digoxin | 20830-75-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: digoxin
• 英文别名: 4-((3S,5R,8R,9S,10S,12R,13S,14S,17R)-3-((2R,4S,5S,6R)-5-((2S,4S,5S,6R)-5-((2S,4S,5S,6R)-4,5-dihydroxy-6-methyltetrahydro-2H-pyran-2-yloxy)-4-hydroxy-6-methyltetrahydro-2H-pyran-2-yloxy)-4-hydroxy-6-methyltetrahydro-2H-pyran-2-yloxy)-12,14-dihydroxy-10,13-；3-[(3S,5R,8R,9S,10S,12R,13S,14S)-3-[(2R,4S,5S,6R)-5-[(2S,4S,5S,6R)-5-[(2S,4S,5S,6R)-4,5-dihydroxy-6-methyloxan-2-yl]oxy-4-hydroxy-6-methyloxan-2-yl]oxy-4-hydroxy-6-methyloxan-2-yl]oxy-12,14-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one
• CAS: 20830-75-5；61436-59-7；96386-77-5
• 化学式: C₄₁H₆₄O₁₄
• 分子量: 780.951
• InChiKey: LTMHDMANZUZIPE-YUICGFAKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  55
• 可旋转键数：
  7
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  203
• 氢给体数：
  6
• 氢受体数：
  14

ADMET

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：由于母乳中地高辛含量较低，婴儿摄入的量很小，预计不会对哺乳婴儿造成任何不良影响。如果母亲需要静脉注射地高辛，剂量后避免哺乳2小时可以减少婴儿的摄入量。 ◉ 对哺乳婴儿的影响：至少有4项关于母乳中地高辛的研究报告称婴儿曾接受母乳喂养。无一发现可检测到的地高辛效应。[2][4][6] ◉ 对泌乳和母乳的影响：截至修订日期，未找到相关已发布信息。

◉ Summary of Use during Lactation:Because of the low levels of digoxin in breastmilk, amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants. If the mother is to receive digoxin intravenously, avoidance of breastfeeding for 2 hours after the dose will lessen the dose the infant receives. ◉ Effects in Breastfed Infants:At least 4 infants have been reported to have been breastfed in studies on digoxin in breastmilk. None had any detectable digoxin effect.[2][4][6] ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

反应信息

• 作为反应物：
  描述：

  digoxin 在 4-二甲氨基吡啶 、 2-乙氧基-1-乙氧碳酰基-1,2-二氢喹啉 、 N,N'-二环己基碳二亚胺 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 溶剂黄146 为溶剂， 反应 79.0h， 生成 4'''-(4-(methoxycarbonyl-2-(2S)-(4-hydroxyphenyl)ethyl)amino-4-oxobutanoyl)digoxin
  参考文献：
  名称：

  Preparation of 3-carboxypropanoates of digitoxin and digoxin and their conjugates with L-tyrosine

  摘要：

  地高辛和地高辛4'''-(3-羧基丙酸酯)(4'''-半琥珀酸酯) III 和 X 是通过间接方法制备的，使用二环己基碳二亚胺诱导的心糖苷与4-(2,2,2-三氯乙氧基)-4-氧代丁酸在二氯甲烷中在4-二甲基氨基吡啶或吡啶的存在下进行缩合，然后通过在四氢呋喃、乙酸和水的混合物中使用锌去除2,2,2-三氯乙基基团。半琥珀酸酯 III 和 X 与L-酪氨酸甲酯在四氢呋喃中缩合，使用N-乙氧甲酰-2-乙氧基-1,2-二氢喹啉作为偶联试剂。产物的结构通过¹H NMR和¹³C NMR光谱得到证实。缀合物 IV 和 XI 在L-酪氨酸部分标记了[¹²⁵I]。所获得的放射性配体 V 和 XII 被设计为心糖苷分析的RIA系统的一部分。

  DOI：

  10.1135/cccc19852760

文献信息

• Triple drug combination (metformin, simvastatin, digoxin) for targeted treatment of pancreatic cancer
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US10813909B2

  公开（公告）日：2020-10-27

  A combination of three well-known and FDA approved compounds has been discovered to significantly suppress the proliferation of pancreatic cancer cells in clinically relevant models of pancreatic cancer. Embodiments of the invention include compositions of matter comprising a combination of agents such as metformin, simvastatin, and digoxin as well as methods of treating cancers using such agents. Illustrative methods include combining a population of pancreatic cancer cells with amounts of metformin, simvastatin, and digoxin sufficient to inhibit expression of BIRC5 protein in the population of pancreatic cancer cells, thereby inhibiting the growth of the population of pancreatic cancer cells.

  在临床相关的胰腺癌模型中，发现了三种众所周知并经美国食品及药物管理局批准的化合物的组合能显著抑制胰腺癌细胞的增殖。本发明的实施方案包括由二甲双胍、辛伐他汀和地高辛等药物组合而成的物质组合物，以及使用此类药物治疗癌症的方法。说明性方法包括将胰腺癌细胞群与足以抑制胰腺癌细胞群中BIRC5蛋白表达的二甲双胍、辛伐他汀和地高辛结合，从而抑制胰腺癌细胞群的生长。
• TRIPLE DRUG COMBINATION (METFORMIN, SIMVASTATIN, DIGOXIN) FOR TARGETED TREATMENT OF PANCREATIC CANCER
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：EP3458033A2

  公开（公告）日：2019-03-27
• US9675623B2
  申请人：——

  公开号：US9675623B2

  公开（公告）日：2017-06-13
• [EN] TRIPLE DRUG COMBINATION (METFORMIN, SIMVASTATIN, DIGOXIN) FOR TARGETED TREATMENT OF PANCREATIC CANCER<br/>[FR] COMBINAISON DE TROIS MÉDICAMENTS (METFORMINE, SIMVASTATINE, DIGOXINE) POUR LE TRAITEMENT CIBLÉ DU CANCER DU PANCRÉAS
  申请人：UNIV CALIFORNIA

  公开号：WO2018044369A2

  公开（公告）日：2018-03-08

  A combination of three well-known and FDA approved compounds has been discovered to significantly suppress the proliferation of pancreatic cancer cells in clinically relevant models of pancreatic cancer. Embodiments of the invention include compositions of matter comprising a combination of agents such as metformin, simvastatin, and digoxin as well as methods of treating cancers using such agents. Illustrative methods include combining a population of pancreatic cancer cells with amounts of metformin, simvastatin, and digoxin sufficient to inhibit expression of BIRC5 protein in the population of pancreatic cancer cells, thereby inhibiting the growth of the population of pancreatic cancer cells.
• [EN] 2-CYANOPYRIMIDIN-4-YL CARBAMATE OR UREA DERIVATIVE OR SALT THEREOF, AND PHARMACEUTICAL COMPOSITION INCLUDING SAME<br/>[FR] DÉRIVÉ DE 2-CYANOPYRIMIDIN-4-YL CARBAMATE OU D'URÉE OU SEL DE CELUI-CI ET COMPOSITION PHARMACEUTIQUE LE COMPRENANT<br/>[KO] 2-시아노피리미딘-4-일 카르바메이트 혹은 유레아 유도체 또는 이의 염 및 이를 포함하는 약학 조성물
  申请人：HANLIM PHARMACEUTICAL CO LTD

  公开号：WO2019190117A1

  公开（公告）日：2019-10-03

  본 발명은 2-시아노피리미딘-4-일 카르바메이트 혹은 유레아 유도체 또는 이의 약학적으로 허용가능한 염, 이의 제조방법, 및 이를 포함하는 약학 조성물을 제공한다. 상기 2-시아노피리미딘-4-일 카르바메이트 혹은 유레아 유도체 또는 이의 약학적으로 허용가능한 염은 카뎁신 K를 선택적으로 저해함으로써 골다공증의 예방 또는 치료에 유용하게 적용될 수 있다.