Synthesis of 2-imidazolidinylidenepropanedinitrile derivatives as stimulators of gastrointestinal motility.

Article Details

Citation

Copy to clipboard

Sasho S, Obase H, Ichikawa S, Kitazawa T, Nonaka H, Yoshizaki R, Ishii A, Shuto K

Synthesis of 2-imidazolidinylidenepropanedinitrile derivatives as stimulators of gastrointestinal motility.

J Med Chem. 1993 Mar 5;36(5):572-9.

PubMed ID

8496937 [ View in PubMed

]

Abstract

Ranitidine (1), the histamine H2-receptor antagonist, has been previously reported to increase gastric emptying and gastric motility by inhibition of acetylcholinesterase (AChE) and enhancement of acetylcholine (ACh) release. In order to obtain potent gastroprokinetic agents, a new series of ranitidine derivatives (5-32) possessing a nitrogen atom instead of a sulfur atom (B) was synthesized and their AChE inhibitory activity and potentiating action on electrically evoked contractions of guinea pig ileum were evaluated. Modification of substituents R1 and R2 markedly influenced the activities. In particular, compound 19, (1-[2-[[[5-(piperidinomethyl)-2-furanyl]methyl]amino]-ethyl]-2- imidazolidinylidene)propanedinitrile fumarate, showed 20 and 100 times more potent AChE inhibitory activity and potentiating action on the ileal contraction, respectively, than ranitidine. Furthermore, compound 19 (KW-5092) enhanced gastrointestinal motility in anesthetized rabbits along with a negligible histamine H2-receptor blocking activity.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Ranitidine	Acetylcholinesterase	IC 50 (nM)	650	N/A	N/A	Details