Editorial [ Efficient Medicinal Chemistry (Guest Editor: Donald J. Kyle)]

Successful pharmaceutical companies are able to achieve a favorable financial balance between the upward pressure caused by increasing research costs and the downward pressure on the prices of commercial pharmaceuticals. These companies strive to conduct their research activities with an underlying strategic intent of constantly improving research efficiency as a main driver of attaining this critical balance. Lack of efficiency is likely to lead to a loss of competitive advantage, extended time to commercialization, and overall higher costs associated with the discovery and development of a new drug. Significant technological advances, capable of impacting research efficiency, have been made during the past decade, but accessing these technologies can require significant up-front and on-going financial, human resource, and infrastructure commitments. Achieving efficiency requires the careful and strategic implementation of these technologies, while appreciating that acquiring technologies alone will not guarantee success. The creative thinking that occurs in the laboratories of the medicinal chemists is at least of equal importance to the productivity-enhancing technologies that are also available in the laboratory. Consider the extreme example of knowing in advance exactly which molecule to synthesize to achieve the ideal balance of pharmacological potency, PKDM (pharmacokinetics and drug metabolism), safety, and bio-availability. This would mean that the medicinal chemist would need only to prepare a single molecule. If follows that this would require a single analytical profile and a single assay. The operational overhead associated with high-throughput synthesis, analysis, and screening would be unnecessary, and the highest research efficiency would be attained. Of course this is not possible because of the trial-anderror nature of the drug discovery process, but the concept is supportive of an argument that the goal of medicinal chemistry should be to synthesize as few molecules as possible in order to identify the highest quality, lowest risk, candidates for development. Working toward such a goal would represent movement toward a higher efficiency within discovery research. Chemistry as a discipline is somewhat unique in that the relevant scientific literature is vast, spanning over a century. In addition, chemistry is the one discipline within a multidisciplinary research team that becomes engaged at the earliest stages of the exploratory project and remains engaged throughout the commercial lifetime of the ultimate product. Access to prior, yet relevant, synthesis experience, simple yet effective data visualization, knowledge-based molecule design, and the ability to make reliable predictions of properties from chemical structure alone are all important ways of assisting a medicinal chemist in his movement toward more efficient experimentation. Although these types of tools are in their infancy it is clear that if they can be made into systems that the chemists will actually use and trust, then when combined with laboratory productivity-enhancing technologies there should be substantial and ongoing improvements in the efficiency of the research process. This special issue of CCHTS is dedicated to the presentation of various tools, systems, and processes that are aimed at assisting the medicinal chemist in the quest of working more efficiently, i.e. synthesizing as few compounds as possible to find the most "ideal" in a series.