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

Claim 13:
14. The Ligand-Drug Conjugate compound of claim 10, wherein A or a subunit thereof is -LP(PEG)-, wherein -LP- or a subunit thereof has the structure of Formula LP-1 or LP-2:, or a salt thereof, wherein
XLP is selected from the group consisting of —O—, —NRLP—, —S—, —S(═O)—, —S(═O)2—, —C(═O)—, —C(═O)N(RLP)—, —N(RLP)C(═O)N(RLP)—, —N(RLP)C(═NRLP)N(RLP)—, and C3-C8 heterocyclo;
wherein each RLP is independently selected from the group consisting of hydrogen and optionally substituted C1-C6 alkyl, or two of RLP together along with the carbons atoms to which they are attached and their intervening atoms define a C5-C6 heterocyclo and any remaining RLP are as previously defined;
Ar is an optionally substituted C6-C10 arylene or an optionally substituted C5-C10 heteroarylene;
each RE and RF is independently selected from the group consisting of —H, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkylene, optionally substituted C6-C10 arylene, and optionally substituted C5-C10 heteroarylene,
or RE and RF together with the carbon atom to which both are attached defines an optionally substituted spiro C3-C6 carbocyclo, or RE and RF from adjacent carbon atoms together with these atoms and any intervening carbon atoms defines an optionally substituted C5-C6 carbocyclo with any remaining RE and RF as previously defined; and
wherein one of the wavy lines indicates the site of covalent attachment of a PEG Unit and the other wavy line indicates covalent attachment of Formula LP-1 or Formula LP-2 within the structure representing the Ligand Drug Conjugate composition,
or wherein -LP(PEG)- has the structure of Formula LP-3 or Formula LP-4:, or a salt thereof, wherein
subscript v is an integer ranging from 1 to 4;
XLP is selected from the group consisting of —O—, —NRLP—, —S—, —S(═O)—, —S(═O)2—, —C(═O)—, —C(═O)N(RLP)—, —N(RLP)C(═O)N(RLP)—, —N(RLP)C(═NRLP)N(RLP)—, and C3-C8 heterocyclo, or XLP is selected from the group consisting of —O—, —NH, —S— and —C(═O)—;
wherein each RLP is independently selected from the group consisting of hydrogen and optionally substituted C1-C6 alkyl, or two of RLP together along with the carbons atoms to which they are attached and their intervening atoms define a C5-C6 heterocyclo and any remaining RLP are as previously defined;
Ar is an optionally substituted C6-C10 arylene or an optionally substituted C5-C10 heteroarylene;
each RE and RF is independently selected from the group consisting of —H, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkylene, optionally substituted C6-C10 arylene, and optionally substituted C5-C10 heteroarylene, or RE and RF are independently selected from the group consisting of —H and —C1-C4 alkyl,
or RE and RF together with the carbon atom to which both are attached defines an optionally substituted spiro C3-C6 carbocyclo, or RE and RF from adjacent carbon atoms together with these atoms and any intervening carbon atoms defines an optionally substituted C5-C6 carbocyclo with any remaining RE and RF as previously defined, or wherein the side chain of —[C(RE)(RF)]v—XLP— is provided by a natural or un-natural amino acid side chain; and
wherein one of the wavy lines indicate the site of covalent attachment of a PEG Unit and the other line indicates covalent attachment of Formula LP-1 or Formula LP-2 within the structure representing the Ligand Drug Conjugate composition,
and wherein PEG in LP-3 or LP-4 has the structure selected from the group consisting of:, wherein the wavy line indicates site of covalent attachment to XLP of the Parallel Connector Unit (LP);
subscript n′ independently ranges from 1 to 72;
RPEG1 is an optional PEG Attachment Unit;
RPEG2 is a PEG Capping Unit; and
RPEG3 is a PEG Coupling Unit,, or
wherein XLP-PEG in LP-3 has the structure of:, wherein subscript n′ is 8, 12, or 24 and RPEG2 is H or —CH3,
or A or a subunit thereof has the structure of formula (3) or formula (4):, wherein the wavy lines indicated covalent attachment within the compound structure;
wherein K and L′ independently are C, N, O, or S, provided that when K or L′ is O or S, R41 and R42 to K or R43 and R44 to L′ are absent, and when K or L′ are N, one of R41, R42 to K or one of R42, R43 to L′ are absent, and provided that no two adjacent L′ are independently selected as N, O, or S;
wherein subscripts e and f are independently selected integers that range from 0 to 12, and subscript g is an integer ranging from 1 to 12;
wherein G is hydrogen, optionally substituted C1-C6 alkyl, —OH, —ORPR, or —CO2H, CO2RPR, wherein RPR is a suitable protecting, or
G is —N(RPR)(RPR), wherein RPR are independently a protecting group or RPR together form a suitable protecting group, or
G is —N(R45)(R46), wherein one of R45, R46 is hydrogen or RPR, wherein RPR is a suitable protecting group, and the other is hydrogen or optionally substituted C1-C6 alkyl;
wherein R38 is hydrogen or optionally substituted C1-C6 alkyl;
R39-R44 are independently selected from the group consisting of hydrogen, optionally substituted C1-C6 alkyl, optionally substituted aryl, and optionally substituted heteroaryl, or
R39 and R40 together with the carbon atom to which both are attached, or R41, R42 together with K to which both are attached when K is a carbon atom, define a C3-C6 carbocyclo, and R41-R44 are as defined herein,
or R43, R44 together with L′ to which both are attached when L′ is a carbon atom define a C3-C6 carbocyclo, and R39-R42 are as defined herein,
or R40 and R41, or R40 and R43, or R41 and R43 together with the carbon atom or heteroatom to which both are attached and the atoms intervening between those carbon atoms and/or heteroatoms define a C5-C6 carbocyclo or a C5-C6 heterocyclo, and R39, R44 and the remainder of R40-R43 are as defined herein,
provided that when K is O or S, R41 and R42 are absent, and when K is N, one of R41 and R42 is absent, and when L′ is O or S, R43 and R44 are absent, and when L′ is N, one of R43, R44 is absent,
or A or a subunit thereof has the structure of formula (3a) or formula (4a):, wherein subscript e and f are independently 0 or 1,
or A, or a subunit thereof, is an alpha-amino, beta-amino, or another amine-containing acid residue.