Schotten, C;
Leist, LGT;
Semrau, AL;
Browne, DL;
(2018)
A machine-assisted approach for the preparation of follow-on pharmaceutical compound libraries.
Reaction Chemistry & Engineering
, 3
(2)
pp. 210-215.
10.1039/c8re00010g.
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Abstract
Follow-on drugs represent the majority of new drug introductions and show improved properties to the pioneer drug. In order to fast-follow, R&D needs to be able to quickly generate a library of analogues that can then be screened for desired properties. Here we have designed a hybrid machine-assisted approach which makes use of both multi-step continuous flow processing and robotic microwave reactors to generate a library of indoles over two technology steps (four reaction steps; diazotization, reduction, unmasking of the hydrazine and Fischer indole reaction). This ‘machine’ is then used to prepare a small library of hitherto unreported analogues of the 5-HT agonist Zolmitriptan in good yields, thus demonstrating that the integration and use of machines is a powerful tool to expedite drug discovery.
| Type: | Article |
|---|---|
| Title: | A machine-assisted approach for the preparation of follow-on pharmaceutical compound libraries |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1039/c8re00010g |
| Publisher version: | http://dx.doi.org/10.1039/c8re00010g |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | FISCHER INDOLE SYNTHESIS, OPTIMIZING REACTOR SYSTEMS, NITROSATED IN-SITU, ASCORBIC-ACID, CHEMICAL-SYNTHESIS, MASS-SPECTROMETRY, ORGANIC-SYNTHESIS, FLOW, OPTIMIZATION, ARYLATION |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharma and Bio Chemistry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10114373 |
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