Doronina, Svetlana O.,Senter, Peter D.,Toki, Brian E.,Ebens, Allen J.,Kline, Toni Beth,Polakis, Paul,Sliwkowski, Mark X.,Spencer, Susan D.
申请号：
ES12157788
公开号：
ES2557389T3
申请日:
2004.11.05
申请国别(地区):
ES
年份:
2016
代理人:
摘要：
A conjugate having the formula : ** ** Formula or a pharmaceutically acceptable salt or solvate thereof wherein: Ab is an antibody, A is a frame unit, a is 0 or 1, each W is independently Amino Acid unit, w is an integer ranging from 0 to 12, Y is a spacer unit, and is 0, 1 or 2, p ranges from 1 to 20, and DF is a drug unit having the formula: ** ** formula wherein independently of each location: R2 is selected from H and C1-C8 alkyl R3 is selected from H, C1-C8 alkyl, C3-C8 carbocycle, aryl, alkaryl C1-C8, C1-C8 alkyl- (C3- C8 carbocycle), C3-C8 heterocycle and C1-C8 alkyl- (C3 heterocycle C8) R4 is selected from H, C1-C8 alkyl, C3-C8 carbocycle, aryl, alkaryl C1-C8, C1-C8 alkyl- (C3- C8 carbocycle), C3-C8 heterocycle and C1-C8 alkyl- (C3 heterocycle C8) R5 is selected from H and methyl or: R4 and R5 together form a carbocyclic ring and have the formula - (CRaRb) n- wherein Ra and Rb are independently selected from H, C1-C8 alkyl and C3-C8 carbocycle and n is selected from 2, 3, 4, 5 and 6 R6 is selected from H and C1-C8 alkyl R7 is selected from H, C1-C8 alkyl, C3-C8 carbocycle, aryl, alkaryl C1-C8, C1-C8 alkyl- (C3- C8 carbocycle), C3-C8 heterocycle and C1-C8 alkyl- (C3 heterocycle C8) each R8 is independently selected from H, OH, C1-C8 alkyl, C3-C8 carbocycle and O- (C1-C8) R9 is selected from H and C1-C8 alkyl R10 is selected from aryl and C3-C8 heterocycle Z is O, S, NH or NR12, wherein R12 is C1-C8 alkyl R11 is selected from H, C1-C20 alkyl - (R13O) m-R14 and - (R13O) m-CH (R15) 2 m is an integer ranging from 1 to 1000 R13 is C2-C8 alkyl R14 is H or C1-C8 alkyl each occurrence of R15 is independently H, COOH, - (CH2) nN (R16) 2, - (CH2) n-SO3H, or - (CH2) n-SO3-C1-C8 each occurrence of R16 is independently H, C1-C8 alkyl or - (CH2) n-COOH n is an integer ranging from 0 to 6.Un conjugado que tiene la Fórmula la:**Fórmula** o una sal o un solvato farmacéuticamente aceptables del mismo en el que: Ab es un anticuerpo, A es una unidad Bastidor, a es 0 o 1, cada W
