Abstract:
:A severe limitation in cancer therapy is the often insufficient differentiation between malign and benign tissue using known chemotherapeutics. One approach to decrease side effects is antibody-directed enzyme prodrug therapy (ADEPT). We have developed new glycosidic prodrugs such as (-)-(1S)-26 b based on the antibiotic (+)-duocarmycin SA ((+)-1) with a QIC(50) value of 3500 (QIC(50)=IC(50) of prodrug/IC(50) of prodrug+enzyme) and an IC(50) value for the corresponding drug (prodrug+enzyme) of 16 pM. The asymmetric synthesis of the precursor (-)-(1S)-19 was performed by arylation of the enantiomerically pure epoxide (+)-(S)-29 (> or = 98 % ee).
journal_name
ChemMedChemjournal_title
ChemMedChemauthors
Tietze LF,von Hof JM,Krewer B,Müller M,Major F,Schuster HJ,Schuberth I,Alves Fdoi
10.1002/cmdc.200800250subject
Has Abstractpub_date
2008-12-01 00:00:00pages
1946-55issue
12eissn
1860-7179issn
1860-7187journal_volume
3pub_type
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