Designing Multi-Target Drugs
Chapter 18: Discovery of Multi-Target Agents for Neurological Diseases via Ligand Design
Published:28 Mar 2012
Special Collection: 2012 ebook collection , 2011-2015 industrial and pharmaceutical chemistry subject collectionSeries: Drug Discovery
M. L. Bolognesi, C. Melchiorre, C. J. Van der Schyf, and M. Youdim, in Designing Multi-Target Drugs, ed. J. R. Morphy and C. J. Harris, The Royal Society of Chemistry, 2012, ch. 18, pp. 290-315.
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The incidence of neurological disorders in the developed world is rising in concert with an increase in human life expectancy, due in large part to better nutrition and health care. Even as drug discovery efforts are refocused on these disorders, there has been a dearth in the introduction of new disease-modifying therapies to prevent or delay their onset, or reverse their progression. Mounting evidence points to complex and heterogeneous etiopathologies that underlie these diseases. Therefore, it is unlikely that disorders in this class will be mitigated by any single drug that acts exclusively on a single pathway or target. The rational design of novel drug entities with the ability to simultaneously address multiple drug targets of a complex pathophysiology has recently emerged as a new paradigm in drug discovery. Similarly to the concept of multi-target agents within the psychopharmacology field, ligand design has gained an increasing prominence within the medicinal chemistry community. In this chapter we discuss several examples of select chemical scaffolds (polyamines, alkylxanthines, and propargyl carbamates) wherein these concepts were applied to develop novel drug candidates for Alzheimer's disease and Parkinson's disease.