| 主权项 |
1. A bridge linker compound of the Formula (I) Wherein: The acetylenedicarboxyl group on the linker is capable of reacting with a pair of sulfur atoms of the cell-binding agent; The sulfur atoms are preferred pairs of thiols reduced from the interchain disulfide bonds of the cell-binding agent by a reducing agent, such as DTT and/or TCEP; Z1 and Z2 are the same or different a function group that enables to react with a cytotoxic drug, to form a disulfide, thioether, thioester, peptide, hydrazone, ether, ester, carbamate, carbonate, amine (secondary, tertiary, or quarter), imine, cycloheteroalkyl, heteroaromatic, alkyloxime or amide bond; R1 and R2 are the same or different, and are absent, linear alkyl having from 1-6 carbon atoms, branched or cyclic alkyl having from 3 to 6 carbon atoms, linear, branched or cyclic alkenyl or alkynyl, or 1˜6 carbon atoms of esters, ether, amide, or polyethyleneoxy unit of formula (OCH2CH2)p, wherein p is an integer from 0 to about 1000, or combination thereof. Additionally R1 and R2 are respectively a chain of atoms selected from C, N, O, S, Si, and P, preferably having 0˜500 atoms, which covalently connects to X1 or X2 and Z1 or Z2. The atoms used in forming the R1 and R2 may be combined in all chemically relevant ways, such as forming alkylate, alkylene, alkenylene, and alkynylene, ethers, polyoxyalkylene, esters, amines, imines, polyamines, hydrazines, hydrazones, amides, ureas, semicarbazides, carbazides, alkoxyamines, alkoxyamines, urethanes, amino acids, peptides, acyloxylamines, hydroxamic acids, or combination thereof. X1 and X2 are independently selected from NH, N(R3), O, S or CH2; R3 is H, linear alkyl having from 1-6 carbon atoms, branched or cyclic alkyl having from 3 to 6 carbon atoms, linear, branched or cyclic alkenyl or alkynyl, or 1˜6 carbon atoms of esters, ether, amide, or polyethyleneoxy unit of formula (OCH2CH2)p, wherein p is an integer from 0 to about 1000, or combination thereof. |
