Cyclized Arylcyclohexylamine Derivatives for Higher Brain Bioavailability
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Solution Overview
Problem
Existing synthesis methods for ketamine and its metabolites, such as norketamine and 6-hydroxynorketamine, are limited in variability and flexibility, resulting in highly polar derivatives with low bioavailability and rapid excretion, making them unsuitable for effective treatment of neurodegenerative and mental disorders.
Innovation Solution
A process involving a cyclization reaction to convert aromatic acrylic acid derivatives into cyclic 3-ene-2-oxy-1-carboxylic acid derivatives, allowing the production of structurally diverse cyclic 2-amino-1-one derivatives, including 2-aminocyclohexan-1-one and 2-aminocyclohexen-1-one derivatives, with improved bioavailability and reduced polarity, facilitating their use as active pharmaceutical ingredients.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If existing synthesis methods are used to prepare ketamine derivatives, then the synthesis process is simple, but the derivatives obtained are highly polar with low bioavailability and rapid excretion
Solution Approach 1:
The patent introduces a cyclization reaction parameter change that transforms linear aromatic acrylic acid derivatives into cyclic 2-amino-1-one derivatives. This structural parameter change fundamentally alters the molecular properties, reducing polarity and enhancing bioavailability while maintaining synthetic accessibility through the cyclization process
2Ease of manufacture
If existing synthesis methods are used to prepare ketamine derivatives, then the synthesis process is straightforward, but the derivatives exhibit rapid excretion and reduced therapeutic efficacy
Solution Approach 1:
The cyclization reaction fundamentally changes the molecular parameter from linear to cyclic structure, which alters pharmacokinetic properties. The cyclic 2-amino-1-one structure reduces polarity and increases molecular stability, thereby reducing excretion rate and extending duration of action for therapeutic applications
3Ease of manufacture
If highly polar ketamine derivatives are produced, then they can be synthesized using conventional methods, but they show low bioavailability and reduced efficacy in treating neurodegenerative and mental disorders
Solution Approach 1:
The patent applies a cyclization reaction that changes the fundamental structural parameter from linear to cyclic, transforming highly polar derivatives into less polar cyclic 2-amino-1-one derivatives. This parameter change maintains synthetic feasibility while dramatically improving therapeutic efficacy for neurodegenerative and mental disorders through enhanced blood-brain barrier penetration
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 process enables the production of a wide range of ketamine derivatives with enhanced bioavailability and reduced polarity, improving their efficacy in treating neurodegenerative and mental disorders by facilitating uptake through the blood-brain barrier and reducing side effects like urinary bladder toxicity.
Implementation Method 1
a cyclization reaction, in particular a [4+2]-cycloaddition, in particular a Diels-Alder reaction
Data Source
AI summary
The present invention relates to the technical field of pharmaceutical synthesis and development of drugs, and to a process for preparing cyclic 2-amino-1-one derivatives and to the reaction products and intermediates obtainable by this process. The present invention further relates to pharmaceutical compositions, in particular drugs or medicaments, comprising the cyclic 2-amino-1-one derivatives and to their use as medicaments, in particular in the prophylactic or therapeutic treatment of diseases of the human or animal body, preferably of neurodegenerative diseases or psychiatric disorders.