2-(4-methyl-7-oxo-(1α-H),2,3,(4β-H),(4aα-H),5,6,7,8,(8aα-H)-decahydronaphthalen-1-yl)propionic acid | 103740-02-9

• 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,(8aα-H)-decahydronaphthalen-1-yl)propionic acid
• 英文别名: 1R-<1α(R*),4β,4aβ,8aβ>-α,4-dimethyl-decahydro-7-oxo-1-naphthaleneacetic acid；<1(R),4a(S),8a(S)>-decahydro-4(R)-methyl-7-oxo-α(R)-methylnaphthaleneaxetic acid；(2R)-2-[(1R,4R,4aS,8aS)-4-methyl-7-oxo-2,3,4,4a,5,6,8,8a-octahydro-1H-naphthalen-1-yl]propanoic acid
• CAS: 103740-02-9
• 化学式: C₁₄H₂₂O₃
• 分子量: 238.327
• InChiKey: ZVUUTVARYFEWPE-QVWLAYSOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 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,(8aα-H)-decahydronaphthalen-1-yl)propionic acid 在 lithium hydroxide monohydrate 、 potassium hydroxide 作用下， 以 乙醇 、 水 、 溶剂黄146 、 二甲基亚砜 为溶剂， 反应 17.0h， 生成
  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 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 10.33h， 生成 2-(4-methyl-7-oxo-(1α-H),2,3,(4β-H),(4aα-H),5,6,7,8,(8aα-H)-decahydronaphthalen-1-yl)propionic acid
  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。
• A Novel Asymmetric Total Synthesis of (+)-Artemisinin
  作者：Mauricio Gomes Constantino、Milton Beltrame、Gil Valdo José da Silva、Julio Zukerman-Schpector

  DOI：10.1080/00397919608003621

  日期：1996.1

  A 12-step synthesis of the natural product (+)-Artemisinin, very active against malaria, is described. (-)-Isopulegol, which already contains two of the asymmetric centers of (+)-Artemisinin in the correct absolute configuration, was used as starting material.
• Crystal structure of an intermediate in the synthesis of artemisinin
  作者：J. Zukerman-Schpector、Mauricio G. Constantino、Milton Beltrame

  DOI：10.1007/bf01665279

  日期：1995.7

  C(14)H(22)O(3)r M(tau) = 238.33, P2(1)2(1)2(1), Z = 4, a = 6.892(2), b = 11.453(1), c = 17.159(5) Angstrom. [1R - [1 alpha(R*), 4 beta, 4a beta, 8a beta]] - alpha,4-Dimethyl-decahydro-7-oxo-1-naphtaleneacetic acid. The cyclohexane ring adopts a chair conformation and the cis-fused cyclohexanone ring is in a slightly distorted chair conformation. The molecular packing involves an hydrogen bond and C-H ... O contacts.
• 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.