(R)-tert-butyl 1-(4-carbamoylthiazol-2-yl)-2-phenylethylcarbamate | 1315334-25-8

• 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: (R)-tert-butyl 1-(4-carbamoylthiazol-2-yl)-2-phenylethylcarbamate
• 英文别名: tert-butyl N-[(1R)-1-(4-carbamoyl-1,3-thiazol-2-yl)-2-phenylethyl]carbamate
• CAS: 1315334-25-8
• 化学式: C₁₇H₂₁N₃O₃S
• 分子量: 347.438
• InChiKey: ZZARSMKLASQEIO-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  123
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-tert-butyl 1-(4-carbamoylthiazol-2-yl)-2-phenylethylcarbamate 在 劳森试剂 、 ammonium hydroxide 、 potassium hydrogencarbonate 作用下， 以 甲醇 、 乙二醇二甲醚 、 苯 为溶剂， 反应 0.25h， 生成
  参考文献：
  名称：

  RITA Mimics: Synthesis and Mechanistic Evaluation of Asymmetric Linked Trithiazoles

  摘要：

  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.

  DOI：

  10.1021/acsmedchemlett.6b00488
• 作为产物：
  描述：

  Boc-D-苯丙氨酸 在 劳森试剂 、 2,6-二甲基吡啶 、 氨 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 potassium hydrogencarbonate 、 N,N-二异丙基乙胺 、 三氟乙酸酐 作用下， 以 甲醇 、 乙二醇二甲醚 、 二氯甲烷 、 水 为溶剂， 反应 26.33h， 生成 (R)-tert-butyl 1-(4-carbamoylthiazol-2-yl)-2-phenylethylcarbamate
  参考文献：
  名称：

  拉加唑类似物的噻唑-噻唑啉片段的合成

  摘要：

  海洋天然产物largazole（一种有效的组蛋白脱乙酰基酶1抑制剂）的噻唑-噻唑啉片段已通过五个步骤合成。该方法可以快速获得噻唑-4-腈，噻唑-4-氨基甲酸酯，噻唑-恶唑啉和其他噻唑-噻唑啉衍生物，它们是许多具有重要生物学特性的天然产物的总合成中的重要中间体。

  DOI：

  10.1021/jo201675r

文献信息

• Synthesis of the Thiazole–Thiazoline Fragment of Largazole Analogues
  作者：Frederik Diness、Daniel S. Nielsen、David P. Fairlie

  DOI：10.1021/jo201675r

  日期：2011.12.2

  fragment of the marine natural product largazole, a potent histone deacetylase 1 inhibitor, has been synthesized in five steps. The methodology provides rapid access to thiazole-4-carbonitrile, thiazole-4-carbimidate, thiazole–oxazoline, and other thiazole–thiazoline derivatives that are important intermediates in the total synthesis of many natural products with important biological properties.

  海洋天然产物largazole（一种有效的组蛋白脱乙酰基酶1抑制剂）的噻唑-噻唑啉片段已通过五个步骤合成。该方法可以快速获得噻唑-4-腈，噻唑-4-氨基甲酸酯，噻唑-恶唑啉和其他噻唑-噻唑啉衍生物，它们是许多具有重要生物学特性的天然产物的总合成中的重要中间体。
• Total synthesis of largazole and analogues: HDAC inhibition, antiproliferative activity and metabolic stability
  作者：Hanae Benelkebir、Sabrina Marie、Annette L. Hayden、Jason Lyle、Paul M. Loadman、Simon J. Crabb、Graham Packham、A. Ganesan

  DOI：10.1016/j.bmc.2011.02.024

  日期：2011.6

  The total synthesis of largazole and four analogues is reported. All analogues were nanomolar HDAC inhibitors. The antiproliferative activity is driven by lipophilicity and cell permeability. In murine liver homogenates, largazole is rapidly metabolized (half-life <= 5 min) to the thiol which has a half-life of 51 min. (C) 2011 Elsevier Ltd. All rights reserved.
• 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.