Delving into the Latest Updates on YM-46303 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

M3 receptor

Mechanism

M3 receptor antagonists(Muscarinic acetylcholine receptor M3 antagonists)

Therapeutic Areas

Urogenital Diseases

Active Indication-

Inactive Indication

Urinary Incontinence

Originator Organization

Astellas Pharma, Inc.

Active Organization-

Inactive Organization

Yamanouchi Pharmaceutical Co. Ltd. /Over-the-Counter Phar Bus

Astellas Pharma, Inc.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC20H22N2O2

InChIKeyXHIQZUNDUKHSQA-UHFFFAOYSA-N

CAS Registry171723-79-8

View All Structures (2)

A novel series of biphenylylcarbamate derivatives were synthesized and evaluated for binding to M1, M2 and M3 receptors and for antimuscarinic activities. Receptor binding assays indicated that biphenyl-2-ylcarbamate derivatives had high affinities for M1 and M3 receptors and good selectivities for M3 receptor over M2 receptor, indicating that the biphenyl-2-yl group is a novel hydrophobic replacement for the benzhydryl group in the muscarinic antagonist field. In this series, quinuclidin-4-yl biphenyl-2-ylcarbamate monohydrochloride (8l, YM-46303) exhibited the highest affinities for M1 and M3 receptors, and selectivity for M3 over M2 receptor. Compared to oxybutynin, YM-46303 showed approximately ten times higher inhibitory activity on bladder pressure in reflexly-evoked rhythmic contraction, and about 5-fold greater selectivity for urinary bladder contraction against salivary secretion in rats. Moreover, selective antagonistic activity was also observed in vitro. Further evaluation of antimuscarinic effects on bradycardia and pressor in pithed rats, and on tremor in mice, showed that YM-46303 can be useful for the treatment of urinary urge incontinence as a bladder-selective M3 antagonist with potent activities and fewer side effects.

100 Deals associated with YM-46303

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