(4R)-4-[(8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid | 293738-04-2

• 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: (4R)-4-[(8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid
• CAS: 293738-04-2
• 化学式: C₂₄H₄₀O₄
• 分子量: 392.6
• InChiKey: RUDATBOHQWOJDD-GCJQIVLTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  77.8
• 氢给体数：
  3
• 氢受体数：
  4

ADMET

毒理性

• 在妊娠和哺乳期间的影响

哺乳期使用的总结：熊去氧胆酸（Ursodiol）天然存在于人乳中。由于外源性给药后母乳中熊去氧胆酸（ursodeoxycholic acid）的水平较低，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。无需特别注意事项。 对哺乳婴儿的影响：一名哺乳的婴儿（哺乳程度未说明）在母亲每天服用750至1000毫克熊去氧胆酸治疗期间，前6个月正常发育。 七位孕妇在分娩前后每天服用14毫克/公斤的熊去氧胆酸。她们报告在产后早期哺乳期间她们的婴儿没有不良反应。 一名患有原发性胆汁性肝硬化，接受口服熊去氧胆酸250毫克，每日三次的母亲，据报道正常哺乳她的婴儿，尽管哺乳的程度和持续时间没有说明。 一名患有原发性胆汁性硬化的妇女在产后3周出现严重瘙痒和血清胆酸升高。开始服用熊去氧胆酸，剂量为每天500毫克（7.5毫克/公斤），在接下来的8周内增加到每天1500毫克（25毫克/公斤）。她的哺乳婴儿（哺乳程度未说明）的心理运动发展正常，婴儿没有观察到明显的副作用。 对安卡拉土耳其一家医院的孕妇病历进行回顾性审查，发现8名患者在产后服用了13-15毫克/公斤的熊去氧胆酸。其中“大多数”患者哺乳了她们的婴儿（哺乳程度未说明）。没有报告婴儿的副作用。 一名妇女正在哺乳她8天大的早产儿，每天大约10次，每次大约15分钟。婴儿在34周妊娠时通过剖宫产出生，体重为3600克。她被诊断患有胆汁淤积，1型糖尿病和甲状腺功能减退症。她接受了熊去氧胆酸500毫克/日，胰岛素levemir和aspart，以及左甲状腺素治疗。她还服用了头孢呋辛，氟比洛芬，以及由对乙酰氨基酚、丙吡唑酮和咖啡因组成的止痛药组合。母亲总共服用了12天的熊去氧胆酸，头孢呋辛和止痛药组合服用了10天，氟比洛芬服用了15天。在熊去氧胆酸治疗期间没有注意到不良反应。 二十名哺乳母亲因胆汁淤积每天服用500至1500毫克或13至15毫克/公斤的熊去氧胆酸，具体取决于病情。熊去氧胆酸在产后3天停用。根据早期新生儿期的标准临床检查，任何新生儿都没有观察到明显的副作用，并且在常规1年随访的儿科检查中没有观察到新生儿发展的恶化。 对哺乳和乳汁的影响：截至修订日期，没有找到相关的已发布信息。

◉ Summary of Use during Lactation:Ursodiol is naturally present in human milk. Because of the low levels of ursodiol (ursodeoxycholic acid) in breastmilk after exogenous administration, amounts ingested by the infant are small and are not expected to cause any adverse effects in breastfed infants. No special precautions are required. ◉ Effects in Breastfed Infants:One breastfed (extent not stated) infant developed normally over the first 6 months of life during maternal ursodiol therapy of 750 to 1000 mg daily. Seven women who were taking ursodiol 14 mg/kg daily near term and postpartum. They reported no adverse reactions in their breastfed infants during the early postpartum period. A mother receiving oral ursodiol 250 mg 3 times daily for primary biliary cirrhosis reportedly breastfed her infant normally, although the extent and duration of breastfeeding was not stated. A woman with primary biliary cirrhosis developed severe pruritus and elevated serum bile acids 3 weeks postpartum. Ursodiol was started at a dose of 500 mg (7.5 mg/kg) daily, increasing to 1500 mg (25 mg/kg) daily over the next 8 weeks. Psychomotor development of her breastfed (extent not stated) infant was normal, and no apparent side effects were observed in the infant. A retrospective review of the medical records of pregnant patients at a hospital in Ankara, Turkey who had a diagnosis of primary biliary cirrhosis found 8 patients who took ursodiol postpartum in doses of 13–15 mg/kg daily. “Most” of the patients breastfed their infants (extent not stated). No infant side effects were reported. A woman was breastfeeding her 8-day-old preterm infant 10 times daily for about 15 minutes each time. The infant was born by cesarean section at 34 weeks of gestation with a weight of 3600 grams. She was diagnosed with cholestasis, type 1 diabetes, and hypothyroidism. She was treated with ursodiol 500 mg daily, insulin levemir and aspart, and levothyroxine. She was also taking cefuroxime, flurbiprofen, a combination of acetaminophen, propyphenazone, and caffeine. The mother took the ursodiol for a total of 12 days, cefuroxime and the analgesic combination for 10 days and flurbiprofen for 15 days. No adverse effects were noticed during the period of ursodiol treatment. Twenty nursing mothers were taking ursodiol for cholestasis in daily dosages of 500 to 1500 mg or 13 to 15 mg/kg, depending on the condition. Ursodiol was discontinued 3 days postpartum. No apparent side effects were observed in any newborn infant based on standard clinical examination during early postnatal period, and no deterioration in postnatal development was observed during routine 1-year follow-up on routine pediatric examinations. ◉ 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

• 作为产物：
  描述：

  Cholanic acid, 3,7-dihydroxy-12-oxo- 生成 (4R)-4-[(8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid
  参考文献：
  名称：

  TAKAXASI, SYUDZI;TAGUTI, ISAMU

  摘要：

  DOI：

文献信息

• Production method of steroid compound
  申请人：Takehara Jun

  公开号：US20060252948A1

  公开（公告）日：2006-11-09

  An object of the present invention is to provide a novel method for producing a steroid compound. The present invention provides a method for producing 3,7-dioxo-5β-cholanic acid or ester derivatives thereof, which uses, as raw materials, sterols having double bonds at positions 5 and 24, such as cholesta-5,7,24-trien-3β-ol, ergosta-5,7,24(28)-trien-3β-ol, desmosterol, fucosterol, or ergosta-5,24(28)-dien-3β-ol, and which comprises the following 4 steps: (I) a step of performing oxidation of a hydroxyl group at position 3 and isomerization of a double bond at position 5 to position 4; (II) a step of converting position 24 to a carboxyl group or an ester derivative thereof by the oxidative cleavage of a side chain; (III) a step of introducing an oxygen functional group into position 7; and (IV) a step of constructing a 5β-configuration by reduction of a double bond at position 4.

  本发明的目的是提供一种新型合成类固醇化合物的方法。本发明提供了一种生产3,7-二氧代-5β-胆酸或其酯衍生物的方法，该方法以具有5号和24号位置双键的甾醇为原料，例如胆甾-5,7,24-三烯-3β-醇，麦角甾-5,7,24（28）-三烯-3β-醇，去甲甾醇，褐藻甾醇或麦角甾-5,24（28）-二烯-3β-醇，并包括以下4个步骤：（I）在3号羟基位置进行氧化反应，并将5号双键异构化到4号位置；（II）通过侧链的氧化裂解将24号位置转化为羧基或其酯衍生物；（III）在7号位置引入氧功能团；（IV）通过还原4号位置的双键来构建5β-构型。
• METHOD FOR PRODUCING A STEROID COMPOUND
  申请人：Takehara Jun

  公开号：US20110009615A1

  公开（公告）日：2011-01-13

  An object of the present invention is to provide a novel method for producing a steroid compound. The present invention provides a method for producing 3,7-dioxo-5β-cholanic acid or ester derivatives thereof, which uses, as raw materials, sterols having double bonds at positions 5 and 24, such as cholesta-5,7,24-trien-3β-ol, ergosta-5,7,24(28)-trien-3β-ol, desmosterol, fucosterol, or ergosta-5,24(28)-dien-3β-ol, and which comprises the following 4 steps: (I) a step of performing oxidation of a hydroxyl group at position 3 and isomerization of a double bond at position 5 to position 4; (II) a step of converting position 24 to a carboxyl group or an ester derivative thereof by the oxidative cleavage of a side chain; (III) a step of introducing an oxygen functional group into position 7; and (IV) a step of constructing a 5β-configuration by reduction of a double bond at position 4.

  本发明的目的是提供一种新型的合成类固醇化合物的方法。本发明提供了一种生产3,7-二氧代-5β-胆酸或其酯衍生物的方法，该方法使用具有5号和24号位置上双键的类固醇作为原料，例如胆甾-5,7,24-三烯-3β-醇、麦角甾-5,7,24(28)-三烯-3β-醇、脱甾固醇、褐藻甾醇或麦角甾-5,24(28)-二烯-3β-醇，并包括以下4个步骤：(I)在3号位置进行羟基氧化和5号位置双键异构化至4号位置；(II)通过侧链的氧化裂解将24号位置转化为羧基或其酯衍生物；(III)在7号位置引入氧功能基；以及(IV)通过还原4号位置的双键来构建5β-构型。
• Verfahren zur Herstellung von Chenodeoxycholsäure und Zwischenprodukte dazu
  申请人：F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft

  公开号：EP0018515B1

  公开（公告）日：1982-10-27
• Extracts of Curcuma and Methods of Use Thereof
  申请人：Alberte Randall S.

  公开号：US20100098788A1

  公开（公告）日：2010-04-22

  The present invention relates in part to turmeric extracts that are useful for treating or preventing neurodegenerative disorders. Another aspect of the invention relates in part to turmeric extracts that are useful for treating or preventing inflammatory disorders. In some embodiments, the extracts comprise at least one compound selected from the group consisting of 25 to 500 μg bamosamine, 25 to 750 μg echinaxanthol, 100 to 3,000 μg bisdemethoxycurcumin, 50 to 500 μg daphniyunnine E and 500 to 75,000 μg curcumin per 100 mg of extract. Another aspect of the invention relates to pharmaceutical compositions comprising the aforementioned extracts. Another aspect of the invention relates to methods of treating or preventing neurodegenerative disorders comprising administering to a subject in need thereof an effective amount of the aforementioned extracts or compositions. Another aspect of the invention relates to methods of making the aforementioned extracts.
• US4460509A
  申请人：——

  公开号：US4460509A

  公开（公告）日：1984-07-17