Molecular design and biological efficacy: Synthesis of N-(β-oxoethyl)pyrazole derivatives and analysis of their structure-cytotoxicity relationship
Alzhapparova N.A. Panshina S.Y. Ibrayev M.K. Babaev E.V. Shybanov D.E.
March 2026Elsevier B.V.
Journal of the Indian Chemical Society
2026#103Issue 3
Pyrazole (1,2-diazole) derivatives are critical five-membered nitrogen heterocycles widely utilized in medicine, agriculture, and materials science due to their diverse biological activities, including antibacterial, analgesic, and anticancer properties. While N-substituted pyrazoles are pharmacologically significant, the synthesis and toxicological profiles of N-(β-oxoethyl)pyrazoles remain insufficiently explored. In this work, a series of new N-(β-oxoethyl)pyrazole derivatives were prepared in 38–92% yields, while two synthetic routes for the N-acylalkylation of pyrazoles were optimized using aliphatic and aromatic α-bromoketones. The first approach involves the isolation of intermediate pyrazolium salts, while the second utilizes a more efficient one-pot method with K2CO3 for in situ hydrogen bromide neutralization. The structure of the obtained products, including previously undescribed compounds was characterized via IR, NMR, GC-MS, and additionally N-Pivaloyl derivative was characterized by X-ray diffraction (XRD). Mass spectrometry identified characteristic fragmentation patterns ( m/z 28 NH CH+ and m/z 41 NH C CH+) unique to the pyrazole ring cleavage. Cytotoxicity of N-(β-oxoethyl)pyrazoles on Artemia Salina was studied, where it was demonstrated a clear structure-activity relationship (SAR), where that cytotoxicity depends on the type of substituents: donor substituents on the pyrazole ring and pinacolone moieties reduced cytotoxicity, while phenyl substituents and phenacyl groups increased it. Thus, the optimized synthetic routes and the established structure-activity relationship provide a robust basis for the molecular design of pyrazole-containing agents.
Artemia salina , Cytotoxicity , Mass spectrometry , N-(β-oxoethyl)pyrazole , N-acylalkylation , X-ray diffraction , α-bromoketones
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Chemistry Department, Karaganda Buketov University, Karaganda, 100026, Kazakhstan
Chemistry Department, Lomonosov Moscow State University, Moscow, 119899, Russian Federation
Chemistry Department
Chemistry Department
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