Benzene-Ring P2X4 Antagonist Composition for Selective Chronic Cough Therapy
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Solution Overview
Problem
Current drugs targeting the P2X4 receptor for treating cough and other conditions lack diversity in structure, selectivity, and metabolic stability, with no available treatments inhibiting the P2X4 pathway for chronic cough.
Innovation Solution
Development of a compound containing a benzene ring with specific functional groups and heteroatoms, offering high P2X4 antagonistic activity, good selectivity, and low toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing P2X4 antagonist drugs are used, then P2X4 receptor activity is inhibited, but the drugs have monotonous structure, poor selectivity, and low metabolic stability
Solution Approach 1:
The patent applies parameter changes by systematically varying chemical parameters (substituents, heteroatoms, ring sizes) in the P2X4 antagonist structure. The compound formula includes variable R1-R6 groups that can be different atoms or functional groups, allowing optimization of both antagonistic activity and structural diversity simultaneously.
Solution Approach 2:
The patent creates composite molecular structures combining multiple functional moieties (benzene rings, heteroaryl groups, heterocycloalkyl groups) in a single P2X4 antagonist compound. This composite approach enables the molecule to achieve high selectivity and metabolic stability while maintaining potent antagonistic activity.
2Reliability
If existing P2X4 antagonist drugs are used, then P2X4 receptor activity is inhibited, but the drugs lack selectivity and have poor metabolic stability
Solution Approach 1:
The patent applies local quality by introducing specific heteroatoms (N, O, S) and functional groups at particular positions in the molecular structure. The heteroaryl and heterocycloalkyl groups are strategically placed to interact with specific regions of the P2X4 receptor binding site, achieving high selectivity and improved metabolic stability at critical locations.
Data Source
AI summary
A compound containing a benzene ring as shown in formula I, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, an isotopic compound thereof, a crystal form thereof, a nitrogen oxide thereof, and a solvate thereof or a solvate of the pharmaceutically acceptable salt thereof are provided. The compound has high P2X4 antagonistic activity, good selectivity, low toxicity and good metabolic stability.