Dipicolylamine derivatives and their pharmaceutical uses

摘要

Dipicolylamine compounds of Formula (I) set forth herein. Also disclosed are pharmaceutical compositions containing metal ions and these compounds. Further disclosed is a method for treating a condition associated with cells containing inside-out phosphatidylserine, with these compounds.

主权项

1. A compound of formula (I):in which
each of A1, A2, A3, A4, A5, and A6, independently, is a C1-C6 bivalent aliphatic radical; B1 is a C1-C6 bivalent aliphatic radical, a C1-C6 bivalent heteroaliphatic radical, a bivalent aryl radical, or a bivalent heteroaryl radical; B2 is a bond, a C1-C6 bivalent aliphatic radical, a C1-C6 bivalent heteroaliphatic radical, a bivalent aryl radical, a bivalent heteroaryl radical, D1-NR1—C(O)-D2, D1-C(O)NR1-D2-NR1′—C(O)-D3, D1-D2-C(O)—NR1—C(O)-D3, or D1-D2-D3, each of D1, D2, D3, independently, being a C1-C6 bivalent aliphatic radical, a C1-C6 bivalent heteroaliphatic radical, a bivalent aryl radical, a bivalent heteroaryl radical, a C1-C10 bivalent aralkyl radical, or a C1-C10 bivalent heteroaralkyl radical, and each of R1 and R1′, independently, being H, a C1-C6 bivalent heteroaliphatic radical, a bivalent aryl radical, a bivalent heteroaryl radical, or a C1-C10 bivalent aralkyl radical; each of L1 and L2, independently, is a bond, NR2, NR2C(O), NR2C(S), NR2CR3R4, NR2SO2, NR2C(O)NR3, or NR2C(S)NR3, each of R2, R3, and R4, independently, being H, a C1-C6 monovalent aliphatic radical, a C1-C6 monovalent heteroaliphatic radical, a monovalent aryl radical, a monovalent heteroaryl radical, a C1-C14 monovalent aralkyl radical, a C1-C14 monovalent heteroaralkyl radical, C(s)R′, or C(O)R′, in which R′ is a C1-C6 monovalent aliphatic radical, a C1-C6 monovalent heteroaliphatic radical, a monovalent aryl radical, a monovalent heteroaryl radical, a C1-C14 monovalent aralkyl radical, or a C1-C14 monovalent heteroaralkyl radical, provided that at least one of L1 and L2 is not a bond; each of W1, W2, W3, W4, W5, W6, W7, and W8, independently, is N or CR5, R5 being H, halo, cyano, amino, hydroxyl, nitro, sulfhydryl, a C1-C6 aliphatic radical, a C1-C6 heteroaliphatic radical, or a haloaliphatic radical; X is a bond, O, S, or NR6, R6 being H, a C1-C6 monovalent aliphatic radical, a C1-C6 monovalent heteroaliphatic radical, a monovalent aryl radical, a monovalent heteroaryl radical, a C1-C14 monovalent aralkyl radical, or a C1-C14 monovalent heteroaralkyl radical; Y is a aryl ring or a heteroaryl ring; and Z is an anticancer therapeutic moiety,wherein each of the aliphatic radical, the heteroaliphatic radical, the aralkyl radical, and the heteroaralkyl radical is unsubstituted or substituted with halo, cyano, amino, hydroxyl, nitro, sulfhydryl, C1-C6 alkoxy, C1-C6 alkylamino, C1-C12 dialkylamino, and C1-C6 haloalkyl; and each of the aryl radical and the heteroaryl radical is unsubstituted or substituted with halo, cyano, amino, hydroxyl, nitro, sulfhydryl, a C1-C6 aliphatic radical, a C1-C6 heteroaliphatic radical, or a haloaliphatic radical.