Thiazole Diphenyl Sulfoxides for Selective DAT Inhibition
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Solution Overview
Problem
Existing cognitive enhancers targeting the dopamine transporter (DAT) lack specificity, leading to unsatisfactory improvements in learning and memory functions and often cause severe side effects due to non-specific inhibition of noradrenaline and serotonin transporters.
Innovation Solution
Development of diastereomeric compounds, specifically diastereomerically enriched or pure compounds with a thiazole and diphenyl substituted sulfoxide structure, which selectively target the dopamine transporter to enhance extracellular dopamine concentrations, thereby improving learning and memory functions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If existing dopamine transporter inhibitors are used to improve cognitive functions, then learning and memory performance is enhanced, but severe side effects occur due to lack of specificity
Solution Approach 1:
The patent applies local quality by designing compounds with specific molecular structures (thiazole and diphenyl substituted sulfoxides with particular stereochemistry) that target only the dopamine transporter. This structural specificity ensures the drug acts locally on DAT without affecting other transporters like noradrenaline and serotonin transporters, thereby enhancing cognitive function while minimizing side effects.
Solution Approach 2:
The patent utilizes asymmetry by developing diastereomerically enriched or pure compounds rather than racemic mixtures. The specific stereochemical configuration (e.g., (R)- or (S)-enantiomers) provides asymmetric interaction with the dopamine transporter, improving both efficacy and selectivity. This asymmetric design allows the compound to fit precisely into the DAT binding site while avoiding off-target effects on other transporters.
2Quantity of substance
If non-specific dopamine transporter inhibitors are used, then extracellular dopamine concentration increases, but noradrenaline and serotonin transporters are also inhibited causing psychiatric disorders
Solution Approach 1:
The patent applies parameter changes by modifying molecular parameters such as stereochemistry, substitution patterns on phenyl rings, and thiazole ring positioning. These parameter changes result in compounds with optimized binding affinity for DAT while reducing affinity for other transporters. The specific structural parameters ensure selective increase of extracellular dopamine without affecting noradrenaline and serotonin levels, preventing psychiatric side effects.
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 provide enhanced learning and memory capabilities, particularly spatial memory, with reduced side effects by selectively increasing dopamine levels without affecting other neurotransmitters.
Implementation Method 1
The dopamine transporter reuptakes extracellular dopamine into the synapse, and inhibitors increase the extracellular concentration of dopamine
Data Source
AI summary
The present disclosure relates to a chemical compound having the general formula (I):wherein R1 is a phenyl group and R2 is a meta-substituted phenyl group; and RTA is a substituted or unsubstituted thiazole ring. The disclosure also relates to said compound according to formula (I), in particular in its diastereomerically pure or enriched form, for use in therapy, in particular for treating and/or preventing age-related cognitive decline. Further, the disclosure relates to said compound according to formula (I) for use in improving cognitive functions, in particular for use in improving the spatial learning capabilities in human individuals. And, disclosure also relates to said compound according to formula (I) for use in the treatment and/or prevention of alcohol addiction, nicotine addiction and/or drug addiction, in particular cocaine and/or metamphetamine addiction.