3-m-chlorobenzyl-4-amino-4,5-dihydro-1H-1,2,4-triazole-5-one | 877315-81-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-m-chlorobenzyl-4-amino-4,5-dihydro-1H-1,2,4-triazole-5-one
• 英文别名: 4-amino-3-[(3-chlorophenyl)methyl]-1H-1,2,4-triazol-5-one
• CAS: 877315-81-6
• 化学式: C₉H₉ClN₄O
• 分子量: 224.65
• InChiKey: VGFOYDCXXHVVOP-UHFFFAOYSA-N

物化性质

• 熔点：
  171-172 °C(Solv: ethanol (64-17-5))
• 密度：
  1.55±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  70.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-m-chlorobenzyl-4-amino-4,5-dihydro-1H-1,2,4-triazole-5-one 、 6-chlorocoumarin-3-carboxylic acid 以 苯 为溶剂， 反应 2.0h， 以86%的产率得到6-chloro-N-[3-(3-chlorobenzyl)-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl]-2-oxo-2H-chromene-3-carboxamide
  参考文献：
  名称：

  包括三唑环在内的一些新香豆素衍生物的合成和抗癌活性及其计算机分子对接研究

  摘要：

  本研究报道了一些含有三唑环的香豆素衍生物的合成、对接研究和抗癌活性研究。筛选新合成的化合物对细胞系 CRL5807（人细支气管肺泡癌）、CRL5826（人鳞状细胞癌）、MDA-MB231（人乳腺癌细胞）、HTB177（人肺癌）、PC- 3（人前列腺腺癌）、PANC-1（人胰腺癌细胞）用作癌细胞，CCD34Lu（正常人肺成纤维细胞）用作健康细胞系。样品的细胞毒性作用通过 MTT（3-（4,5-二甲基-2-噻唑基）-2,5-二苯基-2H-溴化四唑）测定法测定。还进行了计算机研究以探索分子的结合相互作用。

  DOI：

  10.1002/ardp.202000284
• 作为产物：
  描述：

  ethyl m-chlorophenylimidoacetate hydrochloride 在 一水合肼 作用下， 以 乙醇 、 水 为溶剂， 反应 11.0h， 生成 3-m-chlorobenzyl-4-amino-4,5-dihydro-1H-1,2,4-triazole-5-one
  参考文献：
  名称：

  Synthesis of 4-Amino-4,5-dihydro-1H-1,2,4-triazole-5-ones and their Isatin-3-imine Derivatives

  摘要：

  氨基酯盐酸盐 1 已被合成。这些化合物随后被转化为酯乙氧羰酰肼 2，并由此制备出一系列新的 4-氨基-4,5-二氢-1H-1,2,4-三唑-5-酮 3。所有新合成化合物的结构均通过元素分析、红外光谱、1H-NMR 和 13C-NMR 光谱得到证实。

  DOI：

  10.3390/10020376

文献信息

• Synthesis and in vitro antioxidant and antimicrobial activities of novel 3-alkyl(aryl)-4-[3-methoxy-4-(2-furylcarbonyloxy)-benzylidenamino]-4,5-dihydro-1H-1,2,4-triazol-5-ones, and their N-acetyl, N-Mannich base derivatives
  作者：Sevda Manap

  DOI：10.1007/s13738-021-02386-7

  日期：2022.4

  The reactions of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (1) with 3-methoxy-4-(2-furylcarbonyloxy)-benzaldehyde (2) formed 3-alkyl(aryl)-4-[3-methoxy-4-(2-furylcarbonyloxy)-benzylidenamino]-4,5-dihydro-1H-1,2,4-triazol-5-ones (3). Moreover, their five N-acetyl derivatives were synthesized. Besides, 1-(morpholine-4-yl-methyl)-3-alkyl(aryl)-4-[3-methoxy-4-(2-furylcarbonyloxy)-benzylidenamino]-4,5-dihydro-1H-1,2,4-triazol-5-ones (5)/1-(4-methylpiperazin-1-yl-methyl)-3-alkyl(aryl)-4-[3-methoxy-4-(2-furylcarbonyloxy)-benzylidenamino]-4,5-dihydro-1H-1,2,4-triazol-5-ones (6)/1-(piperidine-4-carboxyamide-1-yl-methyl)-3-alkyl(aryl)-4-[3-methoxy-4-(2-furylcarbonyloxy)-benzylidenamino]-4,5-dihydro-1H-1,2,4-triazol-5-ones (7)/N,N′-bis-3-alkyl(aryl)-4-[3-methoxy-4-(2-furylcarbonyloxy)-benzylideneamino]-4,5-dihydro-1H-1,2,4-triazol-5-on-1-yl-methyl}-piperazines (8) were obtained by Mannich reaction between compounds 3 and morpholine/N-methylpiperazine/piperidine-4-carboxyamide/piperazine in the presence of formaldehyde. The newly obtained thirty-four compounds were characterized from IR, 1H NMR, 13C NMR, and MS spectral data. Also, these compounds were evaluated for their in vitro antioxidant activity. Furthermore, in vitro antibacterial activity of the compounds was screened against six bacteria.

  3- 烷基（芳基）-4-氨基-4,5-二氢-1H-1,2,4-三唑-5-酮 (1) 与 3-甲氧基-4-（2-呋喃甲酰氧基）-苯甲醛 (2) 反应生成了 3-烷基（芳基）-4-[3-甲氧基-4-（2-呋喃甲酰氧基）-亚苄基氨基]-4,5-二氢-1H-1,2,4-三唑-5-酮 (3)。此外，还合成了它们的五个 N-乙酰基衍生物。此外，还合成了 1-(吗啉-4-基-甲基)-3-烷基(芳基)-4-[3-甲氧基-4-(2-呋喃甲酰氧基)-亚苄基氨基]-4,5-二氢-1H-1,2,4-三唑-5-酮 (5)/1-(4- 甲基哌嗪-1-基-甲基)-3-烷基(芳基)-4-[3-甲氧基-4-(2-呋喃甲酰氧基)-亚苄基氨基]-4,5-二氢-1H-1,2,4-三唑-5-酮 (6)、5-dihydro-1H-1,2,4-triazol-5-ones (7)/N,N′-bis-3-alkyl(aryl)-4-[3-methoxy-4-(2-furylcarbonyloxy)-benzylideneamino]-4,5-dihydro-1H-1,2,化合物 3 与吗啉/N-甲基哌嗪/哌啶-4-羧酰胺/哌嗪在甲醛存在下发生曼尼希反应，得到了 4,5-二氢-1H-1,2,4-三唑-5-on-1-基-甲基}-哌嗪（8）。根据红外光谱、1H NMR、13C NMR 和 MS 光谱数据对新得到的 34 种化合物进行了表征。此外，还对这些化合物的体外抗氧化活性进行了评估。此外，还筛选了这些化合物对六种细菌的体外抗菌活性。
• Synthesis, design, and assessment of novel morpholine-derived Mannich bases as multifunctional agents for the potential enzyme inhibitory properties including docking study
  作者：Songül Boy、Fikret Türkan、Murat Beytur、Abdülmelik Aras、Onur Akyıldırım、Halide Sedef Karaman、Haydar Yüksek

  DOI：10.1016/j.bioorg.2020.104524

  日期：2021.2

  The synthesized Schiff Bases were reacted with formaldehyde and secondary amine such as 2,6-dimethylmorpholine to afford N-Mannich bases through the Mannich reaction. 3-Substitued-4-(4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (4) were treated with 2,6-dimethylmorpholine in the presence of formaldehyde to synthesize eight new 1-(2,6-dimethylmorpholino-4-yl-methyl)-3-substitued-4-

  合成的席夫碱与甲醛和仲胺如2,6-二甲基吗啉反应，通过曼尼希反应得到N-曼尼希碱。3-取代的-4-（4- hydroxybenzylidenamino）-4,5-二氢-1- ħ -1,2,4-三唑-5-酮（4）在甲醛存在下，以合成用2,6-二甲基吗啉处理八种新的 1-(2,6-dimethylmorpholino-4-yl-methyl)-3-subSTitued-4-(4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones ( 4a-h)。合成的8个新化合物的结构使用IR、1 H NMR、13C NMR和HR-MS光谱方法。合成化合物对乙酰胆碱酯酶 (AChE)、丁酰胆碱酯酶 (BChE) 和谷胱甘肽 S-转移酶 (GST) 的抑制活性测定，AChE 的 Ki 值范围为 25.23-42.19 µM，BChE.8 的 Ki
• Molecular, Electronic, Nonlinear Optical and Spectroscopic Analysis of Heterocyclic 3-Substituted-4-(3-methyl-2-thienylmethyleneamino)-4,5-dihydro-1<i>H</i>-1,2,4-triazol-5-ones: Experiment and DFT Calculations
  作者：Murat Beytur、Ihsan Avinca

  DOI：10.1515/hc-2020-0118

  日期：2021.1.1

  In the present study, 3-p-methoxybenzyl/m-chlorobenzyl/phenyl-4-(3-methyl-2-thienylmethyleneamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones were obtained from the reaction between 3-methylthiophene-2-carbaldehyde and three different 4-amino-(3-p-methoxybenzyl/m-chlorobenzyl/phenyl)-4,5-dihydro-1H-1,2,4-triazole-5-ones. In order to compare experimental and theoretical values, the geometric parameter, electronic, nonlinear optical properties, molecular electrostatic potentials and spectroscopic properties of 3-substituted-4-(3-methyl-2-thienylmethyleneamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones have been simulated. The electronic properties of the newly synthesized compounds were calculated using DFT/B3LYP and DFT/B3PW91 methods revealing parameters such as ionization potential, electron affinity, energy gap, electronegativity, molecular hardness, molecular softness, electrophilic index, nucleophilic index and chemical potential, all obtained from HOMO and LUMO energies, dipole moments and total energies. UV-visible absorption spectra and the stimulation contributions in UV-visible transitions were obtained by using TD-DFT/B3LYP/6-311G(d,p) and TD-DFT/B3PW91/6-311G(d,p) methods in ethanol. The calculated absorption wavelengths, oscillator power and excitation energies were compared with experimental values. In line with DFT, the numbers of molecular vibration were analyzed through the basis set of 6-311G(d,p). The recording of FT-IR frequencies was done for the pertinent compound. The recorded frequencies through DFT/B3LYP and DFT/B3PW91 methods were compared to experimental values, with a result gained closest to the values of B3LYP. Finally, the Gaussian09W program package in DMSO phase, starting from the optimized structure, has been instrumental in calculating the ¹³C-NMR and ¹H-NMR chemical shift values of the GIAO method.

  在本研究中，通过3-p-甲氧基苄/m-氯甲基苄/苯基-4-(3-甲基-2-噻吩甲烯胺基)-4,5-二氢-1H-1,2,4-三唑-5-酮与3-甲基噻吩-2-甲醛和三种不同的4-氨基-(3-p-甲氧基苄/m-氯甲基苄/苯基)-4,5-二氢-1H-1,2,4-三唑-5-酮的反应，获得了3-取代-4-(3-甲基-2-噻吩甲烯胺基)-4,5-二氢-1H-1,2,4-三唑-5-酮。为了比较实验和理论值，对3-取代-4-(3-甲基-2-噻吩甲烯胺基)-4,5-二氢-1H-1,2,4-三唑-5-酮的几何参数、电子、非线性光学性质、分子静电势和光谱性质进行了模拟。新合成化合物的电子性质是使用DFT/B3LYP和DFT/B3PW91方法计算得出的，揭示了离子化势、电子亲和势、能隙、电负性、分子硬度、分子柔软度、亲电指数、亲核指数和化学势等参数，这些参数都是从HOMO和LUMO能量、偶极矩和总能量中获得的。通过在乙醇中使用TD-DFT/B3LYP/6-311G(d,p)和TD-DFT/B3PW91/6-311G(d,p)方法获得了UV-可见吸收光谱和UV-可见跃迁的激发贡献。计算得到的吸收波长、振子强度和激发能与实验值进行了比较。根据DFT，通过6-311G(d,p)基组分析了分子振动的数量。对相关化合物进行了FT-IR频率记录。通过DFT/B3LYP和DFT/B3PW91方法记录的频率与实验值进行了比较，结果最接近B3LYP的值。最后，从优化结构开始，在DMSO相中使用Gaussian09W程序包计算了GIAO方法的¹³C-NMR和¹H-NMR化学位移值。
• Synthesis, Spectroscopic Analysis, and <i>in Vitro/in Silico</i> Biological Studies of Novel Piperidine Derivatives Heterocyclic Schiff‐Mannich Base Compounds
  作者：Songül Boy、Abdülmelik Aras、Fikret Türkan、Onur Akyıldırım、Murat Beytur、Halide Sedef Karaman、Sevda Manap、Haydar Yüksek

  DOI：10.1002/cbdv.202100433

  日期：2021.12

  to afford novel heterocyclic bases. 3-Substitued-4-(4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (T) were treated with 4-piperidinecarboxyamide in the presence of formaldehyde to synthesize eight new 1-(4-piperidinecarboxyamide-1-yl-methyl)-3-substitued-4-(4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (M1-8). The structure characterization of compounds was carried out

  在本研究中，通过处理 4-羟基苯甲醛（B )在乙酸介质中分别使用八种不同的 3-取代-4-氨基-4,5-二氢-1 H -1,2,4-三唑-5-酮 ( T1-8 )。合成的席夫碱( S )与甲醛和仲胺如4-哌啶甲酰胺反应得到新型杂环碱。3-取代-4-(4-羟基苄基氨基)-4,5-dihydro-1 H -1,2,4-triazol-5-ones ( T)在甲醛存在下用4-哌啶甲酰胺处理合成8个新的1-(4-哌啶甲酰胺-1-基-甲基)-3-取代-4-(4-羟基苄基氨基)-4,5-二氢-1H -1,2,4-triazol -5-ones ( M1-8 )。化合物的结构表征使用1 H-NMR、IR、HR-MS 和13 C-NMR 光谱方法进行。计算了新合成的化合物对乙酰胆碱酯酶 (AChE)、丁酰胆碱酯酶 (BChE) 和谷胱甘肽 S-转移酶 (GST) 酶的抑制特性。Ki 值的计算范围为 GST
• Synthesis, Spectroscopic Analysis, Biological Evaluation, and In Silico Studies of Novel Benzenesulfonate-Derived Schiff-Mannich Bases
  作者：Ahmet Harmankaya Ahmet Harmankaya、Nam k K l n Nam k K l n、Murat Beytur Murat Beytur、Yonca Y lmaz Yonca Y lmaz、Sevda Manap and Haydar Y ksek Sevda Manap and Haydar Y ksek

  DOI：10.52568/001280/jcsp/45.04.2023

  日期：——

  In the current study, 3-formyl phenyl benzenesulfonate is created by reacting 3-hydroxybenzaldehyde with benzene sulfonyl chloride, which is aided by triethylamine. Nine unique (Z)-3-[(3-substituted-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl)-iminomethyl] compounds were formed through the reaction of a manufactured 3-formyl phenyl benzenesulfonate chemical with nine 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-one, as detailed in the existing literature. Phenyl benzene sulfonate (S) compounds were purchased. Through the reaction of the Schiff bases that were made a secondary amine, such as morpholine with formaldehyde, heterocyclic Mannich bases of a unique kind were created. Five recently found (Z)-3-[(3-substituted-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl)-iminomethyl] compounds are presented in this work. By reacting phenyl benzene sulfonate (S) with morpholine in the presence of formaldehyde, five new (Z)-3-[(3-substituted-1-(morpholinomethyl)-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl)-iminomethyl] compounds were created. Chemical compounds fall under the category of phenylbenzene sulfonates (M). Utilizing IR, 1H NMR, and 13C NMR spectroscopy, fourteen recently novel compoundsand#39; chemical structures were examined. The ability of the freshly synthesized Schiff and morpholine-derived Mannich bases to obstruct the acetylcholinesterase enzymeand#39;s (AChE) activity was also assessed. The 1,2,4-triazole functional group was modified by adding various groups at the 1 and 3 positions, resulting in a collection of compounds (S1–9 and M1, 2, 4, 5, 7). It was determined whether these synthetic compounds could prevent the human recombinant AR enzyme from working in vitro, and the findings were validated using molecular docking, molecular mechanics, and ADME analyses. To better understand this mechanism, synthetic Schiff and Mannich base derivatives as well as the positive control substance quercetin were tested using molecular docking against the human recombinant AR enzyme in vitro. To assess the drug-like properties of Schiff and Mannich base analogs, a series of absorption, distribution, metabolism, and excretion (ADME) properties were analyzed theoretically.

  在本研究中，3-羟基苯甲醛与苯磺酰氯在三乙胺的帮助下发生反应，生成了 3-甲酰基苯基苯磺酸酯。根据现有文献的详细记载，通过制得的 3-甲酰基苯基苯磺酸盐化学品与九种 3-烷基（芳基）-4-氨基-4,5-二氢-1H-1,2,4-三唑-5-酮反应，形成了九种独特的 (Z)-3-[(3 取代-5-氧代-1,5-二氢-4H-1,2,4-三唑-4-基)-亚氨甲基] 化合物。苯磺酸苯（S）化合物是购买的。通过将制成仲胺（如吗啉）的希夫碱与甲醛反应，产生了一种独特的杂环曼尼希碱。本文介绍了最近发现的五种 (Z)-3-[(3 取代-5-氧代-1,5-二氢-4H-1,2,4-三唑-4-基)-亚氨甲基] 化合物。在甲醛存在下，苯磺酸苯酯（S）与吗啉反应，生成了五种新的（Z）-3-[（3-取代-1-（吗啉甲基）-5-氧代-1,5-二氢-4H-1,2,4-三唑-4-基）-亚氨甲基]化合物。这些化合物属于苯磺酸盐 (M) 类。利用红外光谱、1H NMR 和 13C NMR 光谱，研究了 14 种最新的新型化合物和#39；化学结构。此外，还评估了新合成的席夫碱和吗啉衍生的曼尼希碱阻碍乙酰胆碱酯酶（AChE）活性的能力。通过在 1 位和 3 位添加各种基团对 1,2,4-三唑官能团进行修饰，产生了一系列化合物（S1-9 和 M1、2、4、5、7）。研究人员确定了这些合成化合物是否能阻止人类重组 AR 酶在体外发挥作用，并通过分子对接、分子力学和 ADME 分析验证了研究结果。为了更好地理解这一机制，我们使用分子对接法测试了合成的席夫碱和曼尼希碱衍生物以及阳性对照物质槲皮素对人类重组 AR 酶的体外作用。为了评估希夫碱和曼尼希碱类似物的类药物特性，对其一系列吸收、分布、代谢和排泄（ADME）特性进行了理论分析。