Publication Details (including relevant citation information): Lipinski, C. A., Journal of medicinal chemistry, 1983, 26 (1), pp 1-6
Abstract: A process of bioisosteric drug design is described whereby, in a manner analogous to synthesis, key portions of an effector molecule are successively replaced by pharmacophores or bioisosteres. This process, when applied to histamine, leads to the competitive histamine H2-receptor antagonist prototype 3-amino-5-(2-amino-4-pyridyl)-1,2,4-triazole (7). The biaryl nature of 7 fixes internitrogen distances, and comparison of these with histamine suggests that 7 shares structural features more in common with histamine trans rather than histamine gauche conformations. Alkylation of the prototype pyridylamino group in 7 markedly improves both histamine H2-receptor antagonist and gastric acid antisecretory activity so that the resulting agent, 3-amino-5-[2-(ethylamino)-4-pyridyl]-1,2,4-triazole (8), is more active than cimetidine.
Address (URL): http://www.ncbi.nlm.nih.gov/pubmed/6131126