The Dominant Parameter is Structural

Analogues Produced by Isosteric Variations 1.1.3.1 The Dominant Parameter is Structural 

Structural factors are important when the portion of the molecule involved in the isosteric change serves to maintain other functions in a particular geometry. That is the case for tricyclic psychotropic dmgs (Fig. 1.5). 

For the two antidepressants (imipramine and maprotiline), the bioisosterism is geometrical insofar that the dihedral angle a formed by the two benzo rings is comparable a = 65° for the dibenzazepine and a = 55° for the dibenzocyclohepta-diene [12]. This angle is only 25° for the neuroleptic phenothiazines and for the thioxanthenes. In these examples, the part of the molecule modified by isosterism is not involved in the interaction with the receptor. It serves only to position correctly the other elements of the molecule. 

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