Ester-Containing Aromatic Propionamide for Cardiac Function and Fibrosis

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Solution Overview

Problem

Existing treatments for heart failure do not effectively address the reduction in ejection fraction, fractional shortening, and cardiac output, and the progression of myocardial fibrosis leads to worsening heart function.

Innovation Solution

The use of the ester group-containing aromatic propionamide compound (S)-1-((4-cyano-3-(trifluoromethyl)phenyl)amino)-3-(4-cyanophenoxy)-2-methyl-1-oxopropan-2-yl nicotinate, administered at doses of 1 mg/kg to 10 mg/kg, particularly 3 mg/kg, to treat heart failure.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional treatments for heart failure are used, then existing therapy protocols are maintained, but ejection fraction, fractional shortening, and cardiac output continue to deteriorate

Engineering Contradiction:
Improvecardiac functionVSAvoidejection fraction
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent applies parameter changes by modifying the chemical structure of propionamide compounds to optimize cardiac function. Specifically, the compound incorporates a fluorinated aromatic ring system with specific substituent patterns (cyano and trifluoromethyl groups) that enhance binding affinity to cardiac targets, thereby improving ejection fraction and cardiac output parameters in heart failure treatment

Inventive Principle:
Principle #35Parameter changes

2Strength

If myocardial fibrosis progresses to repair injured tissues, then collagen production increases, but left ventricular compliance decreases and heart function deteriorates

Engineering Contradiction:
Improvetissue repairVSAvoidleft ventricular compliance
Core Design Contradiction:
StrengthVSStability of the object's composition

Solution Approach 1:

The patent converts the harmful effect of excessive collagen deposition into a beneficial outcome by using the propionamide compound to modulate fibrosis progression. The compound selectively promotes organized collagen remodeling that maintains tissue strength while preserving ventricular compliance, thereby transforming the pathological fibrotic process into a reparative one

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Data Source

PatentEP4212158B1(s)-1-((4-cyano-3-(trifluoromethyl)phenyl)amino)-3-(4-cyanophenoxy)-2-methyl-1-oxopropan-2-yl nicotinate for use in the treatment of heart failure
Publication Date: 2025.10.22 CHANGCHUN GENESCIENCE PHARM CO LTD
  • EP4212158B1 patent drawingFigure 1~2
  • EP4212158B1 patent drawingFigure 3~5
  • EP4212158B1 patent drawingFigure 6~8

AI summary

An application of an ester group-containing aromatic propionamide compound and a metabolite thereof in preparation of a drug for treating heart failure. The ester group-containing aromatic propionamide compound is C25H17F3N4O4. The ester group-containing aromatic propionamide compound can improve the situation of reduction in ejection fraction, fractional shortening and cardiac output of a chronic heart failure rat, and increase LVSP of a heart failure rat.