A high-throughput synthesis of 1,2,4-oxadiazole and 1,2,4-triazole libraries in a continuous flow reactor

Abstract

We report herein a high-throughput methodology for the synthesis of 1,2,4-oxadiazole and 1,2,4-triazole small-molecule libraries using an integrated synthesis and purification platform.

In vitro anti-TB properties, in silico target validation, molecular docking and dynamics studies of substituted 1,2,4-oxadiazole analogues against Mycobacterium tuberculosis

“…However, 1,2,4-oxadiazole have also impacted the medicinal chemistry research after the launch of first-in-class marketed drug, oxolamine as a cough suppressant, and the subsequent discovery of commercial products like prenoxdiazine, fasiplon, pleconaril, proxazole, atalureri and butalamine 29–31 . These clinical success in parallel gave an impetus to the synthetic chemists to design innovative strategies for the economic, ecofriendly and rapid synthesis of 1,2,4-oxadiazole chemical libraries to accelerate the drug discovery process 32 , 33 . In the past 40 years, 1,2,4-oxadiazole scaffold has been extensively investigated for diverse biological activities 34 including anti-inflammatory 35 , 36 , analgesic 37 , anaesthetic 38 , anthelmintic 39 , antiallergic 40 , anti-Alzheimer 41 , antibacterial 42 , 43 , anticancer 44–46 , anticonvulsant 47 , 48 , antidepressant 49 , antifungal 50 , anti-HIV 51 , antiparasitic 52 , antiplatelet and antithrombotic 53 , anti-tubercular 54 , antitussive 55 , antiviral 56 , 57 , insecticidal 58 , monoamine oxidase inhibition 59 , muscarinic receptor agonists 60 , selective G-protein bile acid receptor 1 (GPBAR1) agonists 61 and selective H 3 receptor antagonists 62 activities.…”

Understanding flow chemistry for the production of active pharmaceutical ingredients

“…Specifically, a conjure flow reactor was used as a library synthesis platform and the system relied on segmented flow. This synthesis with integrated flow technology, popularly known as SWIFT, provided a high efficiency in the synthesis and purification of six compounds per hour ( Bogdan and Wang, 2015 ).…”

The Medicinal Chemistry in the Era of Machines and Automation: Recent Advances in Continuous Flow Technology

“…In the past few years, a number of examples have been reported showing the profitable use of automated flow synthesis of compound collections readily available for biological testing. − Among these, it is worth mentioning the system realized by Djuric and co-workers at AbbVie in 2011 is probably one of the first fully integrated systems for the generation of diverse classes of compounds under automated flow modality (Figure ). The system, namely SWIFT (Synthesis With Integrated Flow Technology), was based on an Accendo Conjure flow reactor integrated with autosampler and preparative HPLC/MS device (Figure ) to conduct different chemical transformations, including amide bond and urea formation, reductive amination reactions, Huisgen cycloaddition for triazole synthesis, nucleophilic displacement, and sulfonylation reactions and to obtain highly pure products.…”