Mal Suvadeep, Malik Udita, Mahapatra Monalisa, Mishra Abhishek, Pal Dilipkumar, Paidesetty Sudhir K
Department of Pharmaceutical Chemistry, Siksha 'O' Anusandhan University (Deemed to be University), Bhubaneswar, Odisha, India.
Department of Pharmacy, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur, Chhattisgarh, India.
Drug Dev Res. 2022 Nov;83(7):1469-1504. doi: 10.1002/ddr.21979. Epub 2022 Aug 16.
With different nitrogen-containing heterocyclic moieties, Indazoles earn one of the places among the top investigated molecules in medicinal research. Indazole, an important fused aromatic heterocyclic system containing benzene and pyrazole ring with a chemical formula of C H N , is also called benzopyrazole. Indazoles consist of three tautomeric forms in which 1H-tautomers (indazoles) and 2H-tautomers (isoindazoles) exist in all phases. The tautomerism in indazoles greatly influences synthesis, reactivity, physical and even the biological properties of indazoles. The thermodynamic internal energy calculation of these tautomers points view 1H-indazole as the predominant and stable form over 2H-indazole. The natural source of indazole is limited and exists in alkaloidal nature (i.e., nigellidine, nigeglanine, nigellicine, etc.) found from Nigella plants. Some of the FDA-approved drugs like Axitinib, Entrectinib, Niraparib, Benzydamine, and Granisetron are being used to treat renal cell cancer, non-small cell lung cancer (NSCLC), epithelial ovarian cancer, chronic inflammation, chemotherapy-induced nausea, vomiting, and many more uses. Besides all these advantages regarding its biological activity, the main issue about indazoles is the less abundance in plant sources, and their synthetic derivatives also often face problems with low yield. In this review article, we discuss its chemistry, tautomerism along with their effects, different schematics for the synthesis of indazole derivatives, and their different biological activities.
吲唑含有不同的含氮杂环部分，在药物研究中是研究最多的分子之一。吲唑是一种重要的稠合芳香杂环体系，含有苯环和吡唑环，化学式为C₇H₆N₂，也被称为苯并吡唑。吲唑有三种互变异构形式，其中1H-互变异构体（吲唑）和2H-互变异构体（异吲唑）在所有相中都存在。吲唑中的互变异构极大地影响了吲唑的合成、反应性、物理性质甚至生物学性质。这些互变异构体的热力学内能计算表明，1H-吲唑比2H-吲唑更占优势且更稳定。吲唑的天然来源有限，存在于从黑种草属植物中发现的生物碱性质中（即黑种草定碱、黑种草胺、黑种草碱等）。一些已获美国食品药品监督管理局（FDA）批准的药物，如阿昔替尼、恩曲替尼、尼拉帕利、苄达明和格拉司琼，正被用于治疗肾细胞癌、非小细胞肺癌（NSCLC）、上皮性卵巢癌、慢性炎症、化疗引起的恶心、呕吐等多种病症。除了其生物学活性方面的所有这些优点外，吲唑的主要问题是植物来源中含量较少，其合成衍生物也常常面临产率低的问题。在这篇综述文章中，我们讨论了吲唑的化学、互变异构及其影响、吲唑衍生物合成的不同示意图以及它们不同的生物学活性。
