ethyl 3-(3-(4-methoxyphenyl)thioureido)-1H-indole-2-carboxylate | 686736-60-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: ethyl 3-(3-(4-methoxyphenyl)thioureido)-1H-indole-2-carboxylate
• 英文别名: ethyl 3-[(4-methoxyphenyl)carbamothioylamino]-1H-indole-2-carboxylate
• CAS: 686736-60-7
• 化学式: C₁₉H₁₉N₃O₃S
• 分子量: 369.444
• InChiKey: VYQIEPFRPAVEKS-UHFFFAOYSA-N

物化性质

• 熔点：
  181-182 °C(Solv: ethanol (64-17-5))
• 沸点：
  560.6±60.0 °C(Predicted)
• 密度：
  1.375±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 3-(3-(4-methoxyphenyl)thioureido)-1H-indole-2-carboxylate 在 sodium ethanolate 、 乙酰氯 作用下， 以 乙醇 为溶剂， 反应 12.0h， 生成 3-(4-Methoxyphenyl)-2-sulfanylidene-1,5-dihydropyrimido[5,4-b]indol-4-one
  参考文献：
  名称：

  Identification of Biologically Active Pyrimido[5,4-b]indoles That Prolong NF-κB Activation without Intrinsic Activity

  摘要：

  Most vaccine adjuvants directly stimulate and activate antigen presenting cells but do not sustain immunostimulation of these cells. A high throughput screening (HTS) strategy was designed to identify compounds that would sustain NF-kappa B activation by a stimulus from the Toll-like receptor (TLR)4 ligand, lipopolysaccharide (LPS). Several pilot studies optimized the parameters and conditions for a cell based NF-kappa B reporter assay in human monocytic THP-1 cells. The final assay evaluated prolongation of LPS induced NF-kappa B activation at 12 h. The dynamic range of the assay was confirmed in a pilot screen of 14 631 compounds and subsequently in a main extensive screen with 166 304 compounds. Hit compounds were identified using an enrichment strategy based on unsupervised chemoinformatic clustering, and also by a naive "Top X" approach. A total of 2011 compounds were then rescreened for levels of coactivation with LPS at 5 h and 12 h, which provided kinetic profiles. Of the 407 confirmed hits, compounds that showed correlation of the kinetic profiles with the structural similarities led to identification of four chemotypes: pyrimido[5,4-b]indoles, 4H-chromene-3-carbonitriles, benzo[d][1,3]dioxol-2-ylureas, and tetrahydrothieno[2,3-c]pyridines, which were segregated by 5 h and 12 h kinetic characteristics. Unlike the TLR4 agonistic pyrimidoindoles identified in previous studies, the revealed pyrimidoindoles in the present work did not intrinsically stimulate TLR4 nor induce NF-kappa B but rather prolonged NF-kappa B signaling induced by LPS. A 42-member combinatorial library was synthesized which led to identification of potent N3-alkyl substituted pyrimidoindoles that were not only active in vitro but also enhanced antibody responses in vivo when used as a coadjuvant. The novel HTS strategy led to identification of compounds that are intrinsically quiescent but functionally prolong stimulation by a TLR4 ligand and thereby potentiate vaccine efficacy.

  DOI：

  10.1021/acscombsci.7b00080
• 作为产物：
  描述：

  3-氨基-2-吲哚羧酸乙酯 、 4-甲氧基苯基 异硫氰酸酯 反应 0.5h， 以65%的产率得到ethyl 3-(3-(4-methoxyphenyl)thioureido)-1H-indole-2-carboxylate
  参考文献：
  名称：

  使用Lawesson试剂对4,5-二氢-1,3-噻嗪[5,4-b]吲哚衍生物进行一步封闭。第五个二氢-1,3-噻嗪[b]吲哚异构体

  摘要：

  我们报告了一种合成新环系统的简便方法：4,5-二氢-1,3-噻嗪基[5,4- b ]吲哚。该程序涉及在二氧化硅存在下使用Lawesson试剂，以实现2-苯甲酰基氨基-3-羟甲基吲哚中间体的一步闭环反应，从而提供4,5-二氢-2--2-芳基-1,3-噻嗪基[ 5,4‐ b ]吲哚。通过相应的3-苯基硫脲-2-羧酸酯衍生物，通过化学选择性还原酯基，然后在酸性条件下闭环，可得到2-苯基亚氨基-1,3-噻嗪[5,4- b ]吲哚。红外，1 H-NMR和13阐明了新产品的结构C-NMR光谱，包括2D-HMQC，2D-HMBC和DEPT测量。J.杂环化​​学。（2011）。

  DOI：

  10.1002/jhet.607