Antihistamines isosteric substitution

Similar types of isosteric substitution can be seen in the evolution of antihistamines with the addition of ting to chain transformations and ring formation. The conversion... 

The isosteric relationship of benzene and thiophene has often led medicinal chemists to substitute the sulfur containing heterocycle for benzene drugs in biologically active molecules. That this relationship has some foundation in fact is attested by the observation that the resulting analogs often possess full biologic activity. Alkylation of the diamine, 71 (obtained from aniline and the chloroethylamine), with 2-chloromethylthiophene affords the antihistamine methaphenylene (72) The correspond-... 

For enhanced effectiveness is antihistaminics it is essential that one of the aromatie moieties is a-pyridyl while the second substituent on the N atom eould be either a benzyl funetion of a substituted benzyl group or one of the isosteres of the benzyl moiety, e.g., thenyidiamine, pyrilamine, ete. 

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