Please use this identifier to cite or link to this item: doi:10.22028/D291-30944
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Title: Design and Synthesis of Bioisosteres of Acylhydrazones as Stable Inhibitors of the Aspartic Protease Endothiapepsin
Author(s): Jumde, Varsha R.
Mondal, Milon
Gierse, Robin M.
Unver, M. Yagiz
Magari, Francesca
van Lier, Roos C. W.
Heine, Andreas
Klebe, Gerhard
Hirsch, Anna
Language: English
Title: ChemMedChem : chemistry enabling drug discovery
Volume: 13
Issue: 21
Startpage: 2266
Endpage: 2270
Publisher/Platform: Wiley-VCH
Year of Publication: 2018
Publikation type: Journal Article
Abstract: Acylhydrazone-based dynamic combinatorial chemistry (DCC) is a powerful strategy for the rapid identification of novel hits. Even though acylhydrazones are important structural motifs in medicinal chemistry, their further progression in development may be hampered by major instability and potential toxicity under physiological conditions. It is therefore of paramount importance to identify stable replacements for acylhydrazone linkers. Herein, we present the first report on the design and synthesis of stable bioisosteres of acylhydrazone-based inhibitors of the aspartic protease endothiapepsin as a follow-up to a DCC study. The most successful bioisostere is equipotent, bears an amide linker, and we confirmed its binding mode by X-ray crystallography. Having some validated bioisosteres of acylhydrazones readily available might accelerate hit-to-lead optimization in future acylhydrazone-based DCC projects.
DOI of the first publication: 10.1002/cmdc.201800446
URL of the first publication:
Link to this record: hdl:20.500.11880/29154
ISSN: 1860-7187
Date of registration: 15-May-2020
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Pharmazie
Professorship: NT - Prof. Dr. Anna Hirsch
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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