ethyl 3-(L-2-N,N-dimethylamino-3-phenyl-propanoyloxy)-3-(pyridin-4-yl)-propanoate | 1026885-94-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl 3-(L-2-N,N-dimethylamino-3-phenyl-propanoyloxy)-3-(pyridin-4-yl)-propanoate
• 英文别名: (S)-3-Ethoxy-3-oxo-1-(pyridin-4-yl)propyl dimethyl-L-phenylalaninate；[(1S)-3-ethoxy-3-oxo-1-pyridin-4-ylpropyl] (2S)-2-(dimethylamino)-3-phenylpropanoate
• CAS: 1026885-94-8
• 化学式: C₂₁H₂₆N₂O₄
• 分子量: 370.448
• InChiKey: UPEGTKGIJKFNNL-OALUTQOASA-N

物化性质

• 沸点：
  466.0±45.0 °C(Predicted)
• 密度：
  1.144±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  27
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  68.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 3-(L-2-N,N-dimethylamino-3-phenyl-propanoyloxy)-3-(pyridin-4-yl)-propanoate 在 吡啶 、 lithium aluminium tetrahydride 、 叔丁基氯化镁 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 37.5h， 生成 4-氨基-1-[5-O-[(2R,4S)-2-氧代-4-(4-吡啶基)-1,3,2-二氧磷杂环己烷-2-基]-BETA-D-呋喃阿拉伯糖基]-2(1H)-嘧啶酮
  参考文献：
  名称：

  Synthesis and Characterization of a Novel Liver-Targeted Prodrug of Cytosine-1-β-d-arabinofuranoside Monophosphate for the Treatment of Hepatocellular Carcinoma

  摘要：

  Cytotoxic nucleosides have proven to be ineffective for the treatment of hepatocellular carcinoma (HCC) due, in part, to their inadequate conversion to their active nucleoside triphosphates (NTP) in the liver tumor and high conversion in other tissues. These characteristics lead to poor efficacy, high toxicity, and a drug class associated with an unacceptable therapeutic index. Cyclic 1-aryl-1,3-propanyl phosphate prodrugs selectively release the monophosphate of a nucleoside (NMP) into CYP3A4-expressing cells, such as hepatocytes, while leaving the prodrug intact in plasma and extrahepatic tissues. This prodrug strategy was applied to the monophosphate of the well-known cytotoxic nucleoside cytosine-1-beta-D-arabinofuranoside (cytarabine, araC). Compound 19S (MB07133), in mice, achieves good liver targeting compared to araC, generating > 19-fold higher cytarabine triphosphate (araCTP) levels in the liver than levels of araC in the plasma and > 12-fold higher araCTP levels in the liver than in the bone marrow, representing a > 120-fold and > 28-fold improvement, respectively, over araC administration.

  DOI：

  10.1021/jm0607449
• 作为产物：
  描述：

  4-吡啶甲醛 在 4-二甲氨基吡啶 、 正丁基锂 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 二异丙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 9.25h， 生成 ethyl 3-(L-2-N,N-dimethylamino-3-phenyl-propanoyloxy)-3-(pyridin-4-yl)-propanoate
  参考文献：
  名称：

  用于代谢性疾病治疗的化合物及其制备方法 和应用

  摘要：

  本发明提供了一种用于代谢性疾病治疗的化合物，具有式(I)或式(Ⅱ)所示结构，或其消旋体，立体异构体，几何异构体，互变异构体，溶剂化物，水合物，代谢产物，药学上可接受的盐或其前药。本发明提供的化合物为FXR和/或TGR5受体激活物，其具有激活FXR和/或TGR5受体活性，可用于制备治疗慢性肝病、代谢性疾病或门脉高压症的药物。

  公开号：

  CN109929005B

文献信息

• COMPOUND FOR TREATING METABOLIC DISEASES AND PREPARATION METHOD AND USE THEREOF
  申请人：Xi' An Biocare Pharma

  公开号：EP3730509A1

  公开（公告）日：2020-10-28

  Provided are a compound for treating metabolic diseases having the structure as shown in formula (I) or formula (II), or a racemate, stereoisomer, geometric isomer, tautomer, solvate, hydrate, metabolite, pharmaceutically acceptable salt or prodrug thereof. The compound is an activator of FXR and/or a TGR5 receptor, and thus has the activity of activating FXR and/or a TGR5 receptor, and can be used in the preparation of drugs for treating chronic liver diseases, metabolic diseases or portal hypertension.

  本发明提供了一种治疗代谢性疾病的化合物，其结构如式（I）或式（II）所示，或其外消旋体、立体异构体、几何异构体、同分异构体、溶解物、水合物、代谢物、药学上可接受的盐或原药。该化合物是 FXR 和/或 TGR5 受体的激活剂，因此具有激活 FXR 和/或 TGR5 受体的活性，可用于制备治疗慢性肝病、代谢性疾病或门脉高压症的药物。
• Compound for treating metabolic diseases and preparation method and use thereof
  申请人：Xi' An Biocare Pharma Ltd.

  公开号：US11028111B2

  公开（公告）日：2021-06-08

  Provided are a compound for treating metabolic diseases having the structure as shown in formula (I) or formula (II), or a racemate, stereoisomer, geometric isomer, tautomer, solvate, hydrate, metabolite, pharmaceutically acceptable salt or prodrug thereof. The compound is an activator of FXR and/or a TGR5 receptor, and thus has the activity of activating FXR and/or a TGR5 receptor, and can be used in the preparation of drugs for treating chronic liver diseases, metabolic diseases or portal hypertension.

  本发明提供了一种治疗代谢性疾病的化合物，其结构如式（I）或式（II）所示，或其外消旋体、立体异构体、几何异构体、同分异构体、溶解物、水合物、代谢物、药学上可接受的盐或原药。该化合物是 FXR 和/或 TGR5 受体的激活剂，因此具有激活 FXR 和/或 TGR5 受体的活性，可用于制备治疗慢性肝病、代谢性疾病或门脉高压症的药物。