Issue: Vol. 42

The impact of flow chemistry in the drug discovery process

Early drug discovery programmes have undergone continuous improvements over the past two decades. The industry has seen a dramatic shift towards the acceptance and implementation of continuous flow techniques, as researchers seek to implement new enabling technologies to reduce the time and cost of bringing novel drugs to market. Flow chemistry has made an impact in most areas of drug discovery, enabling access to new chemistries that are not possible with traditional batch methods, improving reaction efficiencies, saving resources, and enhancing process safety. This article looks at how the development of automated techniques – combined with integrated synthesis, purification and analysis – has greatly increased the speed with which novel compounds can be delivered to rapidly progress early stages of drug discovery.

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Organometallics in Flow: Scalable synthesis of Mg- and Zn-organometallics

The benefits of using flow chemistry for fast, very exothermic, and dangerous processes has been widely acknowledged and demonstrated within the last few decades. Discussed in this article are the particular advantages that can be gained when using continuous processing for the formation and consumption of magnesium and zinc organometallic intermediates especially considering significant process improvements in terms of safety, scalability, selectivity, and sustainability. Appropriate technology applicable to the process, its scalability, and its application for a particular magnesium- and zinc-based reagent emphasizes that continuous processing can be used for either metal interchangeably depending on reagent processing needs.

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Nice drug if you can get it. Can’t get it if you try?* On the current scarcity of semaglutide (et alia).

The demand for incretin-based peptide drug substances such as semaglutide and tirzepatide to treat obesity has led to shortages of these drugs for diabetics and to plans for manufacturing these and other incretin peptides on an unprecedented scale in the future. Where solid phase synthesis (SPPS) is the chosen method of manufacture, the scale of these processes could possibly exhaust current SPPS reactor capacity. This article addresses the supply chain shortages of incretin-based drugs, the manufacturing process bottlenecks, drug costs, as well as the environmental burden, and suggests some solutions. It aims to create a discussion.

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High Potency Molecules: The Importance of Excellent Chemistry in their Successful Delivery

The high potency drug market is an exciting place and is likely only going to evolve. In this article, Rob Crook and Jean-Baptiste Vendeville discuss the current considerations needed when developing a synthesis for a HPAPI, as well as the challenges faced by these complex molecules, in particular ADCs. They will first highlight the development and growth of the market before a short review of the innovations being undertaken that can lead to lower costs and more efficient use of time and resources. Overall, they discuss how the requirement for excellent chemistry and innovation, along with exceptional route design, will be critical to the successful development of high potency molecules to secure their future potential as treatments.

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