SAR of the 5-hydroxytryptamine Receptor Antagonists

The 5-hydroxytryptamine 5-HT3 receptor antagonists are currently used in the treatment of chemotherapy and radiotherapy induced emesis. The compounds are based on the parent structure shown in Fig. 9.10, the aromatic systems include mono- and bicyclic rings, with and without heteroatoms, and with various substitution patterns. This range of structural variation makes it difficult to analyze SAR of these compounds. 

Since SVM has been applied to drug design [16], and the prediction of beta-turns and alpha-turn types of proteins [17] was also rather successful. SVM has been used to the SAR study of 5-HT3 antagonists 

The calculated molecular descriptors along with observed activity data of 26 5HT3 antagonists are presented in Table 9.5 [93]. The classification of compounds (shown in Table 9.5, l=inactive 2=active) are based on their quantitative (ED50) data of activities. 

The molecular descriptors used are as follows CMR (Calculated molar refractivity), pZ (Z component of the dipole moment), HOMO (Energy of the highest occupied molecular orbital), FZ (9), FY (6) and FY (11) (Z and Y are the components of the electric field at specified grid points), VDWE (4) (The van der Waal s energy of the interaction of a carbon atom at a specified grid point), ALP (3) (The self atom polarizability of the specified atom). 

Based on the above-mentioned results, the criterion for samples with high activity can be expressed as follows  

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