Conjugates for selective responsiveness to vicinal diols

A compound represented by Formula I:

• Z—R (Formula I)
• wherein, in Formula I,
• R is selected from Formulae FF1-FF24;
• and
• Z is selected from one of:
• a) NH2 or OH,
• b) a covalent linkage, either directly or via an optional linker, to a drug substance, wherein the drug substance is insulin, a polypeptide, Drug substance, or a human peptide hormone, and wherein the insulin comprising human insulin or an analog thereof comprising 2 to 10 amino acids that are each independently modified as described by Formula I
• c) a covalent linkage, either directly or via the optional linker, to an N-terminal amine or an epsilon amino group of one or more amino acids in a polypeptide drug substance, and
• d) a group represented by J—SCH2-ø, J—S(CH2)2—ø, J—NH—ø, J—NH—(the optional linker)-ø, J—S(CH2)kNH—ø, or J-triazole(CH2)kNH—ø;
• wherein —ø is the covalent bond towards R;
• index k is an integer in the range of 3 to 14;
• and
• J is an amino acid or one or more amino acids in a polypeptide drug substance, wherein each of the one or more amino acids in the polypeptide drug substance is represented by Formula I′:
• wherein, in Formula I′,
• indicate points of attachment to remaining portions of the polypeptide drug substance;
• * indicates the point of attachment to the remaining portion of Z;
• and
• index n is an integer in the range of 1 to 8,
• wherein for Formulae FF1-FF24:
• X represents a covalent linkage, either directly or via the optional linker, towards Z in Formula I;
• index i is an integer in the range of 1 to 20;
• B1 and B2 are identical or different, and each independently represent a group selected from Formulae F1-F9;
• and
• B3 represents a group selected from Formulae F1-F11,
• wherein, for each of Formulae F1-F9:
• one R1 represents (C═O)—, S(═O)(═O)—, (CH2)m(C═O)—, or (CH2)m—, wherein —represents a covalent bond to the remainder of R in Formula I;
• none, one, or two R1 each independently represent F, Cl, Br, OH, CH2—NH2, NH2, (C═O)—NH2, SO2CH3, CF3, NO2, CH3, OCH3, O(CH2)mCH3, —(SO2)NH CH3, —(SO2)NH(CH2)mCH3, or OCF3,
• index m is an integer in the range of 1 to 14;
• one R1 in F5 represents B(OH)2, and
• all remaining R1 represent H, and
• in Formula F10, index j is an integer in the range of 1 to 13.