Bio-orthogonal drug activation

A compound, including salts, hydrates, or solvates thereof, wherein said compound comprises a substituted eight-membered non-aromatic cyclic mono-alkenylene moiety linked to a drug;

• wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety optionally comprises one or more heteroatoms;
• wherein the substituted eight-membered non-aromatic cyclic mono-alkenylene moiety comprises at least one allylic carbon;
• wherein the at least one allylic carbon of the eight-membered non-aromatic cyclic mono-alkenylene moiety is directly linked to a cleavable bond,
• wherein the cleavable bond comprises at least one S, N, NH, or O;
• wherein the cleavable bond is selected from the group consisting of carbamate, thiocarbamate, carbonate, thiocarbonate, ether, ester, amine, amide, thioether, thioester, sulfoxide, and sulfonamide bonds;
• wherein the at least one S, N, NH, or O of the cleavable bond is part of the drug, or part of an optional linker between the cleavable bond and the drug;
• and
• wherein optionally one or more targeting agents or masking moieties are attached to the drug, the eight-membered non-aromatic cyclic mono-alkenylene moiety, or the optional linker, optionally via a spacer or spacers.

A method of administering a drug to a patient suffering from a disease that can be modulated by the drug, the method comprising administering to the patient a compound or a salt, hydrate, or solvate thereof, and administering to the patient an activator or a salt, hydrate, or solvate thereof,

• wherein said compound comprises a substituted eight-membered non-aromatic cyclic mono-alkenylene moiety linked to a drug;
• wherein said eight-membered non-aromatic cyclic mono-alkenylene moiety optionally comprises one or more heteroatoms;
• wherein the substituted eight-membered non-aromatic cyclic mono-alkenylene moiety comprises at least one allylic carbon;
• wherein the at least one allylic carbon of the eight-membered non-aromatic cyclic mono-alkenylene moiety is directly linked to a cleavable bond,
• wherein the cleavable bond comprises at least one S, N, NH, or O;
• wherein the cleavable bond is selected from the group consisting of carbamate, thiocarbamate, carbonate, thiocarbonate, ether, ester, amine, amide, thioether, thioester, sulfoxide, and sulfonamide bonds;
• wherein the at least one S, N, NH, or O of the cleavable bond is part of the drug, or part of an optional linker between the cleavable bond and the drug;
• and
• wherein optionally one or more targeting agents or masking moieties are attached to the drug, the eight-membered non-aromatic cyclic mono-alkenylene moiety, or the optional linker, optionally via a spacer or spacers;
• and wherein the activator has Formula 4
• wherein R1 and R2 each independently are selected from the group consisting of H, alkyl, aryl, NR′C(═O)R″, NR′C(═S)R″, NR′C(═O)OR″, NR′C(═S)OR″, NR′C(═O)SR″, NR′C(═S)SR″, OC(═O)NR′R″, SC(═O)NR′R″, OC(═S)NR′R″, SC(═S)NR′R″, NR′C(═O)NR″R″, NR′C(═S)NR″R″ with each R′ and each R″ independently being H, aryl or alkyl, and R′″ independently being aryl or alkyl;
• wherein A is N;
• B is N;
• X is N;
• and Y is N;
• wherein neither or at least one of the substituents R1 and R2 on the diene is linked to a polymer, protein, peptide, carbohydrate, dendrimer, heparin derivative, hyaluronic acid derivative, albumin, albumin-binding moiety, dye moiety, fluorescent moiety, imaging probe, chelate, liposome, polymer particle or polymersome.