Bisamide Sarcomere Activators for Heart Failure
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Solution Overview
Problem
Current therapies for congestive heart failure, such as inotropes, fail to effectively improve cardiac function and are poorly selective for cardiac tissue, leading to adverse effects and limited use, necessitating the development of new agents that exploit different mechanisms of action for improved symptom relief, safety, and patient mortality outcomes.
Innovation Solution
Development of bis-amide compounds that activate the cardiac sarcomere by binding to the Troponin C/Troponin I interface, modulating the activity of the cardiac sarcomere to enhance cardiac function.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current inotrope therapies are used to treat congestive heart failure, then cardiac function may be improved, but selectivity for cardiac tissue is poor leading to adverse effects
Solution Approach 1:
The bis-amide compounds are designed to specifically target the cardiac sarcomere by binding to the Troponin C/Troponin I interface, which is unique to cardiac muscle tissue. This localized action at the cardiac sarcomere level provides high tissue selectivity, improving cardiac function without the adverse effects associated with non-selective inotropes that affect multiple tissue types.
2Reliability
If current inotrope therapies are used, then some cardiac benefit may be achieved, but effectiveness is limited and safety profile is poor
Solution Approach 1:
The bis-amide compounds act as intermediary molecules that specifically bind to the Troponin C/Troponin I interface, a unique cardiac sarcomere structure. This intermediary binding mechanism provides highly selective activation of cardiac contraction without the harmful off-target effects of current inotropes, thereby improving both effectiveness and safety profile for treating congestive heart failure.
Data Source
AI summary
The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising a compound of the invention, a method for manufacturing compounds of the invention and therapeutic uses thereof.