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Seamless Integration of Dose‐Response Screening and Flow Chemistry: Efficient Generation of Structure–Activity Relationship Data of β‐Secretase (BACE1) Inhibitors
Author(s) -
Werner Michael,
Kuratli Christoph,
Martin Rainer E.,
Hochstrasser Remo,
Wechsler David,
Enderle Thilo,
Alanine Alexander I.,
Vogel Horst
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201309301
Subject(s) - drug discovery , automation , work flow , computer science , process (computing) , computational biology , chemistry , combinatorial chemistry , third generation , productivity , biochemical engineering , nanotechnology , engineering , biochemistry , biology , materials science , manufacturing engineering , mechanical engineering , operating system , telecommunications , macroeconomics , economics
Drug discovery is a multifaceted endeavor encompassing as its core element the generation of structure‐activity relationship (SAR) data by repeated chemical synthesis and biological testing of tailored molecules. Herein, we report on the development of a flow‐based biochemical assay and its seamless integration into a fully automated system comprising flow chemical synthesis, purification and in‐line quantification of compound concentration. This novel synthesis‐screening platform enables to obtain SAR data on b‐secretase (BACE1) inhibitors at an unprecedented cycle time of only 1 h instead of several days. Full integration and automation of industrial processes have always led to productivity gains and cost reductions, and this work demonstrates how applying these concepts to SAR generation may lead to a more efficient drug discovery process.