Hydrophilic linkers and ligand-drug conjugates thereof

A compound of Formula (1):

• UX—V—YnW (Formula 1)
• wherein:
• V represents a polar or charged group selected from the group consisting of
• (phosphonates),
• (phosphonic acids),
• (phosphoramidic acids),
• (phosphorodiamidic acids), and
• (phosphoric triamides), wherein R is H or C1˜C8 alkyl;
• Q is CH or N;
• Z is NH, NH—(CH2)m, or N(CH3)(CH2)m, wherein m is an integer from 1 to 5, and “” is a site of attachment;
• U represents a reactive functional group that enables a covalent linkage of the compound of Formula (1) with a cytotoxic drug and is selected from the group consisting of thiol group, disulfide groups, amino groups, carboxyl groups, aldehyde groups, ketone groups, maleimide groups, haloacetyl groups, alkenyl groups, alkynyl groups, hydrazine groups, and hydroxyl group;
• W represents a reactive functional group that enables a covalent linkage of the compound of Formula (1) with a cell-binding ligand, and is selected from the group consisting of N-hydroxysuccinmide ester group, N-sulfosuccinimidyl ester group, nitrophenyl ester group, dinitrophenyl ester group, pentafluorophenyl ester group, tetrafluorophenyl ester group, acyl chloride group, anhydride groups, sulfonyl chloride group, chloroformate group, isocyanate group, isothiocyanate group, aldehyde groups, ketone groups, disulfide groups, maleimide groups, acyl chloride group, haloacetyl groups, alkenyl pyridine groups, isocyanate group, and isothiocyanate group;
• X represents a component composed of one, two, or three methylene units optionally substituted with an alkyl, halo, hydroxyl, or alkoxy group;
• Y represents a component composed of one, two, or three methylene units optionally substituted with an alkyl, halo, hydroxyl, or alkoxy group;
• n is an integer from 1 to 100, provided that when n>1, values of each V, X, and Y in the repeating brackets of Formula (1) are independent and do not have to be identical.

A compound of Formula (1):

• UX—V—YnW (Formula 1)
• wherein:
• V represents
• wherein R is C1˜C8 alkyl;
• and “” is a site of attachment;
• U represents a reactive functional group that enables a covalent linkage of the compound of Formula (1) with a cytotoxic drug and is selected from the group consisting of thiol group, disulfide groups, amino groups, aldehyde groups, ketone groups, maleimide groups, haloacetyl groups, alkenyl groups, alkynyl groups, hydrazine groups, and hydroxyl group:
• W represents a reactive functional group that enables a covalent linkage of the compound of Formula (1) with a cell-binding ligand, and is selected from the group consisting of N-hydroxysuccinmide ester group, N-sulfosuccinimidyl ester group, nitrophenyl ester group, dinitrophenyl ester group, pentafluorophenyl ester group, tetrafluorophenyl ester group, acyl chloride group, anhydride groups, sulfonyl chloride group, chloroformate group, isocyanate group, isothiocyanate group, aldehyde groups, ketone groups, disulfide groups, maleimide groups, acyl chloride group, haloacetyl groups, alkenyl pyridine groups, isocyanate group, and isothiocyanate group;
• X represents a component composed of one, two, or three methylene units optionally substituted with an alkyl, halo, hydroxyl, or alkoxy group;
• Y represents a component composed of one, two, or three methylene units optionally substituted with an alkyl, halo, hydroxyl, or alkoxy group;
• n is an integer from 1 to 100, provided that when n>1, values of each V, X, and Y in the repeating brackets of Formula (1) are independent and do not have to be identical.