2-O-Methylascochlorin | 38561-39-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 2-O-Methylascochlorin
• 英文别名: 5-chloro-4-hydroxy-2-methoxy-6-methyl-3-[(2E,4E)-3-methyl-5-[(1R,2R,6R)-1,2,6-trimethyl-3-oxocyclohexyl]penta-2,4-dienyl]benzaldehyde
• CAS: 38561-39-6
• 化学式: C₂₄H₃₁ClO₄
• 分子量: 418.961
• InChiKey: AVSKESKHZOLKTC-UMXIGZEWSA-N

物化性质

• 沸点：
  547.0±50.0 °C(Predicted)
• 密度：
  1.153±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-O-Methylascochlorin 在 sodium hydride 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 4-O-Carboxymethyl-2-O-methylascochlorin
  参考文献：
  名称：

  Ascochlorin Derivatives as Ligands for Nuclear Hormone Receptors

  摘要：

  Nuclear receptor family proteins are structurally related transcription factors activated by specific lipophilic compounds. Because they are activated by a variety of hormonal molecules, including retinoic acid, vitamin D, and steroid hormones, they are assumed to be promising targets for clinical drugs. We previously found that one ascochlorin (1) derivative, 4-O-carboxymethyl-ascochlorin (2), is a potent agonist of peroxisome proliferator activated receptor gamma (PPARgamma). Here, we synthesized derivatives of 1, designated as a lead compound, to create new modulators of nuclear hormone receptors. Two derivatives, 4-O-carboxymethyl-2-O-methylascochlorin (9) and 4-O-isonicotinoyl-2-O-methylasco(hlorin (10), showed improved agonistic activity for PPARgamma and induced differentiation of a progenitor cell line, C3HIOT1/2. We also found that 1, dehydroascofuranon (29), and a 2,4-0-diacetyl-1-carboxylic acid derivative of 1 (5) specifically activated estrogen receptors, PPARalpha, and an androgen receptor. All of the derivatives (1-29) activated the pregnane X receptor. These results suggest that the chemical structure of 1 is useful in designing novel modulators of nuclear receptors.

  DOI：

  10.1021/jm0205649
• 作为产物：
  描述：

  壳二孢氯素 在 吡啶 、 sodium hydroxide 、 potassium carbonate 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 4.0h， 生成 2-O-Methylascochlorin
  参考文献：
  名称：

  Ascochlorin Derivatives as Ligands for Nuclear Hormone Receptors

  摘要：

  Nuclear receptor family proteins are structurally related transcription factors activated by specific lipophilic compounds. Because they are activated by a variety of hormonal molecules, including retinoic acid, vitamin D, and steroid hormones, they are assumed to be promising targets for clinical drugs. We previously found that one ascochlorin (1) derivative, 4-O-carboxymethyl-ascochlorin (2), is a potent agonist of peroxisome proliferator activated receptor gamma (PPARgamma). Here, we synthesized derivatives of 1, designated as a lead compound, to create new modulators of nuclear hormone receptors. Two derivatives, 4-O-carboxymethyl-2-O-methylascochlorin (9) and 4-O-isonicotinoyl-2-O-methylasco(hlorin (10), showed improved agonistic activity for PPARgamma and induced differentiation of a progenitor cell line, C3HIOT1/2. We also found that 1, dehydroascofuranon (29), and a 2,4-0-diacetyl-1-carboxylic acid derivative of 1 (5) specifically activated estrogen receptors, PPARalpha, and an androgen receptor. All of the derivatives (1-29) activated the pregnane X receptor. These results suggest that the chemical structure of 1 is useful in designing novel modulators of nuclear receptors.

  DOI：

  10.1021/jm0205649

文献信息

• EP1481670
  申请人：——

  公开号：——

  公开（公告）日：——
• Ascochlorin Derivatives as Ligands for Nuclear Hormone Receptors
  作者：Marie Togashi、Satoshi Ozawa、Shoko Abe、Tomoyuki Nishimura、Mie Tsuruga、Kunio Ando、Gakuzo Tamura、Shigefumi Kuwahara、Makoto Ubukata、Junji Magae

  DOI：10.1021/jm0205649

  日期：2003.9.1

  Nuclear receptor family proteins are structurally related transcription factors activated by specific lipophilic compounds. Because they are activated by a variety of hormonal molecules, including retinoic acid, vitamin D, and steroid hormones, they are assumed to be promising targets for clinical drugs. We previously found that one ascochlorin (1) derivative, 4-O-carboxymethyl-ascochlorin (2), is a potent agonist of peroxisome proliferator activated receptor gamma (PPARgamma). Here, we synthesized derivatives of 1, designated as a lead compound, to create new modulators of nuclear hormone receptors. Two derivatives, 4-O-carboxymethyl-2-O-methylascochlorin (9) and 4-O-isonicotinoyl-2-O-methylasco(hlorin (10), showed improved agonistic activity for PPARgamma and induced differentiation of a progenitor cell line, C3HIOT1/2. We also found that 1, dehydroascofuranon (29), and a 2,4-0-diacetyl-1-carboxylic acid derivative of 1 (5) specifically activated estrogen receptors, PPARalpha, and an androgen receptor. All of the derivatives (1-29) activated the pregnane X receptor. These results suggest that the chemical structure of 1 is useful in designing novel modulators of nuclear receptors.