Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, 500 03, Hradec Králové, Czech Republic.
Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, 500 03, Hradec Králové, Czech Republic.
Eur J Med Chem. 2024 Dec 5;279:116835. doi: 10.1016/j.ejmech.2024.116835. Epub 2024 Sep 5.
This review comprehensively summarizes recent advances in the field of hydrazinecarboxamide (semicarbazide) derivatives, highlighting their significant therapeutic potential and a broad spectrum of biological activities. As a promising and privileged scaffold in medicinal chemistry, hydrazinecarboxamides have emerged as a versatile class of compounds with significant bioactive properties. Based on their substitutions, their structural diversity permits extensive chemical modifications to enhance their interactions with various biological targets to combat multiple disorders. Notable, this group of compounds has shown significant efficacy against numerous cancer cell lines through diverse mechanisms of action and potent inhibition of enzymes, including cholinesterases, carbonic anhydrases, cyclooxygenases, lipoxygenases, etc. Beyond these, they have also been investigated for their anticonvulsive, analgesic/anti-inflammatory, and antioxidant properties, with detailed structure-activity relationships. For many applications, the hybridization of hydrazinecarboxamides with other bioactive scaffolds, such as primaquine, is of particular interest and offers advantages. Despite their promises, challenges such as suboptimal physicochemical properties and selectivity issues of certain derivatives require further effort. The review aims to inspire future innovation in the design and development of new potential hydrazinecarboxamide-based drugs, addressing existing challenges and expanding their therapeutic applications.
这篇综述全面总结了肼基甲酰胺(氨基脲)衍生物领域的最新进展,强调了它们具有重要的治疗潜力和广泛的生物活性。作为药物化学中一种有前途的和受优待的支架,肼基甲酰胺已经成为一类具有显著生物活性的多功能化合物。基于其取代基,其结构多样性允许进行广泛的化学修饰,以增强与各种生物靶标的相互作用,从而对抗多种疾病。值得注意的是,该类化合物通过多种作用机制和对酶(包括胆碱酯酶、碳酸酐酶、环氧化酶、脂氧合酶等)的有效抑制,对许多癌细胞系表现出显著的疗效。除此之外,它们还因其抗惊厥、镇痛/抗炎和抗氧化特性而受到研究,详细的构效关系也有报道。对于许多应用,肼基甲酰胺与其他生物活性支架(如伯氨喹)的杂交尤其受到关注,并具有优势。尽管具有这些潜力,但某些衍生物的物理化学性质不佳和选择性问题等挑战仍需要进一步努力。该综述旨在为设计和开发新的潜在基于肼基甲酰胺的药物提供启示,以应对现有挑战并扩大其治疗应用。