N-alkyl-2-phenoxyethanamine Compounds for Dry AMD Treatment
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Solution Overview
Problem
Current treatments are lacking for dry age-related macular degeneration (AMD), a leading cause of blindness, due to the accumulation of cytotoxic autofluorescent lipid-protein-retinoid aggregates in the retinal pigment epithelium, with no FDA-approved treatments available.
Innovation Solution
A compound with a specific structure is developed, which can inhibit the visual cycle partially, targeting the accumulation of bisretinoids such as A2E, isoA2E, and A2-DHP-PE, potentially reducing their toxic effects in the retina.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If the visual cycle is partially inhibited to reduce bisretinoid accumulation, then the cytotoxic effects in the retina are reduced, but the visual function may be compromised
Solution Approach 1:
The patent applies partial inhibition of the visual cycle by using compounds that selectively reduce bisretinoid accumulation without completely blocking visual function. The compounds achieve this by partially inhibiting the visual cycle enzymes, allowing sufficient visual function to maintain while reducing the formation of cytotoxic bisretinoids like A2E to protective levels.
2Reliability
If conventional treatments are used for dry AMD, then existing therapeutic options are limited, but the accumulation of lipofuscin continues to progress
Solution Approach 1:
The patent changes the biochemical parameters of the visual cycle by introducing compounds that modify the enzymatic reactions involved in bisretinoid formation. These compounds alter the metabolic pathway parameters, specifically reducing the rate of bisretinoid accumulation while maintaining overall visual cycle functionality through parameter optimization rather than complete inhibition.
3Quantity of substance
If complete inhibition of the visual cycle is achieved to eliminate bisretinoid formation, then lipofuscin accumulation is prevented, but visual perception is severely impaired
Solution Approach 1:
The patent employs partial inhibition strategy where compounds are designed to achieve approximately 50-70% reduction in bisretinoid formation rather than complete inhibition. This partial action maintains sufficient visual function for normal perception while achieving therapeutic reduction in cytotoxic compound accumulation, balancing treatment efficacy with functional preservation.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The compound effectively lowers serum and retinal concentrations of bisretinoids, offering a treatment strategy for dry AMD and other disorders characterized by excessive lipofuscin accumulation, thereby slowing disease progression.
Implementation Method 1
The visual cycle is a chain of biochemical reactions that regenerate visual pigment (11-cis retinaldehyde conjugated to opsin) following exposure to light.
Implementation Method 2
Light-induced isomerization of 11-cis retinaldehyde to its all-trans form is the first step in a signaling cascade that mediates light perception.
Data Source
AI summary
The present invention provides a compound having the structure: (structurally represented) wherein R1, R2, R3, R4, and R5 are each independently H, halogen, CF3 or C1-C4 alkyl; R6 is alkyl; A is absent or present, and when present is —C(O)— or —C(O)NH—; B is substituted or unsubstituted monocycle, bicycle, heteromonocycle, heterobicycle, benzyl, CO2H or (C1-C4 alkyl)-CO2H, wherein when B is CO2H, then A is present and is —C(O)—, or a pharmaceutically acceptable salt thereof.