The future of medicinal chemistry as both a pure and an applied science has been considered relative to trends that are already having a significant impact upon drug discovery and development. After quickly reviewing how medicinal chemistry has been practiced to date, topics considered into the future include: pursuing therapeutic efficacy, addressing 3D structure within database settings, assuring absorption, directing distribution, controlling metabolism, optimizing elimination, and avoiding toxicity. It is suggested that as the exploration of these topics proceeds into the new millennium by deploying combinatorial chemistry coupled to high-throughput screening, medicinal chemistry will play a key role as a central interpreter of the underlying structureactivity relationships such that the overall process of drug discovery and development will be knowledge-generating. As fundamental knowledge accumulates across all of these areas, virtual approaches will eventually become firmly anchored to experimental and theoretical databases having validated clinical predictability. The potential impact of some of the recent trends in process chemistry, and in analytical chemistry using X-ray diffraction as an exemplary method, are additionally highlighted before reiterating the article's major points in a summary section. From this purview, the summary also considers the education of future medicinal chemists, notes potential issues related to the future of pharmaceutical-related intellectual property, and concludes by alluding to a brewing paradox between enhanced knowledge and enhanced molecular diversity relative to the future discovery of new drugs.
The benefits of utilizing marketed drugs as starting points to discover new therapeutic agents have been well documented within the IUPAC series of books that bear the title Analogue-based Drug Discovery (ABDD). Not as clearly demonstrated, however, is that ABDD also contributes to the elaboration of new basic principles and alternative drug design strategies that are useful to the field of medicinal chemistry in general. After reviewing the ABDD programs that have evolved around the area of microtubule-stabilizing chemo-therapeutic agents, the present article delineates the associated research activities that additionally contributed to general strategies that can be useful for prodrug design, identifying pharmacophores, circumventing multidrug resistance (MDR), and achieving targeted drug distribution.
The evolution that has taken place in medicinal chemistry practice as a result of
major advances in genomics and molecular biology arising from the Human Genome
Project has carried with it an extensive additional working vocabulary that has
become both integrated and essential terminology for the medicinal chemist. Some
of this augmented terminology has been adopted from the many related and
interlocked scientific disciplines with which the modern medicinal chemist must
be conversant, but many other terms have been introduced to define new concepts
and ideas as they have arisen. In this supplementary Glossary, we have attempted
to collate and define many of the additional terms that are now considered to be
essential components of the medicinal chemist’s expanded repertoire.