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Auriestatin drug linker conjugates
专利权人:
INC.;SEATTLE GENETICS
发明人:
SENTER, PETER,DORONINA, SVETLANA,BOVEE, TIMOTHY
申请号:
ES09721267
公开号:
ES2523033T3
申请日:
2009.03.18
申请国别(地区):
ES
年份:
2014
代理人:
摘要:
A compound having the formula: ** Formula ** L- (LU-D) p or a pharmaceutically acceptable salt or solvate thereof; wherein L is the ligand unit, LU is a linker unit and D is a drug unit, L is a peptide, polypeptide or protein that specifically binds to a population of target cells; LU has the formula -Aa-Ww-, Ww is a sequence of w selected independently of dirradical amino acids, in which the W proximal to the drug unit (W1) is a natural amino acid that is not an amino acid D, and is linked by means of a peptide bond to the drug unit, and in which each remaining W unit is independently selected from the group consisting of glycine and the isomers D of alanine, arginine, aspartic acid, asparagine, histidine, glutamine acid, glutamine, phenylalanine , lysine, leucine, serine, tyrosine, threonine, isoleucine, tryptophan and valine, with the proviso that W1 cannot form a secondary amide with the amino acid of the C-terminus of D and that the peptide bond can be cleaved by an intracellular protease, w it is an integer between 2 and 12, A is a spreading unit, it is already 1 or 2; p is an integer from 1 to 20; and D has the formula: ** Formula ** in which the wavy line indicates the peptide bond with LU; R1 and R225 are independently selected from the group consisting of -H and C1-C8 alkyl, with the proviso that both R1 and R2 are not -H; R3 is selected from the group consisting of -H, -C1-C8 alkyl, C3-C8 carbocycle, -aryl, -C1-C8 alkyl aryl, -X1- (C3-C8 carbocycle), -C3-C8 heterocycle and -X1- (C3-C8 heterocycle); R4 is selected from the group consisting of -H, -C1-C8 alkyl, -C3-C8 carbocycle, -aryl, -X1-aryl, -C1-C8 alkyl- (C3-C8 carbocycle), -C3-C8 heterocycle and -X1 - (C3-C8 heterocycle); R5 is selected from the group consisting of -H and methyl; or R4 and R5 together form a carbocyclic ring and have the formula - (CRaRb) n- in which Ra and Rb are independently selected from the group consisting of -H and -C1-C8 alkyl and n is selected from the group consisting of 2,
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