Deuterium-Enriched Compounds Stabilize TTR to Prevent Amyloidosis
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Solution Overview
Problem
Current treatments for transthyretin amyloidosis (ATTR) and related diseases are inadequate, as existing drugs cannot effectively prevent the misfolding, aggregation, and deposition of amyloid fibrils in organs and tissues, leading to progressive and potentially fatal conditions.
Innovation Solution
Development of novel deuterium-enriched compounds that stabilize the tetrameric structure of transthyretin (TTR), preventing its dissociation and subsequent aggregation, thereby treating ATTR and related diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing drugs are used to treat transthyretin amyloidosis, then treatment is provided, but the drugs cannot effectively prevent misfolding, aggregation, and deposition of amyloid fibrils
Solution Approach 1:
The patent applies parameter changes by substituting hydrogen atoms with deuterium atoms in the chemical structure of the compound. This isotopic substitution alters the physical and chemical properties of the molecule, specifically enhancing its ability to stabilize transthyretin and prevent amyloid fibril formation, thereby improving treatment effectiveness while reducing harmful effects
Solution Approach 2:
The patent employs composite materials by creating a deuterated version of the compound (diflunisal-d14) that combines the parent compound's pharmacological activity with enhanced stability properties. The deuterated compound acts as a composite structure where deuterium atoms are integrated into the molecular framework to provide superior therapeutic effects compared to the non-deuterated version
2Stability of the object's composition
If transthyretin tetramer structure is not stabilized, then natural protein function is maintained, but dissociation and misfolding occur leading to amyloid formation
Solution Approach 1:
The deuterated compound exerts preliminary anti-action by preemptively binding to transthyretin and stabilizing its tetrameric structure before dissociation and misfolding can occur. This preventive stabilization blocks the pathway to amyloid fibril formation, addressing the contradiction by maintaining protein stability while preventing harmful amyloid generation
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 deuterium-enriched compounds effectively stabilize TTR, inhibiting its misfolding and aggregation, which in turn prevents the deposition of amyloid fibrils in various organs and tissues, offering a promising therapeutic approach for ATTR and related diseases.
Implementation Method 1
novel deuterium-enriched compounds that stabilize the tetrameric structure of transthyretin (TTR), preventing its dissociation
Implementation Method 2
inhibiting its misfolding and aggregation, which in turn prevents the deposition of amyloid fibrils
Data Source
AI summary
The present invention is concerned with novel deuterium-enriched compounds of the general chemical structural formula I, and pharmaceutically acceptable salts, compositions, and methods of use thereof, wherein, R is independently deuterium (D), hydrogen (H) atom. Compounds of the general chemical structure formula I are stabilizers of the Transthyretin (TTR) protein and are useful in the treatment of Transthyretin Amyloidosis cardiomyopathy (ATTR-CM) and Polyneuropathy (ATTR-PN), and related diseases.