Searching for Drugs

In the earliest research with DET and the related dialkyltryptamines, the chemistry of metabolism was studied for any clues that could explain the activity of these materials. It must be remembered that this was in the heyday of the concept of psychotomimesis, the search for drugs that would imitate the psychotic state. What an appealing concept, that there might be a drug that could produce the syndrome of mental illness and thus be an accepted model for designing some treatment for it. There was a delicious search made at that time (the 1950 s) for names that could be given to these remarkable substances that would obscure any spiritual or positive aspects, so that one could present one s findings into the orthodox medical literature. 

How is the laboratory method called combinatorial chemistry similar to the search for drugs in nature ... 

Apart from interest in its synthesis and properties, some of the work on indolizines has been concerned with the search for drugs, for dyestuffs and for light-screening agents used in photographic emulsions. 

Fig. 14.4 Pharmacophore-based database searching for drug discovery. This example is based on a glucocorticoid receptor dataset (Morgan et al., 2002).

MY Galperin, EV Koonin. Searching for drug targets in microbial genomes. Curr Opin Biotechnol 10 571-578, 1999. 

It has been clear for several decades that an elevated concentration of plasma cholesterol attributable to increased concentrations of atherogenic lipoproteins (low-density lipoproteins [LDL] and remnant lipoproteins) is a major risk factor for the development of coronary heart disease (CHD) (Castelli et al., 1992 Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, 1993). The cholesterol biosynthetic pathway (Fig. 1) was a natural target in the search for drugs to reduce plasma cholesterol concentrations in the hope that these treatments would reduce the risk of CHD. However, early attempts to reduce cholesterol biosynthesis were disastrous. Tri-paranol, which inhibits the penultimate step in the pathway, was introduced into clinical use in the mid-1960s but was withdrawn from the... 

Fusetani N. Search for drug leads from Japanese marine invertebrates. J. Synth. Org. Chem. Jpn. 2004 62 1073-1079. 

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