New organic salts of the antihypertensive drug hydralazine and their enhanced properties

IF 4.7 2区化学 Q2 CHEMISTRY, PHYSICAL

Journal of Molecular Structure Pub Date : 2025-10-02 DOI:10.1016/j.molstruc.2025.144232

Ming-Hui Qi, Zhe Jin, Minghuang Hong, Bin Zhu, Guo-Bin Ren

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引用次数: 0

Abstract

Hydralazine (HDZ), a vasodilator widely used for the treatment of hypertension, has recently gained renewed attention due to its emerging pharmacological activities, including demethylation and antioxidant effects. Despite its decades-long history, HDZ has been commercialized exclusively in the form of hydralazine hydrochloride, which suffers from limitations such as low permeability and poor bioavailability. In this study, six novel salts of HDZ were synthesized and characterized to explore their potential as superior solid forms with improved physicochemical properties for hypertension treatment or other applications. Comprehensive analyses, including single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), and thermal analysis, were performed to confirm the structures and properties of these salts. Additionally, their equilibrium solubility, intrinsic dissolution rates, and oil-water partition coefficients were evaluated. Among the new salts, HDZ-OA and HDZ-PA demonstrated significantly higher solubility and dissolution rates compared to hydralazine hydrochloride, while HDZ-MA and HDZ-GA exhibited superior lipophilicity. These findings suggest that the newly developed salts offer promising potential as improved solid forms of HDZ.

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降压药肼的新型有机盐类及其增强性能

Hydralazine （HDZ）是一种广泛用于高血压治疗的血管扩张剂，近年来由于其新出现的药理活性，包括去甲基化和抗氧化作用，引起了人们的重新关注。尽管已有数十年的历史，但HDZ仅以盐酸肼嗪的形式商业化，其存在渗透性低和生物利用度差等局限性。在这项研究中，合成并表征了六种新型的HDZ盐，以探索它们作为具有改善的物理化学性质的优越固体形式用于高血压治疗或其他应用的潜力。通过单晶x射线衍射（SCXRD）、粉末x射线衍射（PXRD）和热分析等综合分析，确定了这些盐的结构和性质。此外，还评估了它们的平衡溶解度、固有溶解速率和油水分配系数。新盐中，HDZ-OA和HDZ-PA的溶解度和溶出率明显高于盐酸肼，而HDZ-MA和HDZ-GA的亲脂性优于盐酸肼。这些发现表明，新开发的盐具有改善HDZ固体形式的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Molecular Structure 化学-物理化学

CiteScore

7.10

自引率

15.80%

发文量

2384

审稿时长

45 days

期刊介绍： The Journal of Molecular Structure is dedicated to the publication of full-length articles and review papers, providing important new structural information on all types of chemical species including: • Stable and unstable molecules in all types of environments (vapour, molecular beam, liquid, solution, liquid crystal, solid state, matrix-isolated, surface-absorbed etc.) • Chemical intermediates • Molecules in excited states • Biological molecules • Polymers. The methods used may include any combination of spectroscopic and non-spectroscopic techniques, for example: • Infrared spectroscopy (mid, far, near) • Raman spectroscopy and non-linear Raman methods (CARS, etc.) • Electronic absorption spectroscopy • Optical rotatory dispersion and circular dichroism • Fluorescence and phosphorescence techniques • Electron spectroscopies (PES, XPS), EXAFS, etc. • Microwave spectroscopy • Electron diffraction • NMR and ESR spectroscopies • Mössbauer spectroscopy • X-ray crystallography • Charge Density Analyses • Computational Studies (supplementing experimental methods) We encourage publications combining theoretical and experimental approaches. The structural insights gained by the studies should be correlated with the properties, activity and/ or reactivity of the molecule under investigation and the relevance of this molecule and its implications should be discussed.