1-(pyridin-3-yl)-1,3-propanediol | 123016-77-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-(pyridin-3-yl)-1,3-propanediol
• 英文别名: 1-(Pyridin-3-yl)propane-1,3-diol；1-pyridin-3-ylpropane-1,3-diol
• CAS: 123016-77-3
• 化学式: C₈H₁₁NO₂
• 分子量: 153.181
• InChiKey: XFFAGZSKGVYMBR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  53.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(pyridin-3-yl)-1,3-propanediol 在 叔丁基氯化镁 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 22.0h， 生成
  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-羟基-3-(吡啶-3-基)丙酸乙酯 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 生成 1-(pyridin-3-yl)-1,3-propanediol
  参考文献：
  名称：

  Pradefovir: A Prodrug That Targets Adefovir to the Liver for the Treatment of Hepatitis B

  摘要：

  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.

  DOI：

  10.1021/jm7012216

文献信息

• [EN] A PRODRUG PLATFORM USEFUL TO DELIVER AMINES, AMIDES AND PHENOLS<br/>[FR] PLATE-FORME DE PROMÉDICAMENTS UTILE POUR ADMINISTRER DES AMINES, DES AMIDES ET DES PHÉNOLS
  申请人：SHANGHAI CHANGCHENGYIYAOKEJI COMPANY LTD

  公开号：WO2021032075A1

  公开（公告）日：2021-02-25

  Provided herein is a prodrug platform useful to deliver pharmaceutically active amines, amides and phenols and their use in the diagnosis, prevention and/or treatment of various diseases. Compared with the parent drug (e.g., Gemcitabine), the prodrugs show a significant overall safety improvement (therapeutic index (TI) improvement), especially in liver.

  本文提供了一种用于传递药用活性胺、酰胺和酚的前药平台，以及它们在诊断、预防和/或治疗各种疾病中的用途。与母药（例如吉西他滨）相比，前药在整体安全性方面表现出明显改善（疗效指数（TI）改善），尤其是在肝脏方面。
• [EN] PHOSPHORUS-CONTAINING PRODRUGS OF GEMCITABINE<br/>[FR] PROMÉDICAMENTS CONTENANT DU PHOSPHORE DE GEMCITABINE
  申请人：SHANGHAI CHANGCHENGYIYAOKEJI COMPANY LTD

  公开号：WO2020001475A1

  公开（公告）日：2020-01-02

  This invention relates to phosphorus-containing prodrugs of gemcitabine and their use in the treatment of cancer and viral infectious diseases. Compared with the parent drug (i.e., Gemcitabine), the prodrugs of present invention show a significant overall safety improvement (therapeutic index (TI) improvement), especially in liver.

  这项发明涉及含磷前药的吉西他滨及其在癌症和病毒感染性疾病治疗中的应用。与母药（即吉西他滨）相比，本发明的前药在整体安全性方面表现出显著改善（治疗指数（TI）改善），尤其是在肝脏方面。
• [EN] PIPECOLATE-SULFONAMIDES FOR TREATMENT OF PSYCHIATRIC DISORDERS<br/>[FR] PIPÉCOLATE-SULFONAMIDES POUR LE TRAITEMENT DE TROUBLES PSYCHIATRIQUES
  申请人：MAX PLANCK GESELLSCHAFT

  公开号：WO2013097947A1

  公开（公告）日：2013-07-04

  The present invention relates to compounds having a pipecolate sulfonamide scaffold, pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing at least one of these compounds together with pharmaceutically acceptable carrier, excipient and/or diluents. Said pipecolate sulfonamide compounds can be used for prophylaxis and/or treatment of psychiatric disorders and neurodegenerative diseases, disorders and conditions.

  本发明涉及具有吡哌酸磺胺基骨架的化合物，这些化合物的药用盐以及含有至少一种这些化合物的药用载体、赋形剂和/或稀释剂的药物组合物。所述的吡哌酸磺胺基化合物可用于预防和/或治疗精神障碍和神经退行性疾病、紊乱和状况。
• Pipecolate-sulfonamides for treatment of psychiatric disorders
  申请人：Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.

  公开号：EP2610245A1

  公开（公告）日：2013-07-03

  The present invention relates to compounds having a pipecolate sulfonamide scaffold, pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing at least one of these compounds together with pharmaceutically acceptable carrier, excipient and/or diluents. Said pipecolate sulfonamide compounds can be used for prophylaxis and/or treatment of psychiatric disorders and neurodegenerative diseases, disorders and conditions.

  本发明涉及具有吡啶甲酸磺酰胺骨架的化合物，这些化合物的药用盐以及含有至少一种这些化合物的药用载体、赋形剂和/或稀释剂的药物组合物。所述的吡啶甲酸磺酰胺化合物可用于预防和/或治疗精神障碍和神经退行性疾病、障碍和症状。
• PIPECOLATE-SULFONAMIDES FOR TREATMENT OF PSYCHIATRIC DISORDERS
  申请人：Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.

  公开号：US20150011541A1

  公开（公告）日：2015-01-08

  The present invention relates to compounds having a pipecolate sulfonamide scaffold, pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing at least one of these compounds together with pharmaceutically acceptable carrier, excipient and/or diluents. Said pipecolate sulfonamide compounds can be used for prophylaxis and/or treatment of psychiatric disorders and neurodegenerative diseases, disorders and conditions.

  本发明涉及具有pipecolate磺酰胺支架的化合物，这些化合物的药学可接受盐以及含有至少一种这些化合物和药学可接受的载体、赋形剂和/或稀释剂的制药组合物。所述pipecolate磺酰胺化合物可用于预防和/或治疗精神障碍和神经退行性疾病、疾病和病况。