Sulfapyridine

Rani P, et al. Medical Hypotheses, 2022, 165, 110896.

Sulfapyridine, an active moiety derived from sulfasalazine, holds significant potential for the treatment of rheumatoid arthritis (RA). However, traditional formulations necessitate high doses (2-3 g/day), resulting in adverse effects including agranulocytosis, hematuria, and psychosis. Additionally, sulfapyridine's biphasic solubility in water (268 mg/L) and n-octanol (243.3 mg/L) presents significant formulation challenges.
Self-assembling prodrugs offer a promising alternative. These amphiphilic molecules spontaneously form nanostructures, creating a built-in delivery system. These structures improve pharmacokinetics by extending circulation time, reducing renal clearance, and increasing drug accumulation at target sites. The encapsulation also protects sulfapyridine from degradation, enhancing stability during storage and administration. In comparative studies, self-assembling prodrug systems demonstrated superior therapeutic profiles compared to liposomal formulations, which are often hindered by complex preparation, instability, and cost inefficiencies. Prodrugs designed with flexible polyunsaturated fatty acid chains exhibited enhanced assembly and improved therapeutic efficacy. Furthermore, dual drug-loaded self-assembling hydrogels enabled controlled release and synergistic therapeutic effects.

Saini A, et al. Journal of Organometallic Chemistry, 2019, 893, 32-38.

Sulfapyridines can be used to prepare multifunctional electrochemical sensing materials [sulfapyridine-H]+[Co(C2B9H11)2]-. The synthesis of [Sulfapyridine-H]+[Co(C2B9H11)2]-, a novel electroactive salt, demonstrates its applicability in potentiometric detection of sulfonamides.
The salt [Sulfapyridine-H]+[Co(C2B9H11)2]- was synthesized through a two-step process. Cs[3,3'-Co(1,2-closo-C2B9H11)2] was extracted using aqueous HCl and diethyl ether. After removing diethyl ether, the residue was diluted to a 0.05 M solution. Simultaneously, Sulfapyridine was dissolved in water with minimal HCl to prepare a 0.05 M acid solution. Mixing these solutions yielded a yellow precipitate, which was isolated and purified under vacuum.
The composition of the synthesized salt was confirmed by 1H NMR spectroscopy, where the integration of metallacarborane and Sulfapyridine proton signals revealed a stoichiometry consistent with a 1:1 salt. This indicates successful complex formation, crucial for its intended electrochemical applications.

Kapoor B, et al. Materials Science and Engineering: C, 2021, 118, 111332.

Sulfapyridine (SP) serves as a precursor in the synthesis of its amide prodrug (SP-PD). The synthesis of SP-PD began with the dissolution of Sulfapyridine in anhydrous dimethylformamide (DMF) under alkaline conditions facilitated by potassium carbonate. To this solution, decanoyl chloride was added dropwise, maintaining a controlled temperature of 15-20 °C to prevent side reactions. The reaction mixture was subsequently stirred for four hours at ambient temperature, followed by the addition of excess water to quench the reaction. Vacuum filtration was employed to isolate the crude product, which was extensively washed to remove residual DMF.
The crude SP-PD was purified using silica gel column chromatography with a hexane-ethyl acetate gradient elution system. Thin-layer chromatography (TLC) confirmed the reaction's progress and product identity, visualized under ultraviolet light. High-performance liquid chromatography (HPLC) with a reverse-phase C18 column validated the product's purity. Gradient elution with a mobile phase of water and acetonitrile, both containing 0.1% v/v formic acid, ensured precise quantification of purity.