Novel, selective indole-based ECE inhibitors: lead optimization via solid-phase and classical synthesis.

Michael Brands; Jens-Kerim Ergüden; Kentaro Hashimoto; Dirk Heimbach; Christian Schröder; Stephan Siegel; Johannes-Peter Stasch; Stefan Weigand

doi:10.1016/j.bmcl.2005.06.085

PubMed · 16085415

Novel, selective indole-based ECE inhibitors: lead optimization via solid-phase and classical synthesis.

Michael Brands·Jens-Kerim Ergüden·Kentaro Hashimoto·Dirk Heimbach·Christian Schröder·Stephan Siegel·Johannes-Peter Stasch·Stefan Weigand

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Abstract

A novel class of indole-based endothelin-converting enzyme (ECE) inhibitors was identified by high throughput screening. We report systematic optimization of this compound class by means of classical and solid-phase chemistry. Optimized compounds with a bisarylamide side chain at the 2-position of the indole skeleton exhibit low-nanomolar activity on ECE.

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Aspartic Acid Endopeptidases Combinatorial Chemistry Techniques Drug Evaluation, Preclinical Endothelin-Converting Enzymes Enzyme Inhibitors Humans Indoles Inhibitory Concentration 50 Metalloendopeptidases Structure-Activity Relationship Journal Article

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Michael Brands, Jens-Kerim Ergüden, Kentaro Hashimoto, Dirk Heimbach, Christian Schröder, Stephan Siegel, Johannes-Peter Stasch, Stefan Weigand. 2005-10-01. Novel, selective indole-based ECE inhibitors: lead optimization via solid-phase and classical synthesis.. https://doi.org/10.1016/j.bmcl.2005.06.085

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