Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran | Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
Mini Rev Med Chem. 2021;21(19):2874-2928. doi: 10.2174/1389557521666210315163045.
1, 2, 4-Triazine derivatives have received much attention due to their multifunctional nature, especially in diverse pharmacological properties as well as a key fragment in many drug candidates. Introduction of a vicinal 5, 6-diaryl/heteroaryl moiety on the 1, 2, 4-triazine ring has attracted plentiful attention in the field of medicinal chemistry. 5, 6-Diaryl/heteroaryl-3-substituted-1, 2, 4- triazine is a prominent scaffold in many drug candidates, which has shown a wide range of pharmacological activities such as anti-diabetic, antifungal, anti-inflammatory, anticancer, anti-HIV, neuroprotective, anticonvulsant, anti-Alzheimer, anti-Parkinson, and antioxidant. In this review, we have discussed synthesis, various pharmacological activities of 5, 6-diaryl/heteroaryl-3-substituted-1, 2, 4- triazines, their structure-activity relationship (SAR), pharmacophoric elements, and their mechanism of action reported in the published articles during 2000-2019. Evaluation of compounds by PAINS filtering tool was accomplished and showed that this versatile structure could be considered as a privileged structure. Compilation of the biological data confirmed that position 3 of the 1,2,4-triazine is a key location to determine the affinity and selectivity of the 5,6-diaryl/heteroaryl-3-substituted-1, 2, 4- triazines towards different biologic targets. Specific geometrical and thermodynamic characters of this motif have prompted it as a frequent hitter.
1, 2, 4-三嗪衍生物因其多功能性而备受关注，尤其是在多样化的药理学特性以及许多药物候选物中的关键片段方面。在 1, 2, 4-三嗪环上引入相邻的 5, 6-二芳基/杂芳基部分引起了药物化学领域的广泛关注。5, 6-二芳基/杂芳基-3-取代-1, 2, 4-三嗪是许多药物候选物中的重要骨架，它表现出广泛的药理学活性，如抗糖尿病、抗真菌、抗炎、抗癌、抗 HIV、神经保护、抗惊厥、抗阿尔茨海默病、抗帕金森病和抗氧化。在这篇综述中，我们讨论了 5, 6-二芳基/杂芳基-3-取代-1, 2, 4-三嗪的合成、各种药理学活性、构效关系（SAR）、药效团元素及其在 2000-2019 年发表的文献中报道的作用机制。通过 PAINS 过滤工具对化合物进行了评估，结果表明这种多功能结构可以被认为是一种特权结构。生物数据的汇编证实，1,2,4-三嗪的 3 位是确定 5,6-二芳基/杂芳基-3-取代-1, 2, 4-三嗪对不同生物靶标亲和力和选择性的关键位置。该结构基序的特定几何和热力学特性使其成为一种常见的命中目标。
