| 主权项 |
1. A prodrug or a pharmaceutically acceptable salt thereof comprising:
a drug linker conjugate D-L; wherein D is a biologically active moiety containing an aromatic hydroxyl group; and wherein L is a non-biologically active linker having a first and a second amine group, wherein:
the first amine group is a primary, secondary, or tertiary amine, or a quaternary ammonium cation; andL is connected to D through a carbamate bond connecting the second amine group and the aromatic hydroxyl group of D; wherein L comprises:
i) a moiety L1 of formula (I); wherein the dashed line indicates the attachment of L1 to the aromatic hydroxyl group of D by forming a carbamate group;wherein R1 is selected from the group consisting of:
C1-4 alkyl;heteroalkyl;C3-7 cycloalkyl; and wherein R2, R2a, R3, and R3a are independently selected from hydrogen, substituted or non-substituted linear, branched or cyclic C1-4 alkyl, and heteroalkyl; andwherein m is independently 2, 3 or 4; andii) a moiety L2, which is a chemical bond or a spacer, wherein:
L2 is bound to a carrier group Z; andZ is a polymer with a molecular weight ≧500 g/mol selected from the group consisting of:
2-methacryloyl-oxyethyl phosphoyl cholins, hydrogels, PEG based hydrogels, poly(acrylic acids), poly(acrylates), poly(acrylamides), poly(alkyloxy) polymers, poly(amides), poly(amidoamines), poly(amino acids), poly(anhydrides), poly(aspartamides), poly(butyric acids), poly(glycolic acids), polybutylene terephthalates, poly(caprolactones), poly(carbonates), poly(cyanoacrylates), poly(dimethylacrylamides), poly(esters), poly(ethylenes), poly(ethyleneglycols), poly(ethylene oxides), poly(ethyl phosphates), poly(ethyloxazolines), poly(glycolic acids), poly(hydroxyethyl acrylates), poly(hydroxyethyloxazolines), poly(hydroxymethacrylates), poly(hydroxypropylmethacrylamides), poly(hydroxypropyl methacrylates), poly(hydroxypropyloxazolines), poly(iminocarbonates), poly(lactic acids), poly(lactic-co-glycolic acids), poly(methacrylamides), poly(methacrylates), poly(methyloxazolines), poly(organophosphazenes), poly(ortho esters), poly(oxazolines), poly(propylene glycols), poly(siloxanes), poly(urethanes), poly(vinyl alcohols), poly(vinyl amines), poly(vinylmethylethers), poly(vinylpyrrolidones), silicones, celluloses, carbomethyl celluloses, hydroxypropyl methylcelluloses, chitins, chitosans, dextrans, dextrins, gelatins, hyaluronic acids and derivatives, mannans, pectins, rhamnogalacturonans, starches, hydroxyalkyl starches, hydroxyethyl starches and other carbohydrate-based polymers, xylans, and copolymers thereof;wherein L1 is substituted with one to four L2 moieties, by replacing any one to four hydrogen(s) of L1 with a moiety L2; and wherein optionally, L is further substituted. |
