ABC Transporter Modulators via Formula II Compounds
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Solution Overview
Problem
Current treatments for ABC transporter-mediated diseases, such as cystic fibrosis, lack effective modulators to address defective protein trafficking and activity, leading to impaired ion and fluid transport, and there is a need for compounds that can modulate ABC transporter activity to treat various diseases beyond cystic fibrosis.
Innovation Solution
Development of specific compounds with the general formula II and their pharmaceutically acceptable salts, which act as modulators of ABC transporter activity, particularly CFTR, to increase or decrease activity, thereby treating a range of diseases including cystic fibrosis, emphysema, and other secretory and protein folding diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for ABC transporter-mediated diseases are used, then disease management is maintained, but effective modulation of defective protein trafficking and transporter activity is not achieved
Solution Approach 1:
The patent employs parameter changes by developing a series of compounds with varying structural parameters (substituents R1-R6, ring systems, linkers) to modulate ABC transporter activity. The general formula II provides a framework where multiple parameters can be adjusted to optimize binding affinity and functional effects on different ABC transporters, enabling effective treatment of various diseases caused by defective protein trafficking and transporter dysfunction
2Productivity
If ABC transporter activity is not modulated, then current therapeutic approaches are maintained, but ion and fluid transport remains impaired
Solution Approach 1:
The patent uses small molecule compounds as intermediaries that bind to ABC transporters to restore their function. These compounds act as mediators between the defective transporter and normal physiological function, facilitating proper ion and fluid transport by stabilizing transporter conformation, enhancing gating, or improving protein folding and trafficking to the cell membrane
3Adaptability or versatility
If compounds with general formula II are developed, then ABC transporter modulation capability is achieved, but development complexity increases
Solution Approach 1:
The patent achieves universality by designing a general formula II that can modulate multiple ABC transporters (CFTR, MDR1, MRP1, etc.) with a single compound framework. This multi-functional approach allows one compound structure to address different transporter deficiencies underlying various diseases, reducing the need for entirely separate drug development programs for each condition
Data Source
AI summary
Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette ("ABC") transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator ("CFTR"). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.