Patent Evaluation: The use of Muscarinic Receptor Antagonists for Gastrointestinal Disorders

Summary

Novelty: N-substituted-4-acetoxypiperidines are disclosed and are claimed to be antagonists of the muscarinic acetylcholine receptor (mAChR), and are said to be particularly selective for the M₃-receptor subtype. This receptor subtype subserves gastrointestinal and bronchiolar constriction, hence these agents are potentially useful as spasmolytic and bronchodilatatory agents, yet should not exhibit significant cardiac side-effects.

Biology: The affinity of the agents for cardiac and ileal mAChR was assayed using isolated guinea pig atrium and ileum; the log affinity constants ranged from 4.5-6.5 (atrium) to 6.5-7.5 (ileum), indicating significant selectivity for M₃ receptors.

Chemistry: Synthesis of the compounds was by conventional methods and is fully described, forming a subsidiary part of the claim. Three compounds are specifically claimed, including 1-benzyl-4-diphenylacetoxy-piperidine.

Structure: