Patent ID: 11944689
Assignee: SEAGEN INC.
Field: Pharmaceuticals (Chemistry)
Classification: CPC C  A | IPC A  C

Claim 15:
16. The Ligand Drug Conjugate compound of claim 15, wherein the auristatin that is released is an auristatin drug compound having the structure of:, or a pharmaceutically acceptable salt thereof or in a pharmaceutically acceptable salt form, wherein
the dagger indicates the site of covalent attachment of the nitrogen atom of the auristatin compound's secondary amine that provides a carbamate functional group, wherein —OC(═O)— of that functional group is Y′, on incorporation of the auristatin drug compound as -D into a Ligand Drug Conjugate compound in which subscript y is 2;
one of R10 and R11 is hydrogen and the other is C1-C8 alkyl,
R12 is hydrogen, C1-C8 alkyl, C3-C8 carbocyclyl, C6-C24 aryl, —X1—C6-C24 aryl, —X1—(C3-C8 carbocyclyl), C3-C8 heterocyclyl or —X1—(C3-C8 heterocyclyl);
R13 is hydrogen, C1-C8 alkyl, C3-C8 carbocyclyl, C6-C24 aryl, —X1—C6-C24 aryl, —X1—(C3-C8 carbocyclyl), C3-C8 heterocyclyl and —X1—(C3-C8 heterocyclyl);
R14 is hydrogen or methyl, or
R13 and R14 taken together with the carbon to which they are attached comprise a C3-C8 carbocyclo;
R15 is hydrogen or C1-C8 alkyl;
R16 is hydrogen, C1-C8 alkyl, C3-C8 carbocyclyl, C6-C24 aryl, —C6-C24—X1-aryl, —X1—(C3-C8 carbocyclyl), C3-C8 heterocyclyl and —X1—(C3-C8 heterocyclyl);
R17 independently are hydrogen, —OH, C1-C8 alkyl, C3-C8 carbocyclyl and O—(C1-C8 alkyl);
R18 is hydrogen or optionally substituted C1-C8 alkyl;
R19 is —C(R19A)2—C(R19A)2—C6-C24 aryl, —C(R19A)2—C(R19A)2—(C3-C8 heterocyclyl) or —C(R19A)2—C(R19A)2—(C3-C8 carbocyclyl), wherein C6-C24 aryl and C3-C8 heterocyclyl are optionally substituted;
R19A independently are hydrogen, optionally substituted C1-C8 alkyl, —OH or optionally substituted —O—C1-C8 alkyl;
R20 is hydrogen or C1-C20 alkyl, C6-C24 aryl or C3-C8 heterocyclyl, optionally substituted, or —(R47O)m—R48, or —(R47O)m, —CH(R49)2;
R21 is C1-C8 alkylene-(C6-C24 aryl) or —C1-C8 alkylene-(C5-C24 heteroaryl), optionally substituted, or C1-C8 hydroxylalkyl, or optionally substituted C3-C8 heterocyclyl;
Z is O, S, NH, or NR46;
R46 is optionally substituted C1-C8 alkyl;
subscript m is an integer ranging from 1-1000;
R47 is C2-C8 alkyl;
R48 is hydrogen or C1-C8 alkyl;
R49 independently are —COOH, —(CH2)n—N(R50)2, —(CH2)n—SO3H, or —(CH2)n—SO3—C1-C8 alkyl;
R50 independently are C1-C8 alkyl, or —(CH2)n—COOH;
subscript n is an integer ranging from 0 to 6; and
X1 is C1-C10 alkylene, or wherein the released auristatin drug compound incorporated into —D with covalent attachment through a carbamate functional group is monomethylauristatin E (MMAE) or monomethylauristatin F (MMAF).