SLOW-RELEASE CONJUGATES OF SN-38

摘要

Conjugates of SN-38 that provide optimal drug release rates and minimize the formation of the corresponding glucuronate are described. The conjugates release SN-38 from a polyethylene glycol through a β-elimination mechanism.

主权项

1. A conjugate of formula (I) wherein PEG is linear or branched and, when q is 2-8, multi-armed, polyethylene glycol; X is O, NH, (CH2)m, OC(═O)(CH2)m, or NHC(═O)(CH2)m wherein m=1-6; L is (CH2)r or (CH2CH2O)p(CH2)r, wherein r=1-10 and p=1-10; R1 is CN or SO2NR22, wherein each R2 is independently alkyl, aryl, heteroaryl, alkylalkenyl, alkylaryl, or alkylheteroaryl, each optionally substituted, or two R2 taken together can form a ring; Y is COR3 or SO2R3, wherein R3═OH, alkoxy, or NR42, wherein each R4 is independently alkyl, substituted alkyl, or two R4 taken together can form a ring; and q is 1-8.