Ligand-drug-conjugate comprising a single molecular weight polysarcosine

An intermediate compound having formula (XVI)

• wherein
• L is an orthogonal connector,
• HPSMW results from covalent binding to said orthogonal connector L, of a single molecular weight homopolymer having formula (I)
• wherein
• R1 and R2 are different, and
• one of R1 and R2 is H or an inert group, the other one of R1 and R2 being a functionalized reactive group, said group being reactive for covalently binding a bindable group, in such reaction conditions that the inert group is non-reactive,
• Z1 and Z2, identical or different, are optional spacers, and
• n is 1 or more and k is 2 or more;
• D is a cytotoxic drug,
• X is an optional cleavable moiety for releasing D,
• Z is an optional spacer, and
• a is 1 or more and b is 0, 1 or more.

A compound having formula (XXIII)

• wherein
• R6 is —C1-C10 alkylene-, —C1-C10 heteroalkylene-, —C3-C8 carbocyclo-, —O—(C1 C8 alkyl)-, -arylene-, —C1-C10 alkylene-arylene-, -arylene-C1-C10 alkylene-, —C1-C10 alkylene-(C3-C8 carbocyclo)-, —(C3-C8 carbocyclo)-C1-C10 alkylene-, —C3-C8 heterocyclo-, —C1-C10 alkylene-(C3-C8 heterocyclo)-, —(C3-C8 heterocyclo)-C1-C10 alkylene-, —C1-C10 alkylene-C(═O)—, —C1-C10 heteroalkylene-C(═O)—, —C3-C8 carbocyclo-C(═O)—, —O—(C1-C8 alkyl)-C(═O)—, -arylene-C(═O)—, —C1-C10 alkylene-arylene-C(═O)—, -arylene-C1-C10 alkylene-C(═O)—, —C1-C10 alkylene-(C3-C8carbocyclo)-C(═O)—, —(C3-C8 carbocyclo)-C1-C10 alkylene-C(═O)—, —C3-C8 heterocyclo-C(═O)—, —C1-C10 alkylene-(C3-C8 heterocyclo)-C(═O)—, —(C3-C8 heterocyclo)-C1-C10 alkylene-C(═O)—, —C1-C10 alkylene-NH—, —C1-C10 heteroalkylene-NH—, —C3-C8 carbocyclo-NH—, —O—(C1-C8 alkyl)-NH—, -arylene-NH—, —C1-C10 alkylene-arylene-NH—, -arylene-C1-C10 alkylene-NH—, —C1-C10 alkylene-(C3-C8 carbocyclo)-NH—, —(C3-C8 carbocyclo)-C1-C10 alkylene-NH—, —C3-C8heterocyclo-NH—, —C1-C10 alkylene-(C3-C8 heterocyclo)-NH—, —(C3-C8 heterocycle)-C1-C10 alkylene-NH—, —C1-C10 alkylene-S—, —C1-C10 heteroalkylene-S—, —C3-C8carbocyclo-S—, —O—(C1-C8 alkyl)-)—S—, -arylene-S—, —C1-C10 alkylene-arylene-S—, -arylene-C1-C10 alkylene-S—, —C1-C10 alkylene-(C3-C8 carbocyclo)-S—, —(C3-C8 carbocyclo)-C1-C10 alkylene-S—, —C3-C8 heterocyclo-S—, —C1-C10 alkylene-(C3-C8 heterocyclo)-S—, —(C3-C8 heterocyclo)-C1-C10 alkylene-S—, —C1-C10 alkylene-O—C(═O)—, —C3-C8 carbocyclo-O—C(═O)—, —O—(C1-C8 alkyl)-O—C(═O)—, -arylene-O—C(═O)—, —C1-C10 alkylene-arylene-O—C(═O)—, -arylene-C1-C10 alkylene-O—C(═O)—, —C1-C10 alkylene-(C3-C8carbocyclo)-O—C(═O)—, —(C3-C8 carbocyclo)-C1-C10 alkylene-O—C(═O)—, —C3-C8 heterocyclo-O—C(═O)—, —C1-C10 alkylene-(C3-C8heterocyclo)-O—C(═O)—, —(C3-C8 heterocyclo)-C1-C10 alkylene-O—C(═O)—,
• any of the R6 group is optionally substituted with one or more of the substituents selected from:
• —X, —R′, —O−, —OR′, ═O, —SR′, —S, —NR′2, —NR′3+, ═NR′, —CX3, —CN, —OCN, —SCN, —N═C═O, —NCS, —NO, —NO2, ═N2, —N3, —NR′C(═O)R′, —C(═O)R′, —C(═O)NR′2, —SO3−, —SO3H, —S(═O)2R′, —OS(═O)2OR′, —S(═O)2NR′, —S(═O)R′, —OP(═O)(OR′)2, —P(═O)(OR′)2, —PO3−, —PO3H2, —C(═O)X, —C(═S)R′, —CO2R′, —CO2, —C(═S)OR′, C(═O)SR′, C(═S)SR′, C(═O)NR′2, C(═S)NR′2, and C(═NR′)NR′2, where each X is independently a halogen:
• —F, —Cl, —Br, or —I;
• and each R′ is independently —H, —C1C20 alkyl, —C6-C20 aryl, or —C3-C14 heterocycle,
• Z is an optional spacer,
• L is an orthogonal connector,
• X is an optional cleavable moiety for releasing D,
• D is a cytotoxic drug,
• a is 1 or more and b is 0, 1 or more, and
• HPSMW results from covalent binding to said orthogonal connector L, of a single molecular weight homopolymer having formula (I)
• wherein
• R1 and R2 are different, and
• one of R1 and R2 is H or an inert group, the other one of R1 and R2 being a functionalized reactive group, said group being reactive for covalently binding a bindable group, in such reaction conditions that the inert group is non-reactive,
• Z1 and Z2, identical or different, are optional spacers, and
• n is 1 or more and k is 2 or more.