General Description

4-Morpholineethanesulfonic acid is a vital buffering agent in biochemical research and medicinal chemistry, characterized by its excellent buffering properties within a pH range of 5.5 to 6.7 and a pKa value of 6.10. It plays a significant role in the synthesis of pharmaceutical compounds like 4-{2-[5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yloxy]ethyl}morpholine, enhancing their selectivity and potency. Additionally, 4-Morpholineethanesulfonic acid is essential in pharmacological evaluations, such as its application in neurogenic and neuropathic pain studies, demonstrating dose-dependent effects and favorable safety profiles. Thus, 4-Morpholineethanesulfonic acid is crucial for advancing therapeutic agent development.

Figure 1. 4-Morpholineethanesulfonic acid

Overview

4-Morpholineethanesulfonic acid is a highly effective buffering agent commonly utilized in biochemical and biological research. This compound, characterized by its molecular formula C6H13NO4S and a molecular weight of 195.2 g/mol, exhibits impressive buffering properties, particularly within a pH range of 5.5 to 6.7. The significance of the pKa value of 4-Morpholineethanesulfonic acid, which stands at 6.10 at 25°C, makes it exceptionally valuable for experiments requiring tight pH regulation. Its widespread use stems from several advantageous characteristics, including excellent water solubility, minimal interference with salt ions, and stability at various temperatures. These features are crucial for maintaining consistent experimental conditions, thereby ensuring reliable and reproducible results.

Preparation and Storage

To prepare a buffer solution using 4-Morpholineethanesulfonic acid, one typically adjusts the pH by adding sodium hydroxide or potassium hydroxide to reach the desired pH range of 5.5 to 6.7. Initially, the solution is acidic, with a pH between 2.5 and 5 prior to adjustment, and it displays a colorless and transparent appearance. A saturated solution of 4-Morpholineethanesulfonic acid at 0°C can achieve a concentration of approximately 0.65M, which is substantial for many laboratory applications. For optimal long-term storage, the buffer solution should be maintained at a temperature between 2-8°C and ideally passed through a 0.2-micron filter to eliminate potential contaminants. Although high-temperature sterilization is discouraged due to the risk of yellowing the solution, this discoloration does not significantly impact the pH stability, thus ensuring the compound's effectiveness remains intact for critical research applications. ¹

Applications in Medicinal Chemistry

4-Morpholineethanesulfonic acid plays a significant role in medicinal chemistry, particularly in the development of pharmaceutical compounds. Its importance is highlighted in the synthesis and evaluation of novel compounds such as 4-{2-[5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yloxy]ethyl}morpholine. This compound, also known as S1RA or E-52862, is an example of a σ1 receptor antagonist that has been extensively studied for its therapeutic potential. The presence of 4-Morpholineethanesulfonic acid in the synthesis of this compound demonstrates its utility in creating molecules with targeted biological activity. The incorporation of 4-Morpholineethanesulfonic acid into drug design can influence the compound's binding affinity and selectivity, essential for developing effective pharmaceuticals.

Role in Drug Design and Synthesis

The synthesis of 4-{2-[5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yloxy]ethyl}morpholine involves the strategic use of 4-Morpholineethanesulfonic acid to modify the chemical properties of the pyrazole class of σ1 receptor antagonists. In this synthesis, 4-Morpholineethanesulfonic acid contributes to the formation of a compound with significant selectivity and potency. The chemical structure of the final product benefits from the inclusion of 4-Morpholineethanesulfonic acid, which helps in achieving desired pharmacological profiles. This application highlights the acid's role in enhancing the efficacy and specificity of drug candidates by influencing their interaction with biological targets.

Impact on Pharmacological Research

4-Morpholineethanesulfonic acid's involvement extends beyond synthesis to the pharmacological evaluation of new compounds. For instance, the compound 4-{2-[5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yloxy]ethyl}morpholine, derived using 4-Morpholineethanesulfonic acid, has shown promise in animal models for neurogenic pain and neuropathic pain. The compound exhibited dose-dependent antinociceptive effects and demonstrated favorable physicochemical and safety profiles. This underscores the critical role of 4-Morpholineethanesulfonic acid in optimizing drug candidates, making it a valuable tool in the advancement of medicinal chemistry and the development of effective therapeutic agents. ²