Discovery research medicinal chemists

Chemists participating in a narrowly defined, initial development campaign engage in teamwork more than their colleagues in medicinal chemistry. As a result of this and other factors, individual contributions can be more difficult to quantify than in discovery research. Process chemists are partly judged by how completely and promptly they carry out assigned tasks that represent important elements of the whole effort. 

Molecular structure and properties are key concepts in drug design, but they may not mean the same to all medicinal chemists, not to mention other researchers involved in drug discovery and development such as biochemists, pharmacologists and toxicologists (see Chapter 2). It is therefore the merit of this book to offer a rationalization of these concepts with a view to advocating their value and clarifying their use. 

In silico ADME profiling of compound libraries in early discovery has become a valuable addition to the research toolbox of computational and medicinal chemists. A computational alert was developed by Lipinski based on the physico-chemical... 

There is a considerable interest in computational models to predict the safety of NCEs in the drug discovery and development phases. Insight into the safety pharmacological potential of a scaffold or series of structures early in the drug discovery process could help the medicinal chemists to prioritize particular scaffolds or hits or alternatively can contribute halting the discovery process for a given research project. The main safety... 

Although numerous structural types have been synthesized to date, we expect research to continue in this area. Several companies, not mentioned here, have ongoing Class III discovery programmes. As medicinal chemists begin to take advantage of information from new pharmacological studies and clinical experience, we expect to see agents with increased selectivity (for example, normal vs. ischaemic tissue), improved efficacy and improved safety. 

This research has progressed only because the science was willing to allow Nature s biomolecules to intervene earlier than is usual for medicinal chemistry protocols. The role of biomolecules has been elevated from spectator to key player, to guide and instruct the synthesis of potent inhibitor molecules, while the medicinal chemist acts to facilitate this process. The in situ selection and assembly of fragments could in principle be screened by an activity assay or by any number of analytical techniques for drug discovery, however, it is a... 

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