Triazole Compounds Modulating RyR Receptors for Calcium Homeostasis
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Solution Overview
Problem
Current therapies for muscular dystrophies, such as Duchenne and Becker muscular dystrophy, are inadequate due to their inability to effectively address the underlying issue of intracellular calcium dysregulation, which leads to muscle fiber necrosis and progressive muscle weakness.
Innovation Solution
Development of new 4-[(phenylthio)alkyl]-1H-1,2,3-triazole compounds that modulate RyR receptors, specifically designed to regulate calcium function in human and animal cells, thereby addressing intracellular calcium dysregulation and improving muscle fiber health.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies for muscular dystrophies are used, then treatment is provided, but intracellular calcium dysregulation is not effectively addressed, leading to muscle fiber necrosis and progressive muscle weakness
Solution Approach 1:
The patent applies parameter changes by developing triazole compounds that specifically modulate the activity of ryanodine receptors (RyR1 and RyR2), altering calcium release parameters from the sarcoplasmic reticulum. These compounds change the functional parameters of calcium channels to restore proper calcium homeostasis in dystrophic muscle cells, directly addressing the calcium dysregulation that current therapies fail to treat.
Solution Approach 2:
The triazole compounds act as intermediary substances that mediate between the pathological state of calcium dysregulation and the desired physiological state. These compounds bind to ryanodine receptors and modulate their function, serving as a chemical intermediary that restores calcium homeostasis without requiring genetic correction or other complex interventions.
2Reliability
If new triazole compounds are developed to modulate RyR receptors, then intracellular calcium homeostasis is improved, but device complexity increases
Solution Approach 1:
The patent employs parameter changes by systematically varying the chemical parameters of triazole compounds (substituents at positions 1 and 4, alkyl chain lengths, aromatic groups) to optimize their binding affinity and modulatory effects on ryanodine receptors. This approach allows tuning of molecular properties to achieve desired calcium regulation while managing structural complexity through rational drug design.
Data Source
AI summary
The present invention relates to 1,2,3-triazoles of formula:useful for improving or restoring the intracellular calcium homeostasis and RyR-calstabin binding function in human and animal cells. The present invention also relates to methods for synthesizing said compounds, to pharmaceutical compositions containing them, and to the use thereof for preventing or treating skeletal muscle, heart and nervous system disorders.