is C1-C4 alkyl optionally substituted with a substituent independently selected from the group consisting of OCH3, OCH2CH2OCH3 and OCH2CH2NHCH3; q is 1 or 2; s is 0 or 1; r is 0 or 1; wherein the sum of syr is 0 or 1; m is 0: n is 0, 1, or 2; p is 0.