Glucose-sensitive albumin-binding derivatives

A diboron conjugate represented by the general Formula I′

• R1′—X′—R2′
• in which Formula I′,
• X′ represents a linker of Formula Ia′:
• wherein
• ---- represents a covalent bond towards R1′ or R2′;
• D represents a drug substance;
• and
• W′ represents a covalent bond, or a linker selected from the group consisting of —NHCH2(C═O)—, —NHCH2CH2(C═O)—, —NHCH2CH2CH2(C═O)—, and —NHCH(COOH)CH2CH2(C═O)— (the latter representing an L-gamma-Glu or a D-gamma-Glu residue);
• or
• X′ represents a linker of Formula Ib′:
• wherein,
• ---- represents a covalent bond towards R1′ or R2′;
• and
• R3′ represent —(CH2)m′(C═O)—W′-D, wherein
• m′ represents an integer in the range of 1 to 4;
• W′ represents a covalent bond or a linker selected from the group consisting of —NHCH2(C═O)—, —NHCH2CH2(C═O)—, —NHCH2CH2CH2(C═O)—, and —NHCH(COOH)CH2CH2(C═O)— (the latter representing an L-gamma-Glu or a D-gamma-Glu residue);
• and
• D represents a drug substance;
• or
• X′ represents a linker of Formula Ic′:
• which represents a D- or an L-amino acid form;
• and
• wherein,
• ---- represents a covalent bond towards R1′ or R2′;
• n′ represents an integer in the range of 1 to 4;
• W′ represents a covalent bond or a linker selected from the group consisting of —NHCH2(C═O)—, —NHCH2CH2(C═O)—, —NHCH2CH2CH2(C═O)—, and —NHCH(COOH)CH2CH2(C═O)— (the latter representing an L-gamma-Glu or a D-gamma-Glu residue);
• and
• D represents a drug substance;
• or
• X′ represents a linker of Formula Id′:
• which represents a R,R or S,S, or R,S or R,S stereoisomer of the 3,4-diamino-pyrrolidine;
• wherein,
• ---- represents a covalent bond towards R1′ or R2′;
• R4′ represents —(C═O)(CH2)p′(C═O)—W′-D;
• where
• W′ represents a covalent bond or a linker selected from the group consisting of —NHCH2(C═O)—, —NHCH2CH2(C═O)—, —NHCH2CH2CH2(C═O)—, and —NHCH(COOH)CH2CH2(C═O)— (the latter representing an L-gamma-Glu or a D-gamma-Glu residue);
• wherein p′ represents an integer in the range of 1 to 4;
• and
• D represents a drug substance;
• or
• X′ represents a linker of Formula Ie′:
• wherein,
• --- represents a covalent bond towards R1′ or R2′;
• or
• X′ represents a linker of Formula If′:
• wherein,
• ---- represents a covalent bond towards R1′ or R2′;
• or
• X′ represents a linker of Formula Ig′:
• wherein,
• --- represents a covalent bond towards R1′ or R2′;
• or
• X′ represents a linker of Formula Ih′:
• wherein,
• --- represents a covalent bond towards R1′ or R2′;
• or
• X′ represents a linker of Formula Ii′:
• wherein,
• ---- represents a covalent bond towards R1′ or R2′;
• and
• W′ represents a covalent bond or a linker selected from the group consisting of —NHCH2(C═O)—, —NHCH2CH2(C═O)—, —NHCH2CH2CH2(C═O)—, and —NHCH(COOH)CH2CH2(C═O)— (the latter representing an L-gamma-Glu or a D-gamma-Glu residue);
• and
• R1′ and R2′, which may be identical or different, each represents a group of Formula IIa′ or Formula IIb′:
• wherein,
• one to four Y′ represents H;
• and
• none, one or two Y′ represents F, Cl, CF2, CF3, SF5, OCF3, SO2CH3 and/or SO2CF3;
• and
• one Y′ represents (a covalent bond representing) the attachment point to X′ of Formula I′;
• and
• when X′ is Formula Ie′, If′, Ig′ or Ih′, one Y in either R1′ or R2′ represents —(C═O)—W′-D, where W′ represents a covalent bond, or a linker selected from the group consisting of —NHCH2(C═O)—, —NHCH2CH2(C═O)—, —NHCH2CH2CH2(C═O)—, and —NHCH(COOH)CH2CH2(C═O)— (the latter representing an L-gamma-Glu or a D-gamma-Glu residue);
• and
• wherein D represents a drug substance.