[1-(4-chloro-benzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]-acetic acid 4-[2-(diethoxy-phosphoryloxy)-ethyl]-phenyl ester | 1428774-23-5

• 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: [1-(4-chloro-benzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]-acetic acid 4-[2-(diethoxy-phosphoryloxy)-ethyl]-phenyl ester
• 英文别名: [1-(4-Chloro-benzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]-acetic acid 4-[2-(diethoxy-phosphoryloxy)-ethyl]-phenyl ester；[4-(2-diethoxyphosphoryloxyethyl)phenyl] 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetate
• CAS: 1428774-23-5
• 化学式: C₃₁H₃₃ClNO₈P
• 分子量: 614.032
• InChiKey: ROOLOBPDQSZRCB-UHFFFAOYSA-N

物化性质

• 沸点：
  682.5±55.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  42
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  102
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [1-(4-chloro-benzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]-acetic acid 4-[2-(diethoxy-phosphoryloxy)-ethyl]-phenyl ester 在 glucose-6-phosphate dehydrogenase 、 3-氟-4-甲氧基苯乙酮 、 glucose 6-phosphate 、 human recombinant cytochrome P₄₅₀ 2D₆ 、 烟酰胺腺嘌呤双核苷酸磷酸盐 、 magnesium chloride 作用下， 以 aq. phosphate buffer 为溶剂， 反应 1.0h， 生成 4-(2-((diethoxyphosphoryl)oxy)ethyl)phenyl 2-(1-(4-chlorobenzoyl)-5-hydroxy-2-methyl-1H-indol-3-yl)acetate
  参考文献：
  名称：

  小鼠、大鼠和人对磷酸-酪醇-吲哚美辛的体外代谢比较。

  摘要：

  Phospho-tyrosol-indomethacin (PTI; MPI 621) 是一种新型抗癌剂，比传统的吲哚美辛更有效、更安全。在这里，我们表明 PTI 在体外和体内都被广泛代谢。PTI 被羧酸酯酶迅速水解，生成吲哚美辛作为其在肝微粒体和大鼠中的主要代谢物。PTI 还在其酪醇部分经历细胞色素 P450 (CYP) 介导的羟基化，并在其吲哚美辛部分经历 O-去甲基化。五种主要的人类CYPs中，CYP3A4和CYP2D6分别催化PTI的羟基化和O-去甲基化反应；而 CYP1A2、2C9 和 2C19 对 PTI 无活性。与 PTI 相比，吲哚美辛主要被 CYP2C9 进行 O-去甲基化，后者更喜欢酸性底物。PTI 的水解和 O-去甲基化代谢物进一步被葡萄糖醛酸化和硫酸化，促进药物清除和解毒。我们观察到 PTI 代谢率的显着种间差异。在来自不同物种的肝微粒体中，PTI 分别在小鼠、人类和大鼠肝微粒体中水解、羟基化和

  DOI：

  10.1016/j.bcp.2013.01.031
• 作为产物：
  描述：

  [1-(4-chloro-benzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]-acetic acid 4-(2-hydroxy-ethyl)-phenyl ester 、 氯磷酸二乙酯 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以82%的产率得到[1-(4-chloro-benzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]-acetic acid 4-[2-(diethoxy-phosphoryloxy)-ethyl]-phenyl ester
  参考文献：
  名称：

  PHOSPHO-ESTER DERIVATIVES AND USES THEREOF

  摘要：

  磷酸酯化合物及其制剂可通过呼吸道及其他途径用于预防和/或治疗肺癌和脑癌及其癌前病变条件，用于疼痛治疗，用于皮肤疾病治疗，用于治疗和/或预防与炎症相关的疾病，以及用于癌症的治疗和预防。

  公开号：

  US20130225529A1

文献信息

• COMPOUNDS AND COMPOSITIONS FOR USE IN THE TREATMENT AND PREVENTION OF LUNG AND BRAIN CANCER AND PRECANCEROUS CONDITIONS THEREOF
  申请人：Medicon Pharmaceuticals, Inc.

  公开号：US20140178461A1

  公开（公告）日：2014-06-26

  Novel compounds and pharmaceutical compositions thereof administered by the respiratory route for prevention and/or treatment of lung and brain cancer and precancerous conditions thereof.

  通过呼吸道给予的新化合物和其制药组合物，用于预防和/或治疗肺癌、脑癌及其癌前状态。
• PRODUCT COMPRISING A NICOTINE-CONTAINING MATERIAL AND AN ANTI-CANCER AGENT
  申请人：Rigas Basil

  公开号：US20140088045A1

  公开（公告）日：2014-03-27

  The present invention provides a composition comprising a nicotine-containing material and an anti-cancer agent usable in the treatment and/or prevention or reduction of the risk of cancer and precancerous conditions as well as for preventing or reducing the risk of cancer recurrence. Furthermore, a composition comprising a nicotine-containing material and an anti-inflammatory agent usable in the treatment and/or prevention or reduction of the risk of inflammation, is provided. The nicotine containing composition can also include both an anti-cancer agent and an anti-inflammatory agent A device for administering the composition of the present invention to subjects can be a cigarette, smoking pipe, smokeless tobacco, electronic cigarette, transdermal patch or the like.
• COMPOUNDS AND COMPOSITIONS FOR USE IN THE PREVENTION AND TREATMENT OF INFLAMMATION-RELATED DISORDERS, PAIN AND FEVER, SKIN DISORDERS, CANCER AND PRECANCEROUS CONDITIONS THEREOF
  申请人：Medicon Pharmaceuticals, Inc.

  公开号：US20140315834A1

  公开（公告）日：2014-10-23

  The present invention provides novel compounds and pharmaceutical compositions for the prevention and/or treatment of cancer and precancerous conditions thereof, for the treatment of pain and fever, for the treatment of skin disorders, and for treating and/or preventing inflammation-related diseases and/or cardiovascular diseases. The compounds of the invention also have analgesic properties and anti-platelet properties. The compounds of the invention may be provided to animals, including mammals and humans, by administering a suitable pharmaceutical dose in a suitable pharmaceutical dosage form. The compounds of the invention have improved efficacy and safety, including higher potency and/or fewer or less severe side effects, than conventional therapies. The compounds of the invention comprise a biologically active moiety or portion (A) that has, or is modified to have at least one carboxyl group. The moiety A is preferably an aliphatic, aromatic or alkylaryl group, preferably derived from a non-steroidal anti-inflammatory drug or NSAID (A). The moiety A is bound to a linker moiety (B) via the carboxyl of group A and a linking atom that is selected from oxygen, nitrogen, and sulphur, to form a carboxylic ester, and amide, or a thioester, bond (X 1 ) between groups A and B. Moiety B is a single bond, an aliphatic group, a substituted benzene, or an alkylene substituted hydrocarbon chain, which in turn is bound to functional moiety Z, which facilitates access of the compound into cells. The moiety Z can comprise, for example, a phosphorous-containing group, a nitrogen-containing group, or a folic acid residue.
• [EN] PHOSPHO-ESTER DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS DE PHOSPHO-ESTER ET LEURS UTILISATIONS
  申请人：RIGAS BASIL

  公开号：WO2013130625A1

  公开（公告）日：2013-09-06

  Phospho-ester compounds and pharmaceutical compositions thereof administered by the respiratory and other routes for the prevention and/or treatment of lung and brain cancer and precancerous conditions thereof, for the treatment of pain, for the treatment of skin disorders, for treating and/or preventing inflammation-related diseases, and for the treatment and prevention of cancer.
• [EN] METHODS OF TREATING PROLIFERATIVE DISORDERS<br/>[FR] PROCEDES DE TRAITEMENT DE TROUBLES PROLIFERATIFS
  申请人：RIGAS BASIL

  公开号：WO2014172315A2

  公开（公告）日：2014-10-23

  The invention is based on the discovery that elevated levels of oxidative stress shortly after administration of chemotherapeutic or radiation therapy in subjects having proliferative disorders is indicative of sensitivity to the administered chemotherapeutic or radiation therapy. Consequently, measurement of oxidative stress biomarker levels can inform whether a particular chemotherapeutic or radiation therapy is likely to be efficacious in treating a proliferative disorder before prolonged exposure to the therapy. This information allows a subject to avoid unnecessary and otherwise dangerous therapies and increases the likelihood that a selected therapeutic course will ultimately lead to treatment of a particular proliferative disorder.