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Design and Synthesis of New Pyrazole‐Based Heterotricycles and their Derivatization by Automated Library Synthesis
Author(s) -
Fricero Prisca,
Bialy Laurent,
Czechtizky Werngard,
Méndez María,
Harrity Joseph P. A.
Publication year - 2020
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202000187
Subject(s) - adme , derivatization , drug discovery , pyrazole , workflow , combinatorial chemistry , chemistry , computer science , organic chemistry , mass spectrometry , database , biochemistry , chromatography , in vitro
Small‐molecule heterocycles bearing orthogonal functionality have the potential to deliver diverse structural motifs that aid the drug‐discovery effort. This work highlights how a readily assembled N ‐hydroxyethyl pyrazole trifluoroborate offers rapid access to architecturally distinct 5‐6‐6‐ and 5‐7‐6‐fused tricyclic compounds. This chemistry is not only amenable to single compound synthesis, but also to high‐throughput experimentation. It gives easy access to diverse compound arrays with various physicochemical and ADME profiles by fully automated library synthesis. The combination of the high‐throughput experimentation with rapid testing of the compounds in an integrated physicochemical and ADME profiling workflow allows accelerated design of novel lead compounds in drug‐discovery projects.