Thioether MDMA Analogs for Shorter Therapeutic Duration
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Solution Overview
Problem
The duration of action of racemic 3,4-methylenedioxymethamphetamine (rac-MDMA) is not ideal for therapeutic administration, lasting approximately 4-6 hours, necessitating the development of shorter-acting MDMA analogs that maintain therapeutic benefits.
Innovation Solution
Novel thioether-containing MDMA analogs are developed, featuring a metabolically labile thioether group that mimics the methylenedioxy ring, leading to rapid enzymatic oxidation and decreased duration of action, with specific compounds including 2H-1,3-benzoxathiole and benzthiophene derivatives.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If rac-MDMA is used for therapeutic administration, then therapeutic benefits are achieved, but the duration of action is too long (4-6 hours)
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of MDMA through substitution of the methylenedioxy group with thioether-containing groups (benzoxathiole, benzothiophene). This structural parameter change results in altered pharmacokinetic properties, specifically rapid metabolic inactivation and shortened duration of action, while maintaining therapeutic efficacy for conditions like PTSD
Solution Approach 2:
The invention creates short-acting MDMA analogs that are rapidly metabolized and inactivated in the body. These compounds function as 'short-living' therapeutic agents that provide their effect quickly and then are rapidly cleared, avoiding the prolonged duration of action of rac-MDMA. This is achieved through the metabolically labile thioether groups that are rapidly oxidized in vivo
2Duration of action of moving object
If shorter-acting MDMA analogs are developed, then duration of action is reduced, but metabolic stability is compromised
Solution Approach 1:
The patent intentionally changes the metabolic stability parameter by incorporating thioether groups into the MDMA structure. These thioether-containing analogs (with benzoxathiole or benzothiophene groups) are designed to be metabolically labile, undergoing rapid oxidative metabolism to produce inactive metabolites, thereby achieving short duration of action while maintaining controlled metabolic behavior
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 novel compounds exhibit increased metabolic inactivation, resulting in a shorter duration of action, providing more convenient therapeutic effects for conditions like PTSD and other psychological disorders.
Implementation Method 1
The sulfur position of the thioether can be oxidized after ingestion by a subject, by an oxygenase or peroxidase enzyme, to form a sulfone that may more rapidly be metabolically degraded into an inactive metabolite
Data Source
AI summary
The present invention is directed to novel chemical compositions of matter, and in particular novel MDMA class of compounds having substituted methylenedioxyphenethylamine and substituted amphetamine, having a metabolically labile thioether group.