The medicinal chemist plays the most important role in drug design, discovery and development. The primary goal is to discover leads and optimize them to develop clinically useful drug candidates. This process requires the medicinal chemist to deal with large sets of data containing chemical descriptors, pharmacological data, pharmacokinetics parameters, and in silico predictions. The modern medicinal chemist has a large number of tools and technologies to aid him in creating strategies and supporting decision-making. Alongside with these tools, human cognition, experience and creativity are fundamental to drug research and are important for the chemical intuition of medicinal chemists. Therefore, fine-tuning of data processing and in-house experience are essential to reach clinical trials. In this article, we will provide an expert opinion on how chemical intuition contributes to the discovery of drugs, discuss where it is involved in the modern drug discovery process, and demonstrate how multidisciplinary teams can create the optimal environment for drug design, discovery, and development.

The recent disclosure of type I 1/2 inhibitors for p38α MAPK demonstrated how the stabilization of the R-spine can be used as a strategy to greatly increase the target residence time (TRT) of inhibitors. Herein, for the first time, we describe N-acylhydrazone and selenophene residues as spine motifs, yielding metabolically stable inhibitors with high potency on enzymatic, NanoBRET, and whole blood assays, improved metabolic stability, and prolonged TRT.

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Phosphorus oxychloride (POCl 3 ) is a colorless liquid, with a molar mass of 153.33 g/mol and 1.645 g/mL in density. Its handling and disposal must be done carefully because it reacts violently with water forming phosphoric acid and hydrochloric acid. This reagent is extremely versatile and it is used from the production of flame-retardants to intermediates to drugs. The present article describes many techniques for the production of POCl 3, from its halides derivatives (PX 3 ), phosphorous oxides or even by residual recovery.