洋地黄毒苷 | 71-63-6

• 物质功能分类: 原料药 - 循环系统用药 - 抗充血性心力衰竭药
• 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
• 中文名称: 洋地黄毒苷
• 中文别名: 洋地黄毒甙
• 英文名称: digitoxin
• 英文别名: D5878；3-[(3S,5R,8R,9S,10S,13R,14S,17R)-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-14-hydroxy-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: 71-63-6
• 化学式: C₄₁H₆₄O₁₃
• 分子量: 764.951
• InChiKey: WDJUZGPOPHTGOT-XUDUSOBPSA-N

物化性质

• 熔点：
  240 °C (dec.)(lit.)
• 比旋光度：
  D20 +4.8° (c = 1.2 in dioxane)
• 沸点：
  654.47°C (rough estimate)
• 密度：
  1.0971 (rough estimate)
• 闪点：
  9℃
• 溶解度：
  氯仿：可溶
• 物理描述：
  Digitoxin appears as odorless white or pale buff microcrystalline powder. Used as a cardiotonic drug. (EPA, 1998)
• 颜色/状态：
  Very small elongated, rectangular plates from dilute alcohol
• 气味：
  Odorless
• 味道：
  Bitter
• 蒸汽压力：
  1.09X10-27 mm Hg at 25 °C (est)
• 稳定性/保质期：
  Stable under recommended storage conditions.
• 旋光度：
  Specific optical rotation: +4.8 deg at 20 C/D (concn by volume = 1.2 g in 100 mL dioxane)
• 分解：
  When heated to decomposition it emits acrid smoke and irritating fumes.

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  54
• 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：
  183
• 氢给体数：
  5
• 氢受体数：
  13

ADMET

代谢

肝脏的。

Hepatic.

来源:DrugBank

代谢

被肝脏降解为无活性的苷元，通过逐步水解三分子地高糖将糖苷转化为苷元地高素，后者又转化为无活性的肠地高素。因为存在肠肝循环，大约25%的代谢终产物出现在粪便中。

Eliminated by hepatic degradation ...to inactive genins ...Stepwise hydrolysis of 3 molecules of digitoxose converts glycoside to aglycone digitoxigenin, which is ...converted to inactive epidigitoxigenin. Because enterohepatic recirculation occurs, approx 25% of metabolic end products appear in stool.

来源:Hazardous Substances Data Bank (HSDB)

代谢

用豚鼠的各种组织进行的研究表明，肝脏、肾脏和肾上腺组织将地高辛转化为地高辛。

Studies with various tissues of guinea pig showed that liver, kidney, and adrenal tissues converted digitoxin to digoxin.

来源:Hazardous Substances Data Bank (HSDB)

代谢

大鼠胆汁中的地高辛主要以地高辛酸葡萄糖苷和地高辛单地高糖苷的形式排出。

Digitoxin in bile of rats was excreted largely in form of glucuronide of digitoxigenin monodigitoxoside.

来源:Hazardous Substances Data Bank (HSDB)

代谢

心脏糖苷类药物会经历不同程度的肝脏代谢、肠肝循环以及肾脏过滤和重吸收，这取决于它们的极性和脂溶性。极性较低的心脏糖苷，如洋地黄毒苷，在排泄前会经历广泛的代谢。代谢过程包括逐步断裂糖分子、羟基化、对映异构化以及葡萄糖醛酸和硫酸结合物的形成。

Cardiac glycosides undergo varying degrees of hepatic metabolism, enterohepatic circulation, and renal filtration and reabsorption depending on their polarity and lipid solubility. ... Less polar glycosides such as digitoxin are metabolized extensively before they are excreted. Metabolism includes stepwise cleavage of the sugar molecules, hydroxylation, epimerization, and formation of glucuronide and sulfate conjugates. /Cardiac glycosides/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

洋地黄毒苷是一种心脏糖苷，曾用于治疗低输出充血性心力衰竭。洋地黄毒苷以足够浓度应用于眼药水或软膏以降低眼内压，倾向于引起角膜水肿和混浊。已报告一例新生儿死亡，据称是由于子宫内洋地黄毒苷过量。心脏糖苷的广泛使用以及有效治疗剂量和有毒剂量之间非常狭窄的界限导致了高毒性和相对较高的死亡率。心脏糖苷过量的表现是多种多样的体征和症状，这些症状与心脏疾病引起的影响难以区分。心脏糖苷中毒的 extracardiac 表现在急性和慢性中毒中是相似的。然而，GI 影响、中枢神经系统影响和视力障碍在急性过量后可能更为明显。急性中毒可能导致高钾血症，而慢性中毒患者可能低钾血症或正常钾血症。厌食、恶心和呕吐是毒性的早期常见症状，可能先于或紧随心脏毒性的证据。头痛、疲劳、不适、嗜睡和全身肌肉无力是心脏糖苷毒性的常见神经系统症状。头晕、眩晕、晕厥、冷漠、嗜睡、兴奋、欣快、失眠、易怒、不安、打嗝、不安、紧张、癫痫、角弓反张、昏迷和昏迷也发生了。心脏糖苷毒性剂量引起的视觉障碍可能是由对视网膜的直接影响（锥体比杆体更受影响）引起的。据报道，心脏糖苷中毒可引起暂时性视网膜神经炎，导致视力改变。心脏糖苷几乎引起了各种心律失常，同一患者可能会出现各种心律失常的组合。此外，与心脏糖苷中毒相关的心律失常可能导致充血性心力衰竭的恶化。急性中毒的原本健康个体通常表现为房室传导障碍和室上性心律失常，如窦性心动过缓。室性心律失常在这些个体中不常见；然而，当出现时，它们与严重中毒和高死亡率有关。心脏健康的儿科患者通常表现为窦性心动过缓和传导障碍；室性心律失常也发生，但不如成人常见。新生儿的中毒先兆症状可能包括窦性心动过缓、窦性心动过缓或 PR 间期延长。室上性心动过速、非阵发性房室交界性心动过速、房室分离（伴或不伴一定程度的房室传导阻滞）和阵发性房性心动过速伴变异型房室传导阻滞在成人和儿童中均常见。心脏糖苷毒性还可能引起各种房性和窦房结心律失常以及传导障碍，包括房性心动过速、心房颤动、心房扑动、房性早搏、游走性房性起搏点、窦性心动过缓、窦性心动过缓、窦性心动过缓、窦性心动过缓。心脏糖苷的过敏反应很少见，但可能会发生，通常在开始治疗后的 6-10 天内发生。皮肤反应可能是红斑、猩红热样、丘疹、水疱或大疱。皮疹通常伴有嗜酸性粒细胞增多；嗜酸性粒细胞增多也可能没有皮肤反应而发生。荨麻疹；发热；瘙痒；面部、血管性神经性或喉水肿；头皮脱发；手指甲和脚趾甲脱落；和脱屑已有报道。罕见地，据报道在给予心脏糖苷，尤其是洋地黄毒苷的过程中发生了血小板减少性紫癜。动物研究：在严重急性洋地黄毒苷中毒期间对成年和 1 周大的大鼠进行心电图监测，尽管在两个年龄组中都存在明显的神经毒性，但没有心脏毒性。所有动物均观察到高肾上腺浓度。

IDENTIFICATION AND USE: Digitoxin is a cardiac glycoside, which was used is in the treatment of low output congestive heart failure. HUMAN STUDIES: Digitoxin applied in eyedrops or ointment in sufficient concentration to reduce intraocular pressure, tends to cause corneal edema and clouding. One neonatal death has been reported, allegedly due to digitoxin overdosage in utero. The widespread use of cardiac glycosides and the very narrow margin between effective therapeutic and toxic dosages contributed to the high incidence of toxicity and the relatively high associated mortality rate. Overdosage of cardiac glycosides is manifested by a wide variety of signs and symptoms that are difficult to distinguish from effects associated with cardiac disease. The extracardiac manifestations of cardiac glycoside intoxication are similar in both acute and chronic intoxication. However, GI effects and, to a lesser extent, CNS and visual disturbances may be more pronounced following acute overdosage. Acute toxicity may cause hyperkalemia, whereas patients with chronic toxicity may be hypokalemic or normokalemic. Anorexia, nausea, and vomiting are common early signs of toxicity and may precede or follow evidence of cardiotoxicity. Headache, fatigue, malaise, drowsiness, and generalized muscle weakness are common nervous system signs of cardiac glycoside toxicity. Dizziness, vertigo, syncope, apathy, lethargy, excitement, euphoria, insomnia, irritability, agitation, hiccups, restlessness, nervousness, seizures, opisthotonos, stupor, and coma have also occurred. Visual disturbances induced by toxic doses of cardiac glycosides probably result from a direct effect on the retina (cones are affected more than rods). Transient retrobulbar neuritis has been reported to cause visual changes in cardiac glycoside intoxication. Cardiac glycosides have caused almost every kind of cardiac arrhythmia, and various combinations of arrhythmias may occur in the same patient. In addition, arrhythmias associated with cardiac glycoside intoxication may result in worsening of congestive heart failure. Otherwise healthy individuals with acute toxicity frequently present with atrioventricular conduction disturbances and supraventricular arrhythmias, such as sinus bradycardia. Ventricular arrhythmias are uncommon in these individuals; however, when present, they are associated with severe toxicity and high mortality. Pediatric patients with healthy hearts often present with sinus bradycardia and conduction disturbances; ventricular arrhythmias also occur but are less common than in adults. In neonates, premonitory signs of toxicity may include sinus bradycardia, sinoatrial arrest, or prolongation of the PR interval. Paroxysmal and nonparoxysmal atrioventricular junctional rhythms, especially nonparoxysmal atrioventricular junctional tachycardia, atrioventricular dissociation (with or without some degree of atrioventricular block), and paroxysmal atrial tachycardia with variable atrioventricular block, are common in both adults and children. Cardiac glycoside toxicity may also cause various atrial and sinoatrial nodal arrhythmias and conduction disorders including atrial tachycardia, atrial fibrillation, atria flutter, atrial premature complexes, wandering atrial pacemaker, sinus bradycardia, sinoatrial arrest, sinoatrial exit block, and sinus tachycardia. Hypersensitivity reactions to cardiac glycosides are rare but may occur, usually within 6-10 days after initiating therapy. Skin reactions may be erythematous, scarlatiniform. papular, vesicular, or bullous. Rashes are usually accompanied by eosinophilia; eosinophilia also may occur without skin reactions. Urticaria; fever; pruritus; facial, angioneurotic, or laryngeal edema; alopecia of the scalp; shedding of finger and toe nails; and desquamation have been reported. Rarely, thrombocytopenic purpura has been reported to occur during administration of cardiac glycosides, particularly digitoxin. ANIMAL STUDIES: ECG monitoring of adult and 1 week old rats during severe acute digitoxin toxicity showed lack of cardiotoxicity despite marked neurotoxicity in both age groups. High adrenal concentration noted in all animals.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

地高辛抑制Na-K-ATP酶膜泵，导致细胞内钠和钙浓度增加。细胞内钙浓度的增加可能促进收缩蛋白（例如，肌动蛋白，肌球蛋白）的激活。地高辛还作用于心脏的电活动，增加阶段4去极化的斜率，缩短动作电位持续时间，并减少最大舒张电位。

Digitoxin inhibits the Na-K-ATPase membrane pump, resulting in an increase in intracellular sodium and calcium concentrations. Increased intracellular concentrations of calcium may promote activation of contractile proteins (e.g., actin, myosin). Digitoxin also acts on the electrical activity of the heart, increasing the slope of phase 4 depolarization, shortening the action potential duration, and decreasing the maximal diastolic potential.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 相互作用

背景：心脏糖苷地高辛优先抑制乳腺癌细胞的生长，并针对Erk途径。地高辛改变介导钙代谢和IAP基因的基因表达。目的：由于最佳的治疗癌症涉及联合使用药物，我们评估了地高辛与改变钙代谢的药物组合的生长抑制效果，如thapsigargin（一种内质网/肌浆网Ca2+-ATP酶抑制剂）和statin类药物辛伐他汀，以及地高辛对凋亡的IAP途径的影响。方法：为了揭示信号通路，我们单独或与thapsigargin或辛伐他汀联合处理人类癌细胞，并使用MTT和集落形成实验测量细胞生长。我们使用组织学和Western印迹分析HEK293细胞来检测对IAPs的影响。结果：地高辛抑制了乳腺癌、结肠癌和卵巢癌细胞的生长。与对钙代谢的影响一致，地高辛与thapsigargin和辛伐他汀在ER阴性乳腺癌细胞上表现出协同作用。地高辛激活Erk途径基因的表达并抑制IAP基因的表达。对HEK293细胞的生长抑制效果不被泛胱天蛋白酶抑制剂zVAD-FMK阻断，表明地高辛可能通过一种独立于胱天蛋白酶的凋亡途径发挥作用。此外，地高辛对主要的抗凋亡蛋白XIAP蛋白没有影响。结论：地高辛似乎通过Erk和应激反应途径发挥作用，并值得研究以预防和治疗癌症。我们的发现警告心脏病患者联合使用地高辛和他汀类药物可能存在安全问题。

BACKGROUND: The cardiac glycoside digitoxin preferentially inhibits the growth of breast cancer cells and targets the Erk pathway. Digitoxin alters the expression of genes that mediate calcium metabolism and IAP genes. PURPOSE: Since the optimal treatment for cancer involves the use of agents in combination, we assessed the growth inhibitory effects of digitoxin combined with agents that alter calcium metabolism, thapsigargin, a sarcoplasmic/ER Ca(2+)-ATPase inhibitor, and the statin simvastatin, as well as digitoxin's effect on the IAP pathway of apoptosis. METHODS: To reveal signaling pathways, we treated human cancer cells with digitoxin, alone or combined with thapsigargin or simvastatin, and measured cell growth using the MTT and colony formation assays. We used histology and Western blot analysis of HEK293 cells to assay effects on IAPs. RESULTS: Digitoxin inhibited the growth of breast, colon and ovarian cancer cells. Consistent with an effect on calcium metabolism, digitoxin exhibited synergy with thapsigargin and simvastatin on ER-negative breast cancer cells. Digitoxin activates expression of Erk pathway genes and suppresses expression of IAP genes. The growth inhibitory effects on HEK293 cells are not blocked by the pancaspase inhibitor zVAD-FMK, indicating that digitoxin may act by a caspase independent pathway of apoptosis. Furthermore, digitoxin does not have an effect on XIAP protein, a major anti-apoptotic protein. CONCLUSION: Digitoxin appears to act through the Erk and stress response pathways and is worthwhile to study to prevent and treat cancer. Our findings warn of possible safety issues for cardiac patients who take a combination of digitoxin and statins.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

研究了联合药物治疗对洋地黄和毛地黄吸收、分布和消除的影响。一些药物可以通过改变胃肠道蠕动、通过物理吸附绑定药物、改变肠壁的性质或改变肠道的细菌群落来增加或减少洋地黄和毛地黄从胃肠道的吸收。如果吸收的变化足够大，洋地黄和毛地黄的稳态血清浓度可能会受到影响，可能需要调整洋地黄或毛地黄的剂量。在肝素和强心苷联合给药期间，洋地黄和毛地黄的蛋白结合减少。由于毛地黄的蛋白结合程度高于洋地黄，涉及蛋白结合变化的相互作用对毛地黄的临床意义更大。许多药物会增加或减少洋地黄和毛地黄的消除，常常导致治疗浓度不足或中毒浓度的强心苷。诱导肝微粒体酶的药物可以增加毛地黄的消除，毛地黄主要通过肝脏生物转化消除。洋地黄主要通过肾脏排泄消除；洋地黄的肾清除率可能会被血管扩张剂和甲状腺激素增加，而被奎尼丁、维拉帕米、胺碘酮和保钾利尿剂减少。由于强心苷的治疗范围较窄，因此需要对由于强心苷消除改变导致的血清浓度变化以及初步报告的强心苷与地西泮、卡托普利以及奎尼丁-戊巴比妥或奎尼丁-利福平联合治疗之间的相互作用的重要性进行进一步研究。在接受可能影响强心苷吸收、分布或消除的联合治疗的病人中，应仔细监测洋地黄中毒或治疗不足的症状。

The effects of concomitant drug therapy on the absorption, distribution, and elimination of digoxin and digitoxin are reviewed. A number of agents can increase or decrease the absorption of digoxin and digitoxin from the gastrointestinal tract by altering GI motility, binding the drugs through physical adsorption, altering the properties of the intestinal wall, or altering the bacterial flora of the intestine. The steady-state serum concentrations of digoxin and digitoxin can be affected if the changes in absorption are of sufficient magnitude, and adjustments in digoxin or digitoxin dosage may be required. A reduction in digoxin and digitoxin protein binding has occurred during concomitant administration of heparin and cardiac glycosides. Since digitoxin is more highly protein bound than digoxin, interactions that involve changes in protein binding are of much greater clinical importance with digitoxin. A number of drugs increase or decrease the elimination of digoxin and digitoxin, and subtherapeutic or toxic concentrations of the cardiac glycosides often result. Drugs that induce hepatic microsomal enzymes can increase the elimination of digitoxin, which is eliminated mainly by hepatic biotransformation. Digoxin is eliminated mainly by renal excretion; renal clearance of digoxin may be increased by vasodilators and thyroid hormones and decreased by quinidine, verapamil, amiodarone, and potassium-sparing diuretics. The clinical importance of changes in serum concentrations of the cardiac glycosides that result from alterations in glycoside elimination requires further study, as does the importance of preliminary reports of interactions between cardiac glycosides and diazepam, captopril, and combination therapy with quinidine-pentobarbital or quinidine-rifampin. Because the cardiac glycosides have a narrow therapeutic range, patients receiving concomitant therapy with agents that might affect the absorption, distribution, or elimination of the cardiac glycosides should be monitored carefully for symptoms of digitalis toxicity or undertreatment.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在已接受洋地黄治疗的患者的脉络膜-视网膜和玻璃体中，以及在一名自杀性洋地黄中毒案例中，测量了洋地黄的死后水平，并将其与股静脉血液、心肌、肾脏和肝脏中的水平进行了比较。结果根据每位患者的病史进行了解释。在自杀性中毒的个案中，脉络膜-视网膜中的洋地黄水平远高于治疗组患者。在后者的治疗组中，脉络膜-视网膜水平的变异与其他组织的变异相当。在检查左右眼脉络膜-视网膜的情况中，双眼的洋地黄水平基本相等。没有迹象表明洋地黄死后扩散到玻璃体中导致脉络膜-视网膜水平发生显著变化。根据这些结果，测定脉络膜-视网膜中的洋地黄水平有助于提高洋地黄致命中毒的死后诊断。

Postmortem digitoxin levels in the choroid-retina and vitreous humor of patients who had undergone digitoxin therapy (therapeutic group) and in one case of suicidal digitoxin poisoning were measured and compared with levels in femoral vein blood, myocardium, kidney and liver. The results were interpreted in light of the medical history of each patient. The digitoxin level in the choroid-retina of the single case of suicidal poisoning was far higher than the choroid-retinal levels in the therapeutic group. In the latter, variation in choroid-retinal levels was comparable to that in the other tissues. In cases where the choroid-retina of the right and left eyes were examined, digitoxin levels in both eyes were essentially equal. There was no indication of significant changes in choroid-retinal levels due to postmortem diffusion of digitoxin into the vitreous body. Based on these results, determination of digitoxin levels in the choroid-retina could contribute to improving postmortem diagnosis of lethal digitoxin poisoning.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在猫中...80-100分钟内，100%的洋地黄毒苷通过十二指肠给药被吸收...洋地黄苷通过血液运输...部分与白蛋白结合，部分自由存在。...组织分布主要不是心脏.../浓度最高/...在排泄器官（肝脏、胆汁、肠道、肾脏）中...。

In cats ... 100% of digitoxin is absorbed in 80-100 min following duodenal admin ... digitalis glycosides are transported by blood ... bound to ... albumin, and in part free. ... Tissue distribution is not primarily to heart ... /highest concentration/ ... in excretory organs (liver, bile, intestinal tract, kidney) ... .

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

它不能被预测地从狗的肠道吸收...。

It is not predictably absorbed from gut of dogs... .

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

...洋地黄毒苷及其代谢物的延长生物半衰期似乎取决于胆汁排泄后作为葡萄糖醛酸和硫酸盐结合物自由药物分子的再循环。

...Prolonged biological half-life of digitoxin and its metabolites appears to depend on recirculation of free drug molecules after biliary excretion as glucuronide and sulfate conjugate.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• TSCA：
  Yes
• 危险等级：
  6.1(a)
• 危险品标志：
  T
• 安全说明：
  S45
• 危险类别码：
  R23/25,R33
• WGK Germany：
  3
• 海关编码：
  2938900000
• 危险品运输编号：
  UN 2811
• RTECS号：
  IH2275000
• 包装等级：
  II
• 危险类别：
  6.1(a)
• 危险标志：
  GHS06,GHS08
• 危险性描述：
  H301,H331,H373
• 危险性防范说明：
  P261,P301 + P310,P311

制备方法与用途

生物活性

Digitoxin 是有效的 Na+/K+-ATPase 抑制剂，EC50 值为 0.78 μM。

化学性质

Digitoxin 是一种白色或类白色的结晶性粉末。熔点在 256-257℃之间，可溶于酸、氯仿、丙酮和吡啶，微溶于水及石油醚。无特殊气味，味苦。从稀醇中结晶常含有半分子或一分子结晶水或结合有一分子乙醇。真空加热至 118℃后可转化为无水物。

用途

Digitoxin 与地高辛（异羟基洋地黄毒苷）具有相同的作用，能加强心肌收缩力、减慢心率和抑制传导。其特点是作用开始缓慢而持久，适用于慢性心功能不全患者的长期服用。此药不可与酸碱类药物配伍。大鼠口服 LD50 值为 23.75 毫克/公斤；小鼠口服 LD50 值为 4.95 毫克/公斤。

生产方法

自然界中，洋地黄叶及其他强心性生药的有效成分为甾体苷。动物中的蟾蜍分泌物也含有类似物质。洋地黄毒苷分子中，糖结合在顺洋地黄毒苷配套（[143-62-4]）C3 的羟基上，苷配基带有丁烯内酯结构。

医药工业生产过程中，将洋地黄叶粉加水，在 28-35℃下发酵。用 70%乙醇提取发酵后的叶粉并浓缩、过滤。取浓缩液在 28-30℃去胶 4-6 小时后，再用氯仿提取。提取液依次用水、5%氢氧化钠溶液、水洗涤，浓缩至粘稠状，加入无水丙酮结晶，在 0-5℃放置过夜后过滤得湿品。经过柱上层析精制和提纯后得到最终产品。

分类

Digitoxin 属于有毒物质。

毒性分级

剧毒。

急性毒性

大鼠口服 LD50 值为 23.75 毫克/公斤；小鼠口服 LD50 值为 4.95 毫克/公斤。

刺激数据

狗眼睛接触 1%溶液 24 小时后呈现阳性反应。

可燃性危险特性

可燃，火场排出辛辣刺激烟雾。

储运特性

库房需低温、通风和干燥环境存放，并与食品原料分开储存。

灭火剂

水、二氧化碳、干粉、砂土。

反应信息

• 作为反应物：
  描述：

  洋地黄毒苷 在 Jones reagent 作用下， 以 丙酮 为溶剂， 反应 3.0h， 以75%的产率得到4-[(5R,10S,13R,14S,17R)-14-羟基-10,13-二甲基-3-氧代-2,4,5,6,7,8,9,11,12,15,16,17-十二氢-1H-环戊并[a]菲-17-基]-5H-呋喃-2-酮
  参考文献：
  名称：

  心脏糖苷模拟物作为潜在抗癌药的合成与评价

  摘要：

  心脏糖苷洋地黄毒毒素由连接到不稳定的三糖的类固醇核心组成，已经使用了多个世纪，用于治疗充血性心力衰竭。众所周知的药理作用是强心苷抑制Na +，K + -ATPase的能力的结果。在最近几年中，心脏糖苷还被建议具有有价值的抗癌活性。为了模拟具有稳定的碳水化合物替代物的洋地黄毒素不稳定的三糖，我们使用了不同长度的硫连接的乙二醇部分（单，二，三或四乙二醇），此外，还使用了这些接头作为合成的处理方法二价类固醇。评价制备的化合物抑制Na +，K的能力+ -ATPase及其对癌细胞MCF-7的细胞毒性作用。在抑制作用和细胞毒性作用上均观察到明显趋势，其中生物活性随大小增加而降低。最有效的Na +，K + -ATPase抑制剂是具有最短的乙二醇链（K app为0.48μM）和硫指氧还蛋白（K app为0.42μM）的化合物，两者均与洋地黄毒苷（K app为0.52μM ）相当。对于癌细胞活力测定法，发现

  DOI：

  10.1016/j.bmc.2011.02.016
• 作为产物：
  描述：

  Lanatoside A 在 biocellulase 作用下， 以 水 为溶剂， 反应 48.0h， 以68%的产率得到洋地黄毒苷
  参考文献：
  名称：

  羊毛脂苷 A 的选择性酶促转化

  摘要：

  Mesure des quantites relatives d'acetyldigitoxine et de digitoxine, obtenues par l'action de diferentes prepares enzymatiques (preparation Commerciale d'enzyme cellulolytique,酶制剂 a partir degraines de lin, d'orge et de chanvre)

  DOI：

  10.1002/ardp.19873200818

文献信息

• [EN] IMIDAZOLIUM REAGENT FOR MASS SPECTROMETRY<br/>[FR] RÉACTIF D'IMIDAZOLIUM POUR SPECTROMÉTRIE DE MASSE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2021234004A1

  公开（公告）日：2021-11-25

  The present invention relates to compounds which are suitable to be used in mass spectrometry as well as methods of mass spectrometric determination of analyte molecules using said compounds.

  本发明涉及适用于质谱的化合物，以及利用该化合物进行分析物分子的质谱测定方法。
• Substituted 1,3-thiazole compounds, their production and use
  申请人：——

  公开号：US20040053973A1

  公开（公告）日：2004-03-18

  (1) A 1,3-thiazole compound of which the 5-position is substituted with a 4-pyridyl group having a substituent including no aromatic group or (2) a 1,3-thiazole compound of which the 5-position is substituted with a pyridyl group having at the position adjacent to a nitrogen atom of the pyridyl group a substituent including no aromatic group has an excellent p38 MAP kinase inhibitory activity.

  (1) 一种1,3-噻唑化合物，其5位被取代为含有一个取代基的4-吡啶基团，该取代基不包括芳香基，或者(2) 一种1,3-噻唑化合物，其5位被取代为一个吡啶基团，该吡啶基团的氮原子邻近位置有一个取代基，该取代基不包括芳香基，具有出色的p38 MAP激酶抑制活性。
• CYCLODEXTRIN-BASED POLYMERS FOR THERAPEUTIC DELIVERY
  申请人：Cerulean Pharma Inc.

  公开号：US20130196906A1

  公开（公告）日：2013-08-01

  Provided are methods relating to the use of CDP-therapeutic agent conjugates for the treatment of a disease or disorder, e.g., autoimmune disease, inflammatory disease, central nervous system disorder, cardiovascular disease, or metabolic disorder. Also provided are CDP-therapeutic agent conjugates, particles comprising CDP-therapeutic agent conjugates, and compositions comprising CDP-therapeutic agent conjugates.

  提供了关于使用CDP-治疗剂偶联物治疗疾病或紊乱的方法，例如自身免疫疾病、炎症性疾病、中枢神经系统紊乱、心血管疾病或代谢紊乱。还提供了CDP-治疗剂偶联物、包含CDP-治疗剂偶联物的颗粒以及包含CDP-治疗剂偶联物的组合物。
• JNK INHIBITOR
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1484320A1

  公开（公告）日：2004-12-08

  A JNK inhibitor containing a compound having an isoquinolinone skeleton or a salt thereof, such as a compound represented by the formula wherein ring A and ring B are each an optionally substituted benzene ring, X is -O-, -N=, -NR3- or -CHR3-, R2 is an acyl group, an optionally esterified or thioesterified carboxyl group, an optionally substituted carbamoyl group or an optionally substituted amino group and the like, a broken line shows a single bond or a double bond, and R1 is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group and the like, and the like.

  一种含有异喹啉酮骨架或其盐的JNK抑制剂，例如由以下公式表示的化合物： 其中环A和环B分别是可选择取代的苯环，X是-O-，-N=，-NR3-或-CHR3-，R2是酰基，可选择酯化或硫酯化的羧基，可选择取代的氨基甲酰基或可选择取代的氨基等，虚线表示单键或双键，R1是氢原子，可选择取代的碳氢基团，可选择取代的杂环基团等。
• BENZAZEPINE DERIVATIVE, PROCESS FOR PRODUCING THE SAME, AND USE
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1422228A1

  公开（公告）日：2004-05-26

  The present invention provides a novel benzazepine derivative represented by formula : wherein, R1 is a 5- or 6-membered aromatic ring, R2 is lower alkyl group, etc., Y is an optionally substituted imino group, ring A and ring B are independently an optionally substituted aromatic ring, W is formula -W1-X2-W2- (W1 and W2 are independently S(O)m1 (m1 is 0, 1 or 2), etc., and X2 is an optionally substituted alkylene groupetc. ), a preparation method and use thereof.

  本发明提供了一种新型的苯并氮杂环衍生物，其由以下公式表示： 其中，R1是一个5-或6-成员的芳香环，R2是低级烷基团等，Y是可选地取代的亚氨基，环A和环B是独立地选自一个可选地取代的芳香环，W是公式-W1-X2-W2-（W1和W2是独立地为S(O)m1（m1是0、1或2）等，X2是一个可选地取代的亚烷基团等），其制备方法及其用途。