5-(3-甲基苯基)-4H-1,2,4-三唑-3-胺 | 59301-24-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 5-(3-甲基苯基)-4H-1,2,4-三唑-3-胺
• 英文名称: 3-(3-tolyl)-1H-1,2,4-triazol-5-amine
• 英文别名: 5-(3-methylphenyl)-1H-1,2,4-triazol-3-amine
• CAS: 59301-24-5
• 化学式: C₉H₁₀N₄
• mdl: MFCD05182346
• 分子量: 174.205
• InChiKey: DTWHVCOHVMHZSC-UHFFFAOYSA-N

物化性质

• 熔点：
  215 °C (decomp)
• 沸点：
  428.7±38.0 °C(Predicted)
• 密度：
  1.261

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.111
• 拓扑面积：
  67.6
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  5-(3-甲基苯基)-4H-1,2,4-三唑-3-胺 在 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 生成 2-(3-methylphenyl)-5-thioxo-5,6-dihydro-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
  参考文献：
  名称：

  Synthesis andin vitroEvaluation of 1,2,4-Triazolo[1,5-a][1,3,5]triazine Derivatives as Thymidine Phosphorylase Inhibitors

  摘要：

  In our lead finding program, a series of 1,2,4‐triazolo[1,5‐a][1,3,5]triazine derivatives were synthesized, and their in vitro thymidine phosphorylase inhibitory potential was explored. Among the different derivatives, compounds having keto group (C = O) at C7 and thioketo group (C = S) at C5 positions showed varying degrees of TP inhibitory activity comparable with positive control, 7‐deazaxanthine (7‐DX, 2) (IC50 value = 42.63 μm). Enzyme inhibition kinetics study suggested that compound IVn behaved as a mixed‐type inhibitor of the enzyme with respect to thymidine (dThd) as a variable substrate. Compound IVn was also found to inhibit PMA‐induced MMP‐9 expression in MDA‐MB‐231 cells at sublethal concentrations. Computational docking study was performed to illustrate the enzyme inhibition kinetics and to explore the ligand–enzyme interactions.

  DOI：

  10.1111/cbdd.12171
• 作为产物：
  描述：

  间甲苯甲酸酰肼 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 72.0h， 生成 5-(3-甲基苯基)-4H-1,2,4-三唑-3-胺
  参考文献：
  名称：

  A structure–activity relationship study of 1,2,4-triazolo[1,5-a][1,3,5]triazin-5,7-dione and its 5-thioxo analogues on anti-thymidine phosphorylase and associated anti-angiogenic activities

  摘要：

  Thirty-three 1,2,4-triazolo[1,5-a][1,3,5]triazin-5,7-dione and its 5-thioxo analogues were designed and synthesized which contained different substituents at meta- and/or para-positions of 2-phenyl or 2-benzyl ring attached to the fused ring structure. The preliminary pharmacological evaluation demonstrated that the 5-thioxo analogues of 1,2,4-triazolo[1,5-a][1,3,5]triazine exhibited a varying degree of inhibitory activity towards thymidine phosphorylase, comparable or better than reference compound, 7-Deazaxanthine (7-DX, 2) (IC50 value = 42.63 mu M). Moreover, compounds 5q and 6i displayed a mixed-type of inhibitory mechanism in the presence of variable concentrations of thymidine (dThd). In addition, selected compounds were found to have a noticeable inhibitory effect on the expression of angiogenesis markers, including VEGF and MMP-9 in MDA-MB-231 breast cancer cells. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.06.051

文献信息

• A Novel Iron-catalyzed One-pot Synthesis of 3-Amino-1,2,4-triazoles
  作者：Taoufik Rohand、Victor N. Mkpenie、Mohammadine El Haddad、István E. Markó

  DOI：10.1002/jhet.3450

  日期：2019.2

  A novel one‐pot synthesis of 3‐amino‐1,2,4‐triazole developed via iron (III) catalyzed route is reported. The new method is more efficient, simple, and convenient and presents a concise new strategy for the synthesis of 3‐amino‐1,2,4‐triazole derivatives. The iron (III) complex intermediate assisted in the intramolecular bond cyclization owing to its Lewis acidity or oxidizing properties. A series

  据报道，通过铁（III）催化途径开发的一种新型一锅法合成3-氨基1,2,4-三唑。该新方法更加高效，简单和方便，为合成3‐氨基1,2,4‐三唑衍生物提出了一种简洁的新策略。铁（III）配合物中间体由于其路易斯酸度或氧化特性而有助于分子内键的环化。还研究了一系列在对位和/或邻位带有取代的给电子和吸电子基团的芳族腈。取代基的位置影响最终化合物的收率，对位取代的底物收率相对较高。
• 3-Aryl/Heteroaryl-5-amino-1-(3′,4′,5′-trimethoxybenzoyl)-1,2,4-triazoles as antimicrotubule agents. Design, synthesis, antiproliferative activity and inhibition of tubulin polymerization
  作者：Romeo Romagnoli、Filippo Prencipe、Paola Oliva、Stefania Baraldi、Pier Giovanni Baraldi、Andrea Brancale、Salvatore Ferla、Ernest Hamel、Roberta Bortolozzi、Giampietro Viola

  DOI：10.1016/j.bioorg.2018.06.037

  日期：2018.10

  at the 3-position of the 5-amino-1,2,4-triazole system. Most of the twenty-two tested compounds showed moderate to potent antiproliferative activities against a panel of solid tumor and leukemic cell lines, with four (5j, 5k, 5o and 5p) showing strong antiproliferative activity (IC50 < 1 μM) against selected cancer cells. Among them, several molecules preferentially inhibited the proliferation of leukemic

  已知许多天然和合成物质会干扰微管蛋白的动态组装，从而阻止微管的形成。在我们寻找有效的和选择性的抗肿瘤剂中，合成了一系列新的1-（3'，4'，5'-三甲氧基苯甲酰基）-5-氨基-1,2,4-三唑。这些化合物具有不同的杂环，包括噻吩，呋喃或三个同分异构的吡啶，并且它们在5-氨基-1,2,4-三唑体系的3位上具有带电子释放或吸电子取代基的苯环。 。测试的22种化合物中的大多数对一组实体瘤和白血病细胞系均显示出中度至强效的抗增殖活性，其中4种（5j，5k，5o和5p） 对选定的癌细胞显示出强大的抗增殖活性（IC 50 <1μM）。其中，有几种分子优先抑制白血病细胞系的增殖，显示Jurkat和RS4; 11细胞的IC 50值比源自实体瘤的三系（HeLa，HT-29和MCF- 7个单元格）。化合物5k强烈抑制微管蛋白组装，IC 50值为0.66μM，是在CA-4的同时实验中获得的一半（IC 50  =
• Method for reducing a susceptibility to tumor formation induced by 3-deoxyglucosone and precursors thereof
  申请人：Brown R. Truman

  公开号：US20060089316A1

  公开（公告）日：2006-04-27

  Disclosed are methods of using various compounds, which are known to bind to 3-deoxyglucosone (3DG) or precursors thereof, in order to reduce a susceptibility to tumor formation and/or to prevent or delay onset of tumor formation induced by 3DG and its precursors. Also disclosed is the reduction of 3DG levels in high fructose corn syrop so that the high fructose corn syrup is less likely to induce tumor formation.

  公开了使用各种已知与3-脱氧葡萄糖酮（3DG）或其前体结合的化合物的方法，以减少对肿瘤形成的易感性和/或预防或延迟由3DG及其前体诱导的肿瘤形成。还公开了降低高果糖玉米糖浆中3DG水平的方法，以使高果糖玉米糖浆不太可能诱导肿瘤形成。
• Tolstyakov; Pevzner, Russian Journal of Organic Chemistry, 1997, vol. 33, # 12, p. 1803 - 1804
  作者：Tolstyakov、Pevzner

  DOI：——

  日期：——
• Structure–Activity Relationships and Molecular Modeling of 1,2,4-Triazoles as Adenosine Receptor Antagonists
  作者：Jens Carlsson、Dilip K. Tosh、Khai Phan、Zhan-Guo Gao、Kenneth A. Jacobson

  DOI：10.1021/ml300097g

  日期：2012.9.13

  The structure-activity relationship (SAR) for a novel class of 1,2,4-triazole antagonists of the human A(2A) adenosine receptor (hA(2A)AR) was explored. Thirty-three analogs of a ligand that was discovered in a structure-based virtual screen against the hA(2A)AR were tested in hA(1), A(2A), and A(3) radioligand binding assays and in functional assays for the A(2B)AR subtype. As a series of closely related analogs of the initial lead, 1, did not display improved binding affinity or selectivity, molecular docking was used to guide the selection of more distantly related molecules. This resulted in the discovery of 32, a hA(2A)AR antagonist (K-i 200 nM) with high ligand efficiency. In light of the SAR for the 1,2,4-triazole scaffold, we also investigated the binding mode of these compounds based on docking to several A(2A)AR crystal structures.