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Streamlined approach to high‐quality purification and identification of compound series using high‐resolution MS and NMR
Author(s) -
Mühlebach Anneke,
Adam Joachim,
Schön Uwe
Publication year - 2011
Publication title -
journal of separation science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.72
H-Index - 102
eISSN - 1615-9314
pISSN - 1615-9306
DOI - 10.1002/jssc.201100382
Subject(s) - drug discovery , throughput , computer science , process (computing) , lead (geology) , quality (philosophy) , high resolution , biochemical engineering , combinatorial chemistry , resolution (logic) , chemistry , process engineering , engineering , artificial intelligence , operating system , telecommunications , biochemistry , philosophy , remote sensing , epistemology , geomorphology , wireless , geology
Automated medicinal chemistry (parallel chemistry) has become an integral part of the drug‐discovery process in almost every large pharmaceutical company. Parallel array synthesis of individual organic compounds has been used extensively to generate diverse structural libraries to support different phases of the drug‐discovery process, such as hit‐to‐lead, lead finding, or lead optimization. In order to guarantee effective project support, efficiency in the production of compound libraries has been maximized. As a consequence, also throughput in chromatographic purification and analysis has been adapted. As a recent trend, more laboratories are preparing smaller, yet more focused libraries with even increasing demands towards quality, i.e. optimal purity and unambiguous confirmation of identity. This paper presents an automated approach how to combine effective purification and structural conformation of a lead optimization library created by microwave‐assisted organic synthesis. The results of complementary analytical techniques such as UHPLC‐HRMS and NMR are not only regarded but even merged for fast and easy decision making, providing optimal quality of compound stock. In comparison with the previous procedures, throughput times are at least four times faster, while compound consumption could be decreased more than threefold.