sodium 4-methyl-1-piperazinecarbodithioate | 5712-49-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: sodium 4-methyl-1-piperazinecarbodithioate
• 英文别名: sodium 4-methylpiperazine-1-carbodithioate；1-Piperazinecarbodithioic acid, 4-methyl-, sodium salt；sodium;4-methylpiperazine-1-carbodithioate
• CAS: 5712-49-2
• 化学式: C₆H₁₁N₂S₂*Na
• 分子量: 198.289
• InChiKey: JPKVEDOCKBMPHK-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -2.93
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  39.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  sodium 4-methyl-1-piperazinecarbodithioate 在 碘 、 potassium iodide 作用下， 以 水 为溶剂， 反应 3.0h， 生成 双(4-甲基-1-1-哌嗪基硫代甲酰基)二硫
  参考文献：
  名称：

  Exploring the Structural Requirements for Inhibition of the Ubiquitin E3 Ligase Breast Cancer Associated Protein 2 (BCA2) as a Treatment for Breast Cancer

  摘要：

  The zinc-ejecting aldehyde dehydrogenase (A LDH) inhibitory drug disulfiram (DS F) was found to be a breast cancer-associated protein 2 (BCA2) inhibitor with potent antitumor activity. We herein describe our work in the synthesis and evaluation of new series of zinc-affinic molecules to explore the structural requirements for selective BCA2-inhibitory antitumor activity. An N(C=S)S-S motif was found to be required, based on selective activity in BCA2-expressing breast cancer cell lines and against recombinant BCA2 protein. Notably, the DSF analogs (3a and 3c) and dithio(peroxo)thioate compounds (5d and 5f) were found to have potent activity (submicromolar IC(50)) in BCA2 positive MCF-7 and T47D cells but were inactive (IC(50)> 10 mu M) in BCA2 negative M DA-MB-231 breast cancer cells and the normal breast epithelial cell line MCF10A. Testing in the isogenic BCA2 +ve M DA-MB-231/ER cell line restored antitumor activity for compounds that were inactive in the BCA2 -ve MDA-MB-231 cell line. In contrast, structurally related dithiocarbamates and benzisothiazolones (lacking the disulfide bond) were all inactive. Compounds 5d and 5f were additionally found to lack ALDH-inhibitory activity, suggestive of selective E3 ligase-inhibitory activity and worthy of further development.

  DOI：

  10.1021/jm901757t
• 作为产物：
  描述：

  N-甲基哌嗪 、 二硫化碳 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 sodium 4-methyl-1-piperazinecarbodithioate
  参考文献：
  名称：

  带有二硫代氨基甲酸酯的新磺酰胺衍生物的合成，表征和碳酸酐酶I和II的抑制性评估。

  摘要：

  在这项研究中，合成了新型的二硫代氨基甲酸酯-磺酰胺衍生物（3a-3k）以研究其对纯化的人碳酸酐酶（hCA）Ⅰ和Ⅱ的抑制活性。计算化合物的IC50和Ki值，以比较它们对hCA I和II同工酶的抑制曲线。乙酰唑胺用作酶抑制试验中的标准抑制剂。化合物3a，3e，3g，3h，3j和3k显示出对hCA I和II的显着抑制作用。在这些化合物中，发现化合物3h是针对hCA I和II酶的最具活性的衍生物，Ki值分别为0.032±0.001μM和0.013±0.0005μM。观察到化合物3a，3e，3g，3h，3j和3k对NIH / 3T3（小鼠胚胎成纤维细胞系）的细胞毒性，发现该化合物无细胞毒性。此外，进行了分子对接研究，以研究化合物3h与hCA I和II酶之间的相互作用类型。这项研究的结果是，鉴定了一种新型且有效的具有良好活性潜能的CA抑制剂。

  DOI：

  10.1016/j.ejmech.2020.112392

文献信息

• Design, synthesis and pharmacological analysis of 5-[4′-(substituted-methyl)[1,1′-biphenyl]-2-yl]-1H-tetrazoles
  作者：Atulkumar Kamble、Ravindra Kamble、Suneel Dodamani、Sunil Jalalpure、Vijaykumar Rasal、Mahadev Kumbar、Shrinivas Joshi、Sheshagiri Dixit

  DOI：10.1007/s12272-017-0887-0

  日期：2017.4

  In the present paper 5-[4′-(4-[(4-aryloxy)methyl]-1H-1,2,3-triazol-1-yl}methyl)[1,1′-biphenyl]-2-yl]-1H-tetrazoles (5a–g) and [2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-yl]methyl-substituted-1-carbodithioates (11h–q) have been designed and synthesized. These compounds were subjected to docking (against AT1 receptor protein enzyme in complex with Lisinopril), in vitro angiotensin converting enzyme inhibition

  在本文中 5-[4'-(4-[(4-芳氧基)甲基]-1H-1,2,3-三唑-1-基}甲基)[1,1'-联苯]-2-基]-1H-四唑 (5a-g) 和 [2'-(1H-四唑-5-基)[1,1'-联苯]-4-基]甲基-取代的-1-碳二硫代酸酯 (11h-q)已经设计和合成。这些化合物经过对接（针对与赖诺普利复合的 AT1 受体蛋白酶）、体外血管紧张素转化酶抑制、抗增殖、抗炎筛选（通过卵白蛋白变性抑制和红细胞膜稳定试验），最后抗- 真菌活性分析。一些化合物已显示出显着的药理特性。
• Synthesis of <i>S</i>-(2-Thioxo-1,3-dithiolan-4-yl)methyl Dialkylcarbamothioate and <i>S</i>-Thiiran-2-ylmethyl Dialkylcarbamothioate via Intermolecular O−S Rearrangement in Water^,
  作者：Nand Lal、Lalit Kumar、Amit Sarswat、Santosh Jangir、Vishnu Lal Sharma

  DOI：10.1021/ol2005825

  日期：2011.5.6

  3-dithiolan-4-yl)methyl dialkylcarbamothioates (3) and S-thiiran-2-ylmethyl dialkylcarbamothioate (5) has been reported by the reaction of 5-(chloromethyl)-1,3-oxathiolane-2-thione (1) with sodium dialkylcarbamodithioate (2) and dialkylamine (4), respectively, through intermolecular O−S rearrangement in water. A plausible mechanism of formation of the title compounds has also been proposed.

  据报道，通过5-（氯甲基）的反应可以轻松合成S-（2-硫代-1,3-二硫杂环戊-4-基）甲基二烷基氨基甲酸酯（3）和S-噻喃-2-基甲基二烷基氨基甲酸酯（5）。 -1,3-氧杂硫杂环戊烷-2-硫酮（1）与二烷基氨基甲磺酸二钠（2）和二烷基胺（4）通过在水中的分子间OS重排。还提出了标题化合物形成的合理机理。
• Synthesis, anticandidal activity, and cytotoxicity of some thiazole derivatives with dithiocarbamate side chains
  作者：Leyla YURTTAŞ、Yusuf ÖZKAY、Fatih DEMİRCİ、Gamze GÖGER、Şafak ULUSOYLAR YILDIRIM、Usama ABU MOHSEN、Ömer ÖZTÜRK、Zafer Asım KAPLANCIKLI

  DOI：10.3906/kim-1312-62

  日期：——

  Some thiazole derivatives bearing dithiocarbamic acid esters were synthesized in order to investigate their anticandidal activity and cytotoxicity. The structures of the obtained final compounds (6a--j) were confirmed by spectral data (IR, ^1H NMR, ^13}C NMR, and MS) and elemental analysis. The anticandidal activity of the compounds was determined (6a--j) using the microbroth dilution method and their cytotoxicity was evaluated according to the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay against normal cells. Contrary to expectations, weak antifungal activity was observed with IC_50} values ranging between 30 and 403 \mu g/mL.

  为了研究一些噻唑衍生物的抗真菌活性和细胞毒性，合成了一系列含有二硫代氨基甲酸酯的噻唑类化合物。通过光谱数据（IR、¹H NMR、¹³C NMR 和 MS）和元素分析确认了所得最终化合物（6a-j）的结构。采用微量肉汤稀释法测定这些化合物的抗真菌活性（6a-j），并通过MTT（3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑盐溴）法测定其对正常细胞的细胞毒性。与预期相反，观察到的抗真菌活性较弱，IC₅₀值在30至403 µg/mL之间。
• Role of disulfide linkage in action of bis(dialkylaminethiocarbonyl)disulfides as potent double-Edged microbicidal spermicide: Design, synthesis and biology
  作者：Nand Lal、Santosh Jangir、Veenu Bala、Dhanaraju Mandalapu、Amit Sarswat、Lalit Kumar、Ashish Jain、Lokesh Kumar、Bhavana Kushwaha、Atindra K. Pandey、Shagun Krishna、Tara Rawat、Praveen K. Shukla、Jagdamba P. Maikhuri、Mohammad I. Siddiqi、Gopal Gupta、Vishnu L. Sharma

  DOI：10.1016/j.ejmech.2016.03.012

  日期：2016.6

  generally treated by Metronidazole and Fluconazole respectively. Poor vaginal efficacy, drug-resistance and non-spermicidal nature limit their use as topical microbicidal contraceptives. Bis(dialkylaminethiocarbonyl)disulfides (4–38) were designed as dually active, non-surfactant molecules capable of eliminating Trichomonas vaginalis and Candida strains as well as irreversibly immobilizing 100% human sperm

  滴虫病和念珠菌病是最常见的致病性生殖道感染，通常分别用甲硝唑和氟康唑治疗。阴道功效差，耐药性和非杀精性限制了它们作为局部杀微生物避孕药的使用。双（二烷基胺硫代羰基）二硫化物（4 – 38）被设计为具有双重活性的非表面活性剂分子，能够消除阴道毛滴虫和念珠菌菌株，并且能够以不可细胞毒性的剂量立即不可逆地固定100％人类精子，对人类宫颈上皮细胞和体外阴道菌群。化合物12，16，17它们的活性是非氧化酚9，OTC阴道杀精子剂的50倍，并且化合物12和17在兔模型中显示出显着的体内活性。最有前途的化合物17由于具有更高的活性和安全性以及显着的体内滴虫杀菌活性，已显示出有望进一步发展为双刃阴道杀微生物剂。二硫化物基团的作用是由于化学修饰过程中杀精子活性的丧失而确立的（39 – 56）。这些二硫化物可能靶向存在于人精子和滴虫的细胞膜上的巯基，如游离巯基的荧光标记所示。
• Novel imidazole derivatives as antifungal agents: Synthesis, biological evaluation, ADME prediction and molecular docking studies
  作者：Firuze Diyar Altındağ、Begüm Nurpelin Sağlık、Ulviye Acar Çevik、İlhan Işıkdağ、Yusuf Özkay、Hülya Karaca Gençer

  DOI：10.1080/10426507.2019.1565761

  日期：2019.9.2

  connection between activities and physicochemical properties of the target compounds was determined. Most of the final compounds exhibited significant activity against Candida albicans and Candida krusei with MIC50 value 12.5 μg/mL. The results of in vitro anti-Candida activity, a docking study and ADME prediction revealed that the newly synthesized compounds have potential anti-Candida activity and evidenced

  摘要 设计并合成了一系列 2-(取代二硫代氨基甲酰基)-N-[4-((1H-咪唑-1-基)甲基)苯基]乙酰胺衍生物以对抗耐药性真菌感染的发病率不断增加。所有合成的化合物均通过 IR、1H-NMR、13C-NMR 和 HRMS 光谱和元素分析进行​​表征。针对四种不同的真菌菌株进行了抗真菌活性测试。进行分子对接研究以研究对真菌羊毛甾醇 14α-脱甲基酶（一种细胞色素 P450 依赖性酶）的作用模式。进行了 ADME 研究并确定了目标化合物的活性和理化性质之间的联系。大多数最终化合物对白色念珠菌和克柔念珠菌表现出显着的活性，MIC50 值为 12.5 μg/mL。体外抗念珠菌活性、对接研究和 ADME 预测的结果表明，新合成的化合物具有潜在的抗念珠菌活性，并证明活性最强的衍生物 5b（2-吡咯烷硫代羰基硫基-N-[4-（（1H-咪唑-1-基)甲基)苯基]乙酰胺)，可以进一步优化作为先导化合物。图形概要