2-(tert-butoxycarbonylaminomethyl)-1,3-thiazole-4-carbothioamide | 182120-83-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(tert-butoxycarbonylaminomethyl)-1,3-thiazole-4-carbothioamide
• 英文别名: tert-butyl ((4-carbamothioylthiazol-2-yl)methyl)carbamate；2-(tert-butoxycarbonylaminomethyl)-thiazole-4-carbothioamide；Tert-butyl N-[(4-carbamothioyl-1,3-thiazol-2-YL)methyl]carbamate；tert-butyl N-[(4-carbamothioyl-1,3-thiazol-2-yl)methyl]carbamate
• CAS: 182120-83-8
• 化学式: C₁₀H₁₅N₃O₂S₂
• 分子量: 273.38
• InChiKey: AQQCPIJDNPUTHG-UHFFFAOYSA-N

物化性质

• 熔点：
  146-147 °C(Solv: hexane (110-54-3); ethyl acetate (141-78-6))
• 密度：
  1.302±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  138
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 储存条件：
  存储温度应保持在2-8°C，并请避免光照。

反应信息

• 作为反应物：
  描述：

  2-(tert-butoxycarbonylaminomethyl)-1,3-thiazole-4-carbothioamide 在 盐酸 作用下， 以 二氯甲烷 为溶剂， 生成 2-Aminomethyl-thiazole-4-thiocarboxamide
  参考文献：
  名称：

  Thrombin inhibitors

  摘要：

  新型五元杂环胺基化物，其制备和用作胰蛋白酶样丝氨酸蛋白酶的竞争性抑制剂，特别是血栓素和激肽原酶如激肽原酶的抑制剂。含有这些化合物作为活性成分的药物组合物，以及将这些化合物用作血栓素抑制剂、抗凝剂和抗炎药剂。

  公开号：

  US06740647B1
• 作为产物：
  描述：

  2-((叔丁氧羰基氨基)甲基)噻唑-4-甲酸乙酯 在 劳森试剂 、 ammonium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 32.0h， 生成 2-(tert-butoxycarbonylaminomethyl)-1,3-thiazole-4-carbothioamide
  参考文献：
  名称：

  候选前大肠杆菌素的收敛和模块化合成。Precolibactin A 的结构修正

  摘要：

  大肠杆菌素是由某些共生和肠外致病性大肠杆菌菌株产生的混合聚酮化合物-非核糖体肽天然产物。代谢物由 clb 基因簇编码，称为前体药物。clb(+) 大肠杆菌在体外和体内诱导哺乳动物细胞 DNA 双链断裂，并且在 55-67% 的结肠直肠癌患者中发现，表明成熟的大肠杆菌素可以引发肿瘤发生。然而，阐明它们的结构一直是一项艰巨的任务，因为从细菌培养物中获得的代谢物数量极少 (μg/L)，并且被认为是不稳定的。在此，我们描述了一种灵活且收敛的合成路线来制备先进的前大肠杆菌素和衍生物。合成通过两个复杂前体（例如，28 + 17 → 29a，90%），然后是碱诱导的双脱水级联反应，形成两个目标环（例如，29a → 30a，79%）。该序列提供了超过发酵获得的数量的先进候选前大肠杆菌素的数量，并且预计可以很容易地进行缩放。这些研究指导了预测代谢物 precolibactin A（从 5a 或 5b 到 7）的结构修订，并证实了分离的代谢物

  DOI：

  10.1021/jacs.6b02276

文献信息

• [EN] DNA ALKYLATION AND CROSS-LINKING AGENTS AS COMPOUNDS AND PAYLOADS FOR TARGETED THERAPIES<br/>[FR] ALKYLATION D'ADN ET AGENTS DE RÉTICULATION COMME COMPOSÉS ET CHARGES UTILES POUR THÉRAPIES CIBLÉES
  申请人：UNIV YALE

  公开号：WO2017132459A1

  公开（公告）日：2017-08-03

  The present invention is directed to compounds related to precolibactin, pharmaceutical compositions based upon these compounds and methods of synthesis which are employed to provide intermediates and final compounds, which are principally alkylating agents and anticancer compounds. The chemical synthetic approach disclosed facilitates the synthesis of numerous precolibactin analogs which can be used in the treatment of cancer.

  本发明涉及与precolibactin相关的化合物，基于这些化合物的药物组合物以及用于提供中间体和最终化合物的合成方法，这些化合物主要是烷基化剂和抗癌化合物。所披露的化学合成方法有助于合成多种precolibactin类似物，可用于癌症治疗。
• Synthesis and Biological Characterization of the Histone Deacetylase Inhibitor Largazole and C7- Modified Analogues
  作者：José A. Souto、Esther Vaz、Ilaria Lepore、Ann-Christin Pöppler、Gianluigi Franci、Rosana Álvarez、Lucia Altucci、Ángel R. de Lera

  DOI：10.1021/jm100244y

  日期：2010.6.24

  Largazole 4a and analogues with modifications at the C7 position, as well as 2,4'-bithiazole 5a, have been synthesized using an acyclic cross-metathesis of the corresponding depsipeptide structures assembled by N-C6(O) or C15(O)-N lactam formation. Similar to the parent system 4a, the series of largazole depsipeptides 4b-d, but not 2,4'-bithiazole 5a, showed a marked inhibition of recombinant HDAC1 and selectivity over HDAC4, as well as strong pro-apoptotic effects on the NB4 leukemia cell line, but they failed to induce differentiation to mature granulocytes. Functional assays of the analogues correlated with the in vitro activities, as shown by increased H3 and a-tubulin acetylation levels and p21(WAF1/C1P1) up-regulation in NB4 cells. The activity of the natural product HDACi largazole 4a is not significantly altered by the presence of groups of different size (H, Et, Ph) at C7 on the dihydrothiazole ring.
• RITA Mimics: Synthesis and Mechanistic Evaluation of Asymmetric Linked Trithiazoles
  作者：Adrian L. Pietkiewicz、Yuqi Zhang、Marwa N. Rahimi、Michael Stramandinoli、Matthew Teusner、Shelli R. McAlpine

  DOI：10.1021/acsmedchemlett.6b00488

  日期：2017.4.13

  The established cytotoxic agent RITA contains a thiophene-furan-thiophene backbone and two terminal alcohol groups. Herein we investigate the effect of using thiazoles as the backbone in RITA-like molecules and modifying the terminal groups of these trithiazoles, thereby generating 41 unique structures. Incorporating side chains with varied steric bulk allowed us to investigate how size and a stereocenter impacted biological activity. Subjecting compounds to growth inhibition assays on HCT-116 cells showed that the most potent compounds 7d, 7e, and 7h had GI₅₀ values of 4.4, 4.4, and 3.4 μM, respectively, versus RITA (GI₅₀ of 800 nM). Analysis of these compounds in apoptosis assays proved that 7d, 7e, and 7h were as effective as RITA at inducing apoptosis. Evaluating the impact of 7h on proteins targeted by RITA (p53, c-Myc, and Mcl-1) indicated that it acts via a different mechanism of action to that of RITA. RITA suppressed Mcl-1 protein via p53, whereas compound 7h suppressed Mcl-1 expression via an alternative mechanism independent of p53.
• Videnov, Georgi; Kaiser, Dietmar; Kempter, Christoph, Angewandte Chemie, 1996, vol. 108, # 13/14, p. 1604 - 1607
  作者：Videnov, Georgi、Kaiser, Dietmar、Kempter, Christoph、Jung, Guenther

  DOI：——

  日期：——
• DNA ALKYLATION AND CROSS-LINKING AGENTS AS COMPOUNDS AND PAYLOADS FOR TARGETED THERAPIES
  申请人：YALE UNIVERSITY

  公开号：US20190031650A1

  公开（公告）日：2019-01-31

  The present invention is directed to compounds related to precolibactin pharmaceutical compositions based upon these compounds and methods of synthesis which are employed to provide intermediates and final compounds, which are principally alkylating agents and anticancer compounds. The chemical synthetic approach disclosed facilitates the synthesis of numerous precolibactin analogs which can be used in the treatment of cancer.