Structure-Activity Results

In this Chapter we discuss the ways in which X-ray crystallographers have been able to study some stereochemical aspects of chemical and biochemical reactions in the solid state. Several types of experiments will be described. The first is the observation of reactions that occur within a crystal on exposure to radiation, and the second is the study of reactions that occur on the surfaces of crystals. The third involves the analyses of structures that can be considered representative of points on reaction pathways, and the fourth is the study of enzyme reactions from the point of view of substrate and inhibitor binding and deductions from site-directed mutagenesis studies. Finally the observation of a change in the diffraction pattern of a mixture as a chemical reaction occurs and the ways in which this effect can be monitored are described. 

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The validity of the Topliss scheme was tested by looking at structure-activity results for various drugs which had been reported in the literature. For example, the biological activity of nineteen substituted benzenesulfonamides (Fig. 9.19) have been reported. The second most active compound was the nitro-substituted analogue which would have been the fifth compound synthesized if the Topliss scheme had been followed. 

Ranitidine has fewer side-effects than cimetidine, lasts longer, and is ten times more active. Structure-activity results for ranitidine include the following ... 

A careful analysis of the structure-activity results in phenols containing another benzene nucleus linked directly or through a sulfide, sulfoxide or methylene... 

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