JNTU B.Pharmacy III Year MEDICINAL CHEMISTRY-II Previous Question Paper (February-2022 - R17)

H2 receptor antagonists are competitive inhibitors of histamine at the H2 receptors located on the parietal cells of the gastric mucosa. By blocking these receptors, they effectively inhibit both basal and stimulated gastric acid secretion, including acid production induced by gastrin and acetylcholine. Structurally, these agents typically consist of a heterocyclic ring (such as imidazole in cimetidine, furan in ranitidine, or thiazole in famotidine) connected to a polar, non-basic side chain via a flexible spacer. The polar group, often a guanidine or an amidine derivative, is essential for binding to the receptor, while the ring system provides the necessary hydrophobic interactions for affinity.

The synthesis of cimetidine begins with the reaction of cysteamine hydrochloride with acrylonitrile to produce 2-(2-aminoethylthio)ethylamine. This intermediate is then reacted with methyl isothiocyanate to form a thiourea derivative. Subsequently, the thiourea is treated with methyl iodide to form an S-methylisothiourea intermediate, which is then reacted with methylamine to yield the cyanoguanidine moiety. Finally, this intermediate is condensed with 4-methyl-5-chloromethylimidazole (prepared from 4-methylimidazole, formaldehyde, and hydrochloric acid) to yield cimetidine.