Heteroaromatic Compounds Targeting Alpha-Synuclein Oligomers
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Solution Overview
Problem
Current compounds fail to specifically target and block the formation of propagating dimers and toxic alpha-synuclein oligomers, which are central to the pathogenesis of synucleopathies such as Parkinson's Disease and related conditions, despite their potential role in neurodegenerative processes.
Innovation Solution
Development of organic heteroaromatic compounds with a central heteroaromatic ring structure linked to specific moieties, which selectively bind misfolded alpha-synuclein and prevent the aggregation of oligomers, thereby blocking the formation of propagating dimers and toxic species.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing compounds are used to treat synucleopathies, then general neuroprotective effects may be achieved, but specific blocking of propagating dimer formation and toxic oligomer aggregation is not accomplished
Solution Approach 1:
The patent applies local quality by designing compounds with specific molecular features (heteroaromatic ring structure with particular substituents) that are selectively attracted to misfolded alpha-synuclein propagating dimers and toxic oligomers. The compound's molecular structure includes a heteroaromatic ring (R1-R3 positions) with specific linkages (L, W) that create localized chemical affinity for the pathological alpha-synuclein species, enabling selective binding without affecting normal neuronal functions.
Solution Approach 2:
The patent utilizes parameter changes by systematically varying the molecular parameters of the compound structure - specifically the heteroaromatic ring substituents (R1, R2, R3 groups), linkage types (L: NHCO, O, S, NHCONH, NHCOO), and alkyl chain lengths (W: 1-6 carbon atoms). These parameter variations create a series of compounds with different binding affinities and specificities for alpha-synuclein oligomers, allowing optimization for therapeutic effectiveness.
2Reliability
If compounds are designed to improve dopaminergic neurotransmission, then Parkinson's disease symptoms may be managed, but the formation of toxic oligomers is not directly addressed
Solution Approach 1:
The patent applies segmentation by dividing the compound into distinct functional segments: a heteroaromatic ring core (R1-R3), linkage groups (L: NHCO, O, S, NHCONH, NHCOO), and alkyl side chains (W: 1-6 carbon atoms). This segmentation allows each part to perform its specific function - the heteroaromatic ring binds to alpha-synuclein, the linkages provide structural flexibility and binding orientation, and the alkyl chains modulate membrane interaction and cellular uptake.
Solution Approach 2:
The patent introduces the heteroaromatic compound as an intermediary substance that mediates between the toxic alpha-synuclein oligomers and healthy neuronal cells. The compound binds to propagating dimers and toxic oligomers, preventing their further aggregation and neurotoxic effects, while the heteroaromatic structure itself serves as the mediating agent that translates the pathological state into a controllable molecular interaction.
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
These compounds effectively inhibit the formation of toxic alpha-synuclein oligomers, offering a potential therapeutic approach to treat and prevent synucleopathies by targeting the root cause of neurodegeneration in diseases like Parkinson's Disease.
Implementation Method 1
These compounds bind selectively misfolded SYN and prevent aggregation of oligomers into toxic species
Data Source
AI summary
The present invention relates to a compound of formula (I): Wherein R1 is a substituted or unsubstituted aromatic hetero- or homocyclic or a substituted or unsubstituted alicyclic hetero- or homocyclic group; R2 is an alkyl group with 1 to 18 carbon atoms or a substituted or unsubstituted cycloalkyl or aryl group; R3 is a substituted or unsubstituted aromatic hetero- or homocyclic or a substituted or unsubstituted alicyclic hetero- or homocyclic group; L is a single bond, an alkyl group having 1 to 6 carbon atoms, NHCO, O, S, NHCONH or NHCOO; X, Y and Z are independently O, N, NH, S or CH; W is a single bond or an alkyl group having from 1 to 6 carbon atoms; or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate of said compound or salt.