| abstract |
A hydrophilic linker of formula (I). ** Formula ** in which: Y represents a functional group that allows reaction with a cell binding agent; Q and T are -P (= O) (OM) -, or -S (O2) -, or -S (O) -; m and n are integers from 0 to 5, but not 0 at the same time; Furthermore, when m = 1, n = 0, Q is not -P (= O) (OM) -; or when n = 1, m = 0, T is not -P (= O) (OM) -; Z represents a functional group that allows the binding of a cytotoxic drug through a disulfide, thioether, thioester, peptide, hydrazone, ether, ester, carbamate, carbonate, amine (secondary, tertiary or quaternary), imine, cycloheteroalkylene, heteroaromatic , alkoxime or amide, said functional group Z being selected from thiol, disulfide, amino, carboxy, aldehydes, maleimido, haloacetyl, hydrazines and hydroxy; R1, R2, R3, R4, R5 and R6 are the same or different and are H, linear alkyl having 1 to 6 carbon atoms, branched or cyclic alkyl having 3 to 6 carbon atoms, alkenyl or linear alkynyl, branched or cyclic, or 1-6 carbon atoms of the polyethylene oxide esters, ether, amide or unit of formula (OCH2CH2) p, where p is an integer from 0 to 1,000, or a combination thereof; or R1, R2, R3 and R4 are respectively a chain of atoms selected from C, N, O, S, Si and P that covalently connect the binding ligand to the cell surface, the phosphinate or sulfonyl group, the conjugated drug and between themselves (R1, R2, R3 and R4), wherein said atoms combine in any chemically relevant way, such as by the formation of alkylene, alkenylene and alkynylene, ethers, polyoxyalkylene, esters, amines, imines, polyamines, hydrazines, hydrazones, amides, ureas, semicarbazides, carbazides, alkoxyamines, alkoxylamines, urethanes, amino acids, peptides, acyloxylamines, hydroxamic acids, or a combination thereof; M is H, or Na, or K, or N + R1R2R3 or a pharmaceutical salt, where R1, R2, and R3 were described above. |