Fluorophenyl Substituted Muscarinic Receptor Ligands with Selectivity for M3 over M2

Simple SummaryContent extracted from patent full text and abstract with AI.

This patent describes a new class of fluorophenyl-substituted compounds that selectively bind to the M3 subtype of the human muscarinic acetylcholine receptor over the M2 subtype. These compounds act as antagonists, meaning they block the activity of the M3 receptor, which is predominantly found in the airway smooth muscles and mucosal glands, and is involved in mediating bronchoconstriction and mucus secretion. The compounds are intended for use as treatments for diseases such as asthma, chronic obstructive pulmonary disease (COPD), bronchopulmonary dysplasia (BPD), and urinary incontinence. The key innovation is their high selectivity for the M3 receptor, minimizing unwanted effects on the M2 receptor (which is mainly present in the heart), and this selectivity is achieved using a fluorine substitution on the phenyl ring of the molecule.

Use CasesContent extracted from patent full text and abstract with AI.

• Treatment of asthma by relaxing airway smooth muscles to ease breathing.
• Treatment of chronic obstructive pulmonary disease (COPD) by reducing bronchoconstriction and mucus secretion.
• Management of bronchopulmonary dysplasia (BPD), especially in premature infants with lung development problems.
• Treatment of urinary incontinence by modulating smooth muscle contraction in the bladder.
• Potential treatment for other diseases involving M3 receptor activity, such as chronic bronchitis, bronchiectasis, chronic airway obstruction, pulmonary fibrosis, pulmonary emphysema, allergic rhinitis, and possibly cognitive disorders.

BenefitsContent extracted from patent full text and abstract with AI.

• High selectivity for the M3 receptor subtype reduces unwanted side effects related to M2 receptor antagonism (e.g., less risk of cardiovascular effects).
• Improved potency and specificity mean lower doses may be required, potentially increasing patient safety.
• Reduction of side effects typically associated with less selective muscarinic antagonists, leading to better patient compliance and quality of life.
• Broad spectrum of potential applications across multiple respiratory and urinary diseases.
• Supports use in both acute and chronic management of relevant conditions due to favorable pharmacological profile (e.g., long receptor residence time observed for lead compounds).

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Patent Abstract

The present invention relates to fluorophenyl substituted muscarinic receptor ligands with selectivity for M3 over M2 and to the use of these compounds in the treatment of various diseases such as asthma, chronic obstructive pulmonary disease (COPD), bronchopulmonary dysplasia (BPD) and urinary incontinence.