Quaternary pilocarpine derivatives as potential acetylcholine antagonists. 2. Alterations in the lactone and imidazole moieties

Abstract

In order to investigate the chemical behavior of pilocarpine, as well as the factors which determine its pharmacological activity, systematic and specific structural changes involving the lactone and imidazole moieties have been performed. Series of model compounds with cyclic or open-chain structures and a variety of N-3 bonded chains obtained from previously prepared anticholinergic derivatives of pilocarpine have been synthesized. The changes included N-3 chains of different lengths with an acetylcholine-like structure, the introduction of nucleophilic groups such as ketoxime, hydroxamic, or both at the side chain, or following hydroxylaminolysis of the lactone, respectively. Specific structural alterations could be obtained by reacting with free hydroxylamine under carefully controlled conditions, and the existence of syn and anti isomers was disclosed in certain cases. The new groups in the pilocarpine derivatives influenced their degree of antagonism to acetylcholine. Several compounds displayed some antidotal activity.

Synthesis of 2-Aryl-4,5-diphenyl-1-(N-β-D-glucopyranosyl)imidazoles

“…At the same time, the imidazole fragment appears in a number of naturally occurring products, among which the most important are amino acid histidine, [7] purines, [8] biotin, [9] hydantoin, [10] pilocarpine. [11] The cellular level carbohydrates plays a key role in signaling and targeting of the organic molecule to act on the enzyme's active site. Thus, N-glucosides, i.e.…”

Estudo quimico e farmacologico de alcaloide secundario de Pilocarpus microphyllus Stapf

“…A pilocarpina é clinicamente utilizada para relaxamento intestinal após Iaparotomia (TSURUMI et al 16…”