A machine-assisted approach for the preparation of follow-on pharmaceutical compound libraries. Issue 2 (16th February 2018)

• Record Type: Journal Article
• Authors: Schotten, Christiane; Leist, Lisa G. T.; Semrau, A. Lisa; Browne, Duncan L.
• Is Part Of: Reaction chemistry & engineering. Volume 3:Issue 2(2018)
• Page Start: 210
• Page End: 215
• Publication Date: 2018-02-16
• Subjects: Reaction mechanisms (Chemistry) -- Periodicals; Chemical engineering -- Periodicals; Chemical engineering; Reaction mechanisms (Chemistry); Periodicals; 547.705
• DOI: 10.1039/c8re00010g
• Languages: English
• ISSNs: 2058-9883

Abstract

Abstract : Coupling of a continuous flow process to a robotic microwave device has led to a simple platform for the preparation of compound libraries, specifically the anti-migraine compound Zolmitriptan and several unknown analogues. 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.