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Asymmetric Synthesis and Biological Evaluation of Glycosidic Prodrugs for a Selective Cancer Therapy

✍ Scribed by Lutz F. Tietze; J. Marian von Hof; Birgit Krewer; Michael Müller; Felix Major; Heiko J. Schuster; Ingrid Schuberth; Frauke Alves

Publisher
John Wiley and Sons
Year
2008
Tongue
English
Weight
390 KB
Volume
3
Category
Article
ISSN
1860-7179

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✦ Synopsis

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 (−)‐(1__S__)‐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 (−)‐(1__S__)‐19 was performed by arylation of the enantiomerically pure epoxide (+)‐(S)‐29 (≥98 %ee).

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✍ Lutz F. Tietze; Tobias Herzig; Tim Feuerstein; Ingrid Schuberth 📂 Article 📅 2002 🏛 John Wiley and Sons 🌐 English ⚖ 226 KB 👁 2 views

This paper describes novel seco-analogues 25-27 of the cytotoxic antibiotic CC-1065 (1) and their prodrugs 5, 6a, and 6b, for antibody-directed enzyme prodrug therapy (ADEPT). The partially hydrogenated seco-CCI-analogue 7 and the corresponding methyl-CCI analogues 8a and 8b were synthesized by alky