Patent ID: 11857565
Assignee: SEAGEN INC.
Field: Pharmaceuticals (Chemistry)
Classification: CPC C  A | IPC A

Claim 6:
7. The Ligand Drug Conjugate composition of claim 1, wherein its drug linker moieties are represented by the structure(s) of:, or a salt thereof, wherein HE is an optional Hydrolysis Enhancing Unit;
AO is absent or is a second subunit of A;
A′ is a second optional Stretcher Unit;
subscript a′ is 0 or 1, indicating the absence or presence of A′, respectively;
subscript P is 1 or 2;
subscript Q ranges from 1 to 6;
Ra3 is —H, optionally substituted C1-C6 alkyl, optionally substituted —C1-C4 alkylene-(C6-C10 aryl), or —RPEG1—O—(CH2CH2O)1-36—RPEG2, wherein RPEG1 is C1-C4 alkylene, RPEG2 is —H or C1-C4 alkylene,
wherein the basic nitrogen bonded to Ra3 is optionally protonated or is in a salt form,
R34 is —CH3, —C(CH3)2, —CH2COOH, —CH2CH2COOH or —CH2CH2CH2CH2NH2;and
R35 is methyl, isopropyl, —CH2C(═O)NH2, —CH2COOH, —CH2CH2C(═O)NH2, —CH2CH2COOH, —CH2CH2CH2NHC(═NH)NH2, —CH2CH2CH2NH2, —CH2CH2CH2NH—C(═O)CH3, —CH2CH2CH2NH—C(═O)H, —CH2CH2CH2CH2NHC(═NH)NH2, —CH2CH2CH2CH2NH2—, —CH2CH2CH2CH2NH—C(═O)CH3, —CH2CH2CH2CH2NH—C(═O)H, —CH2CH2CH2NHC(═O)NH2, —CH2CH2CH2CH2NHC(═O)NH2 or —CH2CH2CH(OH)CH2NH2;
R2 is methyl; and
R1 is C1-C9 alkyl, optionally substituted by a C3-C6 carbocyclyl to provide a (carbocyclyl)-alkylene- of up to 9 total carbon atoms, or
R1 is —(C2-C6 alkylene)-X—R4, wherein X is an amide or carbamate functional group and R4 is C1-C6 alkyl,
with the proviso that the total number of carbon atoms in the (carbocyclyl)alkyl(ene) moieties of R1 is between 4 and 10 and R1 is not methyl, or
R1 is a first non-aromatic hydrophobic moiety; and
R2 is a second non-aromatic hydrophobic moiety,
wherein the first and second hydrophobic moieties provide the hydrophobic AF compound characterized by a clogP value of between about 4.4 to about 7.2,
or
wherein its drug linker moieties are represented by the structure(s) of:, or a salt thereof,
wherein HE is an optional Hydrolysis Enhancing Unit,
AO is absent or is a second subunit of A;
A′ is a second optional Stretcher Unit;
subscript a′ is 0 or 1, indicating the absence or presence of A′, respectively;
subscript x is 1 or 2;
Ra2 is hydrogen or —CH3 or —CH2CH3;
Ra3, at each instance, is independently hydrogen, —CH3 or —CH2CH3, or both Ra3 together with the nitrogen to which they are attached define an azetidinyl, pyrrolidinyl or piperidinyl heterocyclyl, in which a basic primary, secondary or tertiary amine so defined is optionally protonated as an acid addition salt form,
R34 is —CH3, —C(CH3)2, —CH2COOH, —CH2CH2COOH or —CH2CH2CH2CH2NH2; and
R35 is methyl, isopropyl, —CH2C(═O)NH2, —CH2COOH, —CH2CH2C(═O)NH2, —CH2CH2COOH, —CH2CH2CH2NHC(═NH)NH2, —CH2CH2CH2NH2, —CH2CH2CH2NH—C(═O)CH3, —CH2CH2CH2NH—C(═O)H, —CH2CH2CH2NHC(═NH)NH-2, —CH2CH2CH2CH2NH2—, —CH2CH2CH2CH2NH—C(═O)CH3, —CH2CH2CH2CH2NH—C(═O)H, —CH2CH2CH2NHC(═O)NH2, —CH2CH2CH2CH2NHC(═O)NH2 or —CH2CH2CH(OH)CH2NH2;
R2 is methyl; and
R1 is C1-C9 alkyl, optionally substituted by a C3-C6 carbocyclyl to provide a (carbocyclyl)-alkylene- of up to 9 total carbon atoms, or
R1 is —(C2-C6 alkylene)-X—R4, wherein X is an amide or carbamate functional group and R4 is C1-C6 alkyl,
with the proviso that the total number of carbon atoms in the (carbocyclyl)alkyl(ene) moieties of R1 is between 4 and 10 and R1 is not methyl, or
R1 is a first non-aromatic hydrophobic moiety; and
R2 is a second non-aromatic hydrophobic moiety,
wherein the first and second hydrophobic moieties provide the hydrophobic AF compound characterized by a clogP value of between about 4.4 to about 7.2.