8-(2-aminoethyl)-6-methyl-4,4-dioxo-1H-pyrrolo[3,2-g][1,4]benzothiazine-5,9-dione;hydrochloride | 1520083-80-0

• 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: 8-(2-aminoethyl)-6-methyl-4,4-dioxo-1H-pyrrolo[3,2-g][1,4]benzothiazine-5,9-dione;hydrochloride
• CAS: 1520083-80-0
• 化学式: C₁₃H₁₃N₃O₄S*ClH
• 分子量: 343.791
• InChiKey: IUDMMTZHCOPRCG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.03
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  120
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-(4-(benzyloxy)-1H-indol-3-yl)ethanamine 在 盐酸 、 sodium dihydrogenphosphate 、 potassium nitrososulfonate 、 palladium 10% on activated carbon 、 水 、 氢气 、 氧气 、 三乙胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 二甲基亚砜 、 乙腈 为溶剂， 反应 108.0h， 生成 8-(2-aminoethyl)-6-methyl-4,4-dioxo-1H-pyrrolo[3,2-g][1,4]benzothiazine-5,9-dione;hydrochloride
  参考文献：
  名称：

  Total Synthesis of Thiaplakortone A: Derivatives as Metabolically Stable Leads for the Treatment of Malaria

  摘要：

  Thiaplakortone A (3a), an antimalarial natural product, was prepared by an operationally simple and scalable synthesis. In our efforts to deliver a lead compound with improved potency, metabolic stability, and selectivity, the synthesis was diverted to access a series of analogues. Compounds, 3a-d showed nanomolar activity against the chloroquine-sensitive (3D7) Plasmodium falciparum line and were more active against the chloroquine- and mefloquine-resistant (Dd2) P. falciparum line. All compounds are "Rule-of-5" compliant, and we show that metabolic stability can be enhanced via modification at either the primary or pyrrole nitrogen. These promising results lay the foundation for the development of this structurally unprecedented natural product.

  DOI：

  10.1021/ml400447v

文献信息

• Total Synthesis of Thiaplakortone A: Derivatives as Metabolically Stable Leads for the Treatment of Malaria
  作者：Rebecca H. Pouwer、Sophie M. Deydier、Phuc Van Le、Brett D. Schwartz、Nicole C. Franken、Rohan A. Davis、Mark J. Coster、Susan A. Charman、Michael D. Edstein、Tina S. Skinner-Adams、Katherine T. Andrews、Ian D. Jenkins、Ronald J. Quinn

  DOI：10.1021/ml400447v

  日期：2014.2.13

  Thiaplakortone A (3a), an antimalarial natural product, was prepared by an operationally simple and scalable synthesis. In our efforts to deliver a lead compound with improved potency, metabolic stability, and selectivity, the synthesis was diverted to access a series of analogues. Compounds, 3a-d showed nanomolar activity against the chloroquine-sensitive (3D7) Plasmodium falciparum line and were more active against the chloroquine- and mefloquine-resistant (Dd2) P. falciparum line. All compounds are "Rule-of-5" compliant, and we show that metabolic stability can be enhanced via modification at either the primary or pyrrole nitrogen. These promising results lay the foundation for the development of this structurally unprecedented natural product.