Patent ID: 11931414
Assignee: SEAGEN INC.
Field: Pharmaceuticals (Chemistry)
Classification: CPC A  C | IPC A  C

Claim 9:
10. The Ligand Drug Conjugate compound of claim 9, wherein the compound is represented by the structure of Formula 1a or Formula 1b or is represented by the structure of Formula 1c or Formula 1d:, or a salt thereof, wherein
S is a sulfur atom of the Ligand Unit which is an antibody or an antigen-binding fragment thereof, which in Formula 1b or Formula 1d is bonded to the carbon atom α or β to the carboxylic acid functional group of the indicated succinic acid amide (M3) moiety;
R6 is hydrogen or an optionally substituted C1-C6 alkyl, which in Formula 1b or Formula 1d is bonded to the saturated carbon atom adjacent to the carbon atom substituted by L-S—;
or
wherein the compound is represented by the structure of Formula 1a′ or Formula 1b′:, or a salt thereof, wherein
S is a sulfur atom of the Ligand Unit which is an antibody or an antigen-binding fragment thereof, which in Formula 1b′ or Formula 1d′ is bonded to the carbon atom α or β to the carboxylic acid functional group of the indicated succinic acid amide (M3) moiety
[HE] is an optional Hydrolysis Enhancing Unit;
W is a Peptide Cleavable Unit, and Y is the self-immolative Spacer Unit and comprises a PAB or PAB-type moiety,
wherein the remaining variable groups are as previously described for Formula 1a′ and Formula 1b′,, or
W—Y is replaced by a Glucuronide Unit of formula —Y(W′)— having the structure of:, or a salt thereof, wherein Su is the carbohydrate moiety with glycosidic bonding to Y through an optionally substituted heteroatom represented by -E′ so that Su-E′ is W′ and the remainder of the Glucuronide Unit structure is the self-immolative Spacer Unit (Y) bonded to W′;
J′ is an independently selected optionally substituted heteroatom;
V, Z1, Z2 and Z3 are selected from the group consisting of ═N— and ═C(R24)—, wherein each R24 is selected from the group consisting of hydrogen and optionally substituted C1-C12 alkyl, optionally substituted C2-C12 alkenyl, optionally substituted C2-C12 alkynyl, halogen, an electron withdrawing group, an electron donating group, -E′-Su, and —C(R8)(R9)—,
provided that one and only one —C(R8)(R9)— moiety and one and only one -E′-Su moiety is present, and
one of V, Z1, Z2 and Z3 is ═C(R24)— in which R24 is —C(R8)(R9)— and another of V, Z1, Z2 and Z3 is ═C(R24)— in which R24 is -E′-Su, and
provided the —C(R8)(R9)— and -E′-Su moieties are ortho or para to each other;
one of R8 and R9 is hydrogen and the other is hydrogen, optionally substituted C1-C12 alkyl, optionally substituted C2-C12 alkenyl, optionally substituted C2-C12 alkynyl, optionally substituted C6-C20 aryl, or optionally substituted C5-C20 heteroaryl; and
R′ is hydrogen, —NO2, or an electron withdrawing group; and
wherein the wavy line adjacent to J′ indicates the site of covalent attachment of the Glucuronide Unit to A when subscript a is 1 or to the indicated LSS or LS primary linker when subscript a is 0; and the wavy line adjacent to the —C(R8)(R9)— moiety indicates the site of covalent attachment of the Glucuronide Unit to D+; and
wherein glycosidase action on the Glucuronide Unit resulting in cleavage of its glycosidic bond initiates release of the quaternized NAMPT Drug (D+) Unit as NAMPTi compound from a drug linker moiety of the Ligand Drug Conjugate compound; and the remaining variable groups are as previously described for Formula 1a′ and Formula 1b′;
or wherein the compound is represented by the structure of Formula 1c′ or Formula 1d′:, or a salt thereof,
wherein [HE] is an optional Hydrolysis Enhancing Unit; and
W is Peptide Cleavable Unit, and Y is the self-immolative Spacer Unit (Y) and comprises a PAB or PAB-type moiety,
W—Y is replaced by a Glucuronide Unit of formula —Y(W′)— having the structure of:, or a salt thereof, wherein
Su is the carbohydrate moiety with glycosidic bonding to Y through an optionally substituted heteroatom represented by -E′ so that Su-E′ is W′ and the remainder of the Glucuronide Unit structure is the self-immolative Spacer Unit (Y) bonded to W′;
J′ is an independently selected optionally substituted heteroatom;
V, Z1, Z2 and Z3 are selected from the group consisting of ═N— and ═C(R24)—, wherein each R24 is selected from the group consisting of hydrogen, optionally substituted C1-C12 alkyl, optionally substituted C2-C12 alkenyl, optionally substituted C2-C12 alkynyl, halogen, an electron withdrawing group, an electron donating group, -E′-Su, and —C(R8)(R9)—,
provided that one and only one —C(R8)(R9)— moiety and one and only one -E′-Su moiety is present, and
one of V, Z1, Z2 and Z3 is ═C(R24)— in which R24 is —C(R8)(R9)— and another of V, Z1, Z2 and Z3 is ═C(R24)— in which R24 is -E′-Su,
provided the —C(R8)(R9)— and -E′-Su moieties are ortho or para to each other;
one of R8 and R9 is hydrogen and the other is hydrogen, optionally substituted C1-C12 alkyl, optionally substituted C2-C12 alkenyl, optionally substituted C2-C12 alkynyl, optionally substituted C6-C20 aryl, or optionally substituted C5-C20 heteroaryl;, and
R′ is hydrogen, —NO2, or an electron withdrawing group; and
wherein the wavy line adjacent to J′ indicates the site of covalent attachment of the Glucuronide Unit to A when subscript a is 1 or to the indicated LSS or LS primary linker when subscript a is 0; and the wavy line adjacent to the —C(R8)(R9)— moiety indicates the site of covalent attachment of the Glucuronide Unit D+; and
wherein glycosidase action on the Glucuronide Unit resulting in cleavage of its glycosidic bond initiates release of the quaternized NAMPT Drug (D+) Unit as a NAMPTi compound from a drug linker moiety of the Ligand Drug Conjugate compound.