Svetlana O Doronina,Toni Beth Kline,Scott Jeffrey,Peter D Senter,Damon Meyer
申请号：
US14502210
公开号：
US09522194B2
申请日:
2014.09.30
申请国别(地区):
US
年份:
2016
代理人:
摘要：
Auristatin peptide analogs of MeVal-Val-Dil-Dap-Phe (MMAF) having a carboxylic acid equivalent at the C-terminal phenylalanine were prepared and attached to ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand-drug conjugates were active in vitro and in vivo in inhibiting cell proliferation and are represented by the general structure ofLv-[(LU)0-1-(D)1-4]p wherein L- is Ligand unit； LU is a Linker unit (LU)； v is 1； p is an number ranging from about 1 to about 20； and D is a drug moiety having the formula:wherein the moiety —N(R9)Z1 is a phenylalanine bioisostere, wherein Z1 is —CH(R10)Z2 so that the phenylalanine bioisostere has the structure of Formula A:and wherein the substituents R2-R10, X1 and Z2 are as defined.
