3-羟基-3-(吡啶-3-基)丙酸乙酯 | 591228-12-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 中文名称: 3-羟基-3-(吡啶-3-基)丙酸乙酯
• 英文名称: Ethyl 3-hydroxy-3-(3-pyridinyl) propanoate
• 英文别名: Ethyl-3-hydroxy-3-(3-pyridinyl)propanoat；Ethyl 3-hydroxy-3-(pyridin-3-yl)propanoate；ethyl 3-hydroxy-3-pyridin-3-ylpropanoate
• CAS: 591228-12-5
• 化学式: C₁₀H₁₃NO₃
• mdl: MFCD08442893
• 分子量: 195.218
• InChiKey: YHUNNSMSEATGJD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  59.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-羟基-3-(吡啶-3-基)丙酸乙酯 在 sodium tetrahydroborate 、 叔丁基氯化镁 、 四乙基氟化铵水合物 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 40.0h， 生成 5'-O-trans-[4-(pyridin-3-yl)-2-oxido-1,3,2-dioxaphosphorinan-2yl]-cytosine-β-D-arabinofuranoside
  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：

  3-吡啶甲醛 、 乙酸乙酯 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 3.0h， 生成 3-羟基-3-(吡啶-3-基)丙酸乙酯
  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

文献信息

• Process for reducing 3-heteroaryl-3-oxopropionic acid derivatives
  申请人：——

  公开号：US20030225274A1

  公开（公告）日：2003-12-04

  The present invention relates to a process for preparing stereoisomerically enriched 3-heteroaryl-3-hydroxycarboxylic esters by reducing 3-heteroaryl-3-oxocarboxylic esters in the presence of ruthenium-containing catalysts.

  本发明涉及一种在含有钌催化剂的情况下还原3-杂环基-3-酮羧酸酯以制备立体异构富集的3-杂环基-3-羟基羧酸酯的方法。
• Process for preparing 3-heteroaryl-3-hydroxypropanoic acid derivatives
  申请人：Berendes Frank

  公开号：US20060264641A1

  公开（公告）日：2006-11-23

  The invention relates to a process for preparing enantiomer-enriched 3-heteroaryl-3-hydroxypropanoic acid derivatives and 3-heteroaryl-1-aminopropan-3-ols, and to their use.

  本发明涉及一种制备对映富集的3-杂环基-3-羟基丙酸衍生物和3-杂环基-1-氨基丙醇的方法，以及它们的应用。
• Verfahren zur Reduktion von 3-Heteroaryl-3-Oxopropionsäurederivaten
  申请人：BAYER AG

  公开号：EP1340746A1

  公开（公告）日：2003-09-03

  Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung stereoisomerenangereicherter 3-Heteroaryl-3-hydroxycarbonsäureester durch Reduktion von 3-Heteroaryl-3-oxocarbonsäureestern in Gegenwart von Ruthenium enthaltenden Katalysatoren.

  本发明涉及一种在含钌催化剂存在下通过还原 3-heteroaryl-3-oxocarboxylic acid esters 制备立体异构体丰富的 3-heteroaryl-3-hydroxycarboxylic acid esters 的工艺。
• Pradefovir: A Prodrug That Targets Adefovir to the Liver for the Treatment of Hepatitis B
  作者：K. Raja Reddy、Michael C. Matelich、Bheemarao G. Ugarkar、Jorge E. Gómez-Galeno、Jay DaRe、Kristin Ollis、Zhili Sun、William Craigo、Timothy J. Colby、James M. Fujitaki、Serge H. Boyer、Paul D. van Poelje、Mark D. Erion

  DOI：10.1021/jm7012216

  日期：2008.2.1

  Adefovir dipivoxil, a marketed drug for the treatment of hepatitis B, is dosed at submaximally efficacious doses because of renal toxicity. In an effort to improve the therapeutic index of adefovir, 1-aryl-1,3-propanyl prodrugs were synthesized with the rationale that this selectively liver-activated prodrug class would enhance liver levels of the active metabolite adefovir diphosphate (ADV-DP) and/or decrease kidney exposure. The lead prodrug (14, MB06866, pradefovir), identified from a variety of in vitro and in vivo assays, exhibited good oral bioavailability (F = 42%, mesylate salt, rat) and rate of prodrug conversion to ADV-DP. Tissue distribution studies in the rat using radiolabeled materials showed that cyclic 1-aryl-1,3-propanyl prodrugs enhance the delivery of adefovir and its metabolites to the liver, with pradefovir exhibiting a 12-fold improvement in the liver/kidney ratio over adefovir dipivoxil.
• US8293899B2
  申请人：——

  公开号：US8293899B2

  公开（公告）日：2012-10-23