Amyloid-Binding Compounds with H-Bond Patterns for Brain Penetration
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Solution Overview
Problem
Current treatments for diseases associated with amyloid or amyloid-like proteins, such as Alzheimer's disease and ocular diseases, lack effective methods to target and prevent amyloid plaque formation, and existing compounds face challenges in crossing the blood-brain barrier and have undesirable side effects.
Innovation Solution
Development of compounds with a specific H-bond donor/acceptor pattern that complements β-sheet structures, facilitating binding to amyloid proteins and enhancing penetration of the blood-brain barrier, while being pharmaceutically acceptable and stable.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing compounds are used to treat amyloid-related diseases, then treatment is provided, but the compounds fail to effectively cross the blood-brain barrier and have undesirable side effects
Solution Approach 1:
The patent applies parameter changes by systematically modifying the chemical structure of compounds, specifically adjusting the H-bond donor/acceptor patterns and molecular properties to optimize both blood-brain barrier penetration and amyloid binding affinity. This involves changing parameters such as molecular weight, lipophilicity, and hydrogen bonding capacity to achieve the desired balance between efficacy and safety
Solution Approach 2:
The invention applies local quality by designing compounds with specific localized H-bond donor and acceptor groups positioned to complement the β-sheet structure of amyloid proteins. This localized functional arrangement allows the compounds to selectively bind to amyloid plaques in the brain while maintaining overall molecular properties that facilitate blood-brain barrier crossing and reduce systemic side effects
2Reliability
If compounds with high affinity for amyloid proteins are designed, then amyloid binding is enhanced, but blood-brain barrier penetration is reduced
Solution Approach 1:
The patent resolves this contradiction by carefully balancing multiple molecular parameters. The compounds are designed with optimized molecular weight (typically 200-500 Da), appropriate lipophilicity (logP values in a specific range), and controlled hydrogen bonding capacity. These parameter adjustments ensure that the compounds can diffuse through the blood-brain barrier while maintaining sufficient affinity for amyloid proteins through their H-bond donor/acceptor patterns
Solution Approach 2:
The invention employs composite molecular structures that combine hydrophobic regions for membrane penetration with polar H-bond donor/acceptor groups for amyloid binding. This composite design allows different parts of the molecule to perform different functions: the hydrophobic portions facilitate blood-brain barrier crossing while the polar regions provide specific binding to the β-sheet structure of amyloid proteins
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 compounds effectively inhibit amyloid aggregation, providing improved treatment options for amyloid-related diseases, including Alzheimer's and ocular conditions, with enhanced brain penetration and reduced side effects.
Implementation Method 1
compounds with a specific H-bond donor/acceptor pattern that complements β-sheet structures, facilitating binding to amyloid proteins
Data Source
AI summary
The present invention relates to novel compounds of formula (II) that can be employed in the treatment of a group of disorders and abnormalities associated with amyloid protein, such as Alzheimer's disease, and of diseases or conditions associated with amyloid-like proteins. The compounds of the present invention can also be used in the treatment of ocular diseases associated with pathological abnormalities/changes in the tissues of the visual system. The present invention further relates to pharmaceutical compositions comprising these compounds and to the use of these compounds for the preparation of medicaments for treating, or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins. A method of treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins is also disclosed.