Selective 5-HT2A Antagonist for Platelet Aggregation

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current treatments for serotonin receptor-mediated conditions, such as platelet aggregation and coronary artery disease, lack effective and selective antagonists for the 5-HT2A receptor, which are necessary to prevent or alleviate symptoms like platelet aggregation and ischemic events.

Innovation Solution

Administering a therapeutically effective dose of 4-[3-[4-(6-fluoro-1,2,-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxy-benzoic acid or its pharmaceutically acceptable salt, which acts as a potent antagonist for the 5-HT2A receptor, either alone or in combination with antithrombotic agents, to treat conditions mediated by serotonin receptors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments for serotonin receptor-mediated conditions are used, then general treatment coverage is provided, but effective and selective antagonism of the 5-HT2A receptor is lacking

Engineering Contradiction:
Improveeffectiveness of treatmentVSAvoidselectivity for 5-HT2A receptor
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies parameter changes by modifying the chemical structure parameters of the compound to achieve optimal binding affinity and selectivity for the 5-HT2A receptor. The specific molecular structure with defined substituents (R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12) allows precise tuning of receptor interaction parameters, enabling selective antagonism while maintaining therapeutic effectiveness.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If a potent 5-HT2A receptor antagonist is administered, then platelet aggregation and ischemic events are inhibited, but brain penetration may cause unwanted central effects

Engineering Contradiction:
Improveinhibition of platelet aggregationVSAvoidcentral nervous system side effects
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by designing a compound with specific physicochemical properties that enable selective distribution to peripheral tissues (platelets, vasculature) while limiting penetration into the central nervous system. The molecular structure is optimized to have appropriate lipophilicity and molecular weight characteristics that favor peripheral target engagement over blood-brain barrier crossing, thereby achieving local therapeutic action with minimal central side effects.

Inventive Principle:
Principle #3Local quality

Data Source

PatentUS9987264B2Method and composition for treating a serotonin receptor-mediated condition
Publication Date: 2018.06.05 VANDA PHARMACEUTICALS INC

AI summary

A method and composition for treating serotonin receptor-mediated conditions.