Hydrochloride Salt Morpholine Sigma Receptor Stability
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Solution Overview
Problem
Current forms of 4-[2-[[5-methyl-1-(2-naphthalenyl)-1H-pyrazol-3-yl]oxy]ethyl]morpholine lack enhanced thermodynamic stability, purity, and bioavailability, which hinders its pharmaceutical development and therapeutic efficacy, particularly in the treatment of sigma receptor-mediated diseases.
Innovation Solution
The hydrochloride salt of 4-[2-[[5-methyl-1-(2-naphthalenyl)-1H-pyrazol-3-yl]oxy]ethyl]morpholine, with a molecular weight of 373.88 and a pKa of 6.73, is developed, offering improved solubility, absorption, and stability, facilitating better pharmaceutical formulations and therapeutic effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the free base form of 4-[2-[[5-methyl-1-(2-naphthalenyl)-1H-pyrazol-3-yl]oxy]ethyl]morpholine is used, then the compound can be synthesized directly, but it lacks enhanced thermodynamic stability, purity, and bioavailability
Solution Approach 1:
The patent applies parameter changes by converting the free base form of the compound into its hydrochloride salt form. This chemical modification changes the physical and chemical parameters of the compound, resulting in enhanced thermodynamic stability, improved purity, and better bioavailability while maintaining the core pharmacological activity of the original molecule.
Solution Approach 2:
The invention creates a composite form by combining the active pharmaceutical ingredient with hydrochloric acid to form a salt. This composite material (hydrochloride salt) integrates the benefits of both the original compound and the acid, providing improved stability and solubility characteristics that neither component possesses alone.
2Ease of operation
If alternative forms of the compound are developed to improve solubility and absorption, then therapeutic efficacy is enhanced, but the manufacturing and handling complexity increases
Solution Approach 1:
By changing the chemical form from free base to hydrochloride salt, the patent improves solubility and absorption parameters. The salt form exhibits better dissolution characteristics and bioavailability, directly addressing the ease of operation requirement while the straightforward salt formation process maintains manufacturing simplicity.
3Ease of operation
If the hydrochloride salt form is used, then solubility, absorption, and stability are improved, but the molecular weight increases from 337.42 to 373.88
Solution Approach 1:
The patent accepts the increase in molecular weight as a necessary trade-off for achieving significant improvements in solubility, absorption, and stability. The hydrochloride salt formation adds only 36.46 Da (the mass of HCl) to the original molecule, which is a minimal increase compared to the substantial gains in pharmacokinetic properties.
4Reliability
If selective sigma-1 receptor antagonist forms are developed, then therapeutic effects are enhanced, but the complexity of achieving desired pharmacological properties increases
Solution Approach 1:
The hydrochloride salt form serves multiple functions simultaneously: it maintains the selective sigma-1 receptor antagonist activity, enhances solubility and absorption, improves thermodynamic stability, and facilitates pharmaceutical formulation. This multi-functional form eliminates the need for separate optimizations of each property.
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 hydrochloride salt exhibits enhanced solubility and absorption profiles, leading to improved therapeutic effects and stability, making it suitable for the treatment and prophylaxis of various sigma receptor-mediated diseases with reduced side effects and improved handling and storage characteristics.
Implementation Method 1
The compound has a molecular weight 337.42 uma... The hydrochloride salt exhibits enhanced solubility and absorption profiles
Data Source
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AI summary
The present invention relates to 4-[-2-[[5-methyl-1 -(2-naphthalenyl)-1 H-pyrazol-3- yl]oxy]ethyl]morpholine salts, specifically to the hydrochloride, to pharmaceutical compositions comprising them, and to their use in therapy and/or prophylaxis of sigma receptor associated diseases.