2-(4-methyl-7-oxo-(1α-H),2,3,(4β-H),(4aα-H),5,6,7,8,(8α-H)-decahydronaphthalen-1-yl)propionic acid methyl ester

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 2-(4-methyl-7-oxo-(1α-H),2,3,(4β-H),(4aα-H),5,6,7,8,(8α-H)-decahydronaphthalen-1-yl)propionic acid methyl ester
• 英文别名: methyl (2R)-2-[(1R,4R,4aS,8aS)-4-methyl-7-oxo-2,3,4,4a,5,6,8,8a-octahydro-1H-naphthalen-1-yl]propanoate
• 化学式: C₁₅H₂₄O₃
• 分子量: 252.354
• InChiKey: IRABTPPADYCWNQ-JHYOHUSXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-methyl-7-oxo-(1α-H),2,3,(4β-H),(4aα-H),5,6,7,8,(8α-H)-decahydronaphthalen-1-yl)propionic acid methyl ester 在 4-二甲氨基吡啶 、 lithium hydroxide monohydrate 、 sodium hydride 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 26.0h， 生成 (R)-N-(4-chloro-3-(pyridin-2-yl)phenyl)-2-((4aS,5R,8-R,8aS)-5-methyl-1-phenyl-4,4a,5,6,7,8,8a,9-octahydro-1H-benzo[f ]-indazol-8-yl)propanamide
  参考文献：
  名称：

  Design, Synthesis, and Pharmacological Evaluation of 2-(2,5-Dimethyl-5,6,7,8-tetrahydroquinolin-8-yl)-N-aryl Propanamides as Novel Smoothened (Smo) Antagonists

  摘要：

  A series of novel Smo antagonists were developed either by directly incorporating the basic skeleton of the natural product artemisinin or by first breaking artemisinin into structurally simpler and stable intermediates and then reconstructing into diversified heterocyclic derivatives, equipped with a Smo-targeting bullet. 2-(2,5-Dimethy1-5,6,7,8-tetrahydroquinolin-8-yl)-N-arylpropanamide 65 was identified as the most potent, with an IC50 value of 9.53 nM against the Hh signaling pathway. Complementary mechanism studies confirmed that 65 inhibits Hh signaling pathway by targeting Smo and shares the same binding site as that of the tool drug cyclopamine. Meanwhile, 65 has a good plasma exposure and an acceptable oral bioavailability. Dose-dependent antiproliferative effects were observed in ptch+/;p53-/- medulloblastoma cells, and significant tumor growth inhibitions were achieved for 65 in the ptch+/-;p53-/- medulloblastoma allograft model.

  DOI：

  10.1021/acs.jmedchem.6b01247
• 作为产物：
  描述：

  青蒿素 在 barium hydroxide octahydrate 、 硫酸 、 palladium on activated charcoal 、 氢气 、 potassium carbonate 作用下， 以 甲醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.83h， 生成 2-(4-methyl-7-oxo-(1α-H),2,3,(4β-H),(4aα-H),5,6,7,8,(8α-H)-decahydronaphthalen-1-yl)propionic acid methyl ester
  参考文献：
  名称：

  Design, Synthesis, and Pharmacological Evaluation of 2-(2,5-Dimethyl-5,6,7,8-tetrahydroquinolin-8-yl)-N-aryl Propanamides as Novel Smoothened (Smo) Antagonists

  摘要：

  A series of novel Smo antagonists were developed either by directly incorporating the basic skeleton of the natural product artemisinin or by first breaking artemisinin into structurally simpler and stable intermediates and then reconstructing into diversified heterocyclic derivatives, equipped with a Smo-targeting bullet. 2-(2,5-Dimethy1-5,6,7,8-tetrahydroquinolin-8-yl)-N-arylpropanamide 65 was identified as the most potent, with an IC50 value of 9.53 nM against the Hh signaling pathway. Complementary mechanism studies confirmed that 65 inhibits Hh signaling pathway by targeting Smo and shares the same binding site as that of the tool drug cyclopamine. Meanwhile, 65 has a good plasma exposure and an acceptable oral bioavailability. Dose-dependent antiproliferative effects were observed in ptch+/;p53-/- medulloblastoma cells, and significant tumor growth inhibitions were achieved for 65 in the ptch+/-;p53-/- medulloblastoma allograft model.

  DOI：

  10.1021/acs.jmedchem.6b01247

文献信息

• Synthesis of labelled dihydroartemisinic acid
  作者：Geoffrey D Brown、Lai-King Sy

  DOI：10.1016/j.tet.2003.11.069

  日期：2004.1

  [15-13C2H3]-Dihydroartemisinic acid (2a), [15-C2H3]-dihydroartemisinic acid (2b) and [15-13CH3]-dihydroartemisinic acid (2c) have been obtained in good yield and high isotopic enrichment by a reconstructive synthesis from artemisinin. These labelled compounds were designed to be used in biosynthetic experiments to determine the origins of artemisinin and other sesquiterpene natural products from Artemisia

  [15- 13 c ^ 2 ^ h 3 ] -二氢青蒿酸（图2a），[15-C 2 H ^ 3 ] -二氢青蒿酸（图2b）和[15- 13 CH 3 ] -二氢青蒿酸（2C）已经以良好的收率获得通过青蒿素的重组合成实现高同位素富集。这些标记的化合物被设计用于生物合成实验，以确定青蒿素和其他来自青蒿的倍半萜烯天然产物的来源。
• Design, Synthesis, and Pharmacological Evaluation of 2-(2,5-Dimethyl-5,6,7,8-tetrahydroquinolin-8-yl)-<i>N</i>-aryl Propanamides as Novel Smoothened (Smo) Antagonists
  作者：Gang Liu、Ding Xue、Jun Yang、Juan Wang、Xiaohua Liu、Wenjing Huang、Jie Li、Ya-Qiu Long、Wenfu Tan、Ao Zhang

  DOI：10.1021/acs.jmedchem.6b01247

  日期：2016.12.22

  A series of novel Smo antagonists were developed either by directly incorporating the basic skeleton of the natural product artemisinin or by first breaking artemisinin into structurally simpler and stable intermediates and then reconstructing into diversified heterocyclic derivatives, equipped with a Smo-targeting bullet. 2-(2,5-Dimethy1-5,6,7,8-tetrahydroquinolin-8-yl)-N-arylpropanamide 65 was identified as the most potent, with an IC50 value of 9.53 nM against the Hh signaling pathway. Complementary mechanism studies confirmed that 65 inhibits Hh signaling pathway by targeting Smo and shares the same binding site as that of the tool drug cyclopamine. Meanwhile, 65 has a good plasma exposure and an acceptable oral bioavailability. Dose-dependent antiproliferative effects were observed in ptch+/;p53-/- medulloblastoma cells, and significant tumor growth inhibitions were achieved for 65 in the ptch+/-;p53-/- medulloblastoma allograft model.