Prodrugs and drug-macromolecule conjugates that have controlled drug release rates

摘要

A compound of the formula ** Formula ** where Z is the residue of a macromolecule; L 'is the residue of a link; D is the residue of a drug; X is O or S; A is alkenylene (C2), aryl or is absent; each R1 and R2 is independently H; CH; NO2; optionally substituted aryl; optionally substituted heteroaryl; optionally substituted alkenyl; optionally substituted alkynyl; or each R1 and R2 is independently COR3 or SOR3 or SO2R3 where R3 is H or optionally substituted alkyl; optionally substituted aryl; optionally substituted heteroaryl; optionally substituted alkenyl; optionally substituted alkynyl; or OR or NR2 where each R is independently H or optionally substituted alkyl; or each R1 and R2 is independently SR4 where R4 is optionally substituted alkyl; optionally substituted aryl; optionally substituted heteroaryl; optionally substituted alkenyl; or optionally substituted alkynyl; where optional substituents are selected from the group consisting of electron donor groups such as C1-C4 alkyl; C1-C4 alkoxy; C1-C4 alkylthio; Not me; alkylamino; and dialkylamino; and groups 30 electron attractors such as halogen; difluoromethyl; trifluoromethyl, nitro; cyano; C (O) R, where R is H, C1-C4 alkyl, C1-C4 alkoxy or amino; and SOR and SO2R, where R is C1-C4 alkyl, aryl, or heteroaryl, where these various optional substituents may be linked to aryl or heteroaryl rings, which several substituents may be the same or different; where R1 and R2 may be joined to form a 3-8 member ring; and where R1 and R2 cannot be H; where R5 is H or (C1-6) alkyl.