Convergent pharmacophores

Figure 1.13 A suggestive structural correspondence between the ACE inhibitor Quinalapril (left) and bradykinin was used to design novel B2 receptor antagonists, one of them shown on the right [63], For details of this convergent pharmacophore strategy, see the text.

These few examples were chosen to illustrate different elements of convergence that can be exploited to utilize suggestive pharmacophore relations for cross-fertilizing medicinal chemistry projects on targets in the same or different protein families. However, the applied pharmacophoric relations did not reveal generic... 

In summary, each parent in this method represents a QSAR equation with randomly chosen variables, and the purpose of the calculation is to evolve from the initial population of the QSAR equations to the population with the highest average value of the fitness function. In the course of the GA-PLS process, the initial number of members of the population (100) is maintained while the average value of the fitness function for the whole population converges to a high number. The best model is characterized by the highest value of the fitness function as well as by specific descriptor selection (descriptor pharmacophore) that affords such a model. 

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