氯倍他索 | 25122-41-2

• 物质功能分类: 原料药 - 激素及调节内分泌功能类药 - 肾上腺皮质激素类药
• 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: 氯倍他索
• 英文名称: clobetasol
• 英文别名: tenovate；(8S,9R,10S,11S,13S,14S,16S,17R)-17-(2-chloroacetyl)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-3-one
• CAS: 25122-41-2
• 化学式: C₂₂H₂₈ClFO₄
• 分子量: 410.913
• InChiKey: FCSHDIVRCWTZOX-DVTGEIKXSA-N

物化性质

• 熔点：
  220-222°C
• 沸点：
  555.1±50.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于丙酮（少许）、DMSO（少许）、甲醇（少许）
• 物理描述：
  Solid
• 蒸汽压力：
  1.24X10-12 mm Hg at 25 °C (est)
• 碰撞截面：
  201.29 Ų [M+H]+ [CCS Type: TW]

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  5

ADMET

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用概述：克伦贝他索在母乳喂养期间尚未进行研究。由于只有最强烈的皮质类固醇的广泛使用可能会对母亲产生系统性影响，因此短期使用外用皮质类固醇不太可能通过进入母乳而对哺乳婴儿构成风险。然而，尽量使用最不强烈的药物，并尽可能在最小的皮肤面积上使用将是谨慎的做法。特别是要确保婴儿的皮肤不直接接触已经治疗过的皮肤区域。只有低效力的皮质类固醇应该用在乳头或乳晕上，因为婴儿可能会直接从皮肤上摄入药物；应避免在乳头上使用克伦贝他索。只有水溶性乳膏或凝胶产品应涂抹在乳房上，因为软膏可能会使婴儿通过舔舐接触到高水平的矿物石蜡。如果外用皮质类固醇正在涂抹在乳房或乳头区域，哺乳前应彻底擦除。 ◉ 对哺乳婴儿的影响：将具有相对较高盐皮质激素活性的皮质类固醇（异氟泼尼松醋酸酯）涂在母亲的乳头上，导致她的2个月大的哺乳婴儿出现QT间期延长、库欣综合征外观、严重高血压、生长减少和电解质异常。这位母亲从出生时起就因乳头疼痛而使用该乳膏。 一名正在哺乳（哺乳程度未说明）的新生儿母亲因天疱疮接受口服泼尼松龙25毫克/日的治疗，剂量在2周内增加至60毫克/日。她还每天服用西替利嗪10毫克，并每天两次在病变处涂抹0.1%的倍他米松。由于反应不佳，将倍他米松改为0.05%的克伦贝他索丙酸酯软膏。她在整个治疗期间继续哺乳，她的婴儿在8周龄及以后发育正常。 ◉ 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:Clobetasol has not been studied during breastfeeding. Since only extensive application of the most potent corticosteroids may cause systemic effects in the mother, it is unlikely that short-term application of topical corticosteroids would pose a risk to the breastfed infant by passage into breastmilk. However, it would be prudent to use the least potent drug on the smallest area of skin possible. It is particularly important to ensure that the infant's skin does not come into direct contact with the areas of skin that have been treated. Only the lower potency corticosteroids should be used on the nipple or areola where the infant could directly ingest the drugs from the skin; clobetasol should be avoided on the nipple. Only water-miscible cream or gel products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins via licking. Any topical corticosteroid should be wiped off thoroughly prior to nursing if it is being applied to the breast or nipple area. ◉ Effects in Breastfed Infants:Topical application of a corticosteroid with relatively high mineralocorticoid activity (isofluprednone acetate) to the mother's nipples resulted in prolonged QT interval, cushingoid appearance, severe hypertension, decreased growth and electrolyte abnormalities in her 2-month-old breastfed infant. The mother had used the cream since birth for painful nipples. A woman who was nursing (extent not stated) her newborn infant was treated for pemphigus with oral prednisolone 25 mg daily, with the dosage increased over 2 weeks to 60 mg daily. She was also taking cetirizine 10 mg daily and topical betamethasone 0.1% twice daily to the lesions. Because of a poor response, the betamethasone was changed to clobetasol propionate ointment 0.05%. She continued breastfeeding throughout treatment and her infant was developing normally at 8 weeks of age and beyond. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中和。如果患者停止呼吸，请开始人工呼吸，最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果患者呕吐，让患者向前倾或将其置于左侧（如果可能的话，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗帮助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，协助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预期癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能够吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于无意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注D5W /SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸林格氏液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。使用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。 /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

人类暴露研究/在4名志愿者（年龄20-34岁）的前臂上通过连续封闭应用丙酸氯倍他索6周诱导的皮肤萎缩后，皮肤相对快速的恢复过程被描述。

/HUMAN EXPOSURE STUDIES/ The relatively rapid cutaneous restitution following cutaneous atrophy induced on the forearms of 4 volunteers (aged 20-34 yr) by continuous occlusive application of clobetasol propionate for 6 wk is described.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在正常皮肤的大部分区域局部应用克洛贝他索丙酸酯后，只有少量药物似乎能到达真皮并随后进入系统循环，这是在通常剂量下的情况；然而，当超过常规剂量或者皮肤发炎或患病时，系统吸收可能会增加。在一项研究中，健康个体正常皮肤上在首次给药后13小时再次涂抹30克剂量的克洛贝他索丙酸酯0.05%软膏，平均血浆峰浓度在第二次给药后8小时达到0.63纳克/毫升；当使用0.05%乳膏时，平均血浆药物峰浓度略高，且在第二次给药后10小时出现。在另一项研究中，患有银屑病或湿疹的患者在单次涂抹25克剂量的0.05%软膏后约3小时，平均血浆峰浓度分别达到大约2.3或4.6纳克/毫升。

Following topical application of clobetasol propionate to most areas of normal skin, only small amounts of the drug appear to reach the dermis and subsequently the systemic circulation with the usual dosage; however, systemic absorption may be increased when the usual dosage is exceeded or when the skin is inflamed or diseased. Mean peak plasma clobetasol propionate concentrations of 0.63 ng/mL occurred in one study 8 hours after a second 30-g dose (applied 13 hours after an initial dose) of clobetasol propionate 0.05% ointment in healthy individuals with normal skin; mean peak plasma concentrations of the drug were slightly higher and occurred 10 hours after the second dose when the 0.05% cream was employed. Mean peak plasma concentrations of approximately 2.3 or 4.6 ng/mL occurred in another study about 3 hours after a single application of a 25-g dose of a 0.05% ointment in patients with psoriasis or eczema, respectively.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

克洛贝他索丙酸酯的经皮渗透性因人而异，使用不同的载体可以改变其渗透性；使用人类皮肤进行的体外研究结果表明，局部应用的克洛贝他索丙酸酯凝胶的吸收率大于局部应用的克洛贝他索丙酸酯乳膏。使用封闭敷料、以及皮肤的炎症和/或其他表皮屏障疾病（例如，银屑病、湿疹）可以增加其经皮渗透性。

Percutaneous penetration of clobetasol propionate varies among individuals and can be altered by using different vehicles; results of in vitro studies using human skin indicate that absorption of topically applied clobetasol propionate gel is greater than that of topically applied clobetasol propionate cream. Percutaneous penetration can be increased by the use of occlusive dressings and by inflammation and/or other diseases of the epidermal barrier (e.g., psoriasis, eczema).

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  T
• 安全说明：
  S36/37,S45,S53
• 危险类别码：
  R61,R48/20/21,R53,R62
• 储存条件：
  -20°C 冰箱

反应信息

• 作为产物：
  描述：

  倍他米松 在 三乙胺 、 lithium chloride 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 2.5h， 生成 氯倍他索
  参考文献：
  名称：

  抗炎药倍他米松磷酸钠制备新工艺的开发

  摘要：

  在本文中，我们报告了我们为开发一种新型和改进的抗炎类固醇活性药物成分制剂，即倍他米松磷酸钠所做的努力。从市售的倍他米松开始，合成策略包括 C21 位羟基的甲磺酸化，然后是甲磺酸酯衍生物与二叔丁基磷酸钾的关键磷酸化反应，二叔丁基磷酸酯的水解丁酯中间体在弱酸性条件下，最终成盐。开发的工艺使我们能够以 68% 的总收率在多公斤规模下获得所需的倍他米松磷酸钠 ≥ 99.9% HPLC 纯度。还讨论了工艺的成本效益、杂质分析和材料质量。

  DOI：

  10.1021/acs.oprd.2c00329

文献信息

• [EN] HETEROCYCLIC AMIDES USEFUL AS PROTEIN MODULATORS<br/>[FR] AMIDES HÉTÉROCYCLIQUES UTILES EN TANT QUE MODULATEURS DE PROTÉINE
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2017175147A1

  公开（公告）日：2017-10-12

  Disclosed are compounds having the formula (I-N), wherein q, r, s, A, B, C, RA1, RA2, RB1, RB2, RC1, RC2, R3, R4, R5, R6, R14, R15, R16, and R17, are as defined herein, or a tautomer thereof, or a salt, particularly a pharmaceutically acceptable salt, thereof.

  揭示了具有化学式（I-N）的化合物，其中q、r、s、A、B、C、RA1、RA2、RB1、RB2、RC1、RC2、R3、R4、R5、R6、R14、R15、R16和R17如本文所定义，或其互变异构体，或其盐，特别是其药用可接受盐。
• [EN] MODULATORS OF STIMULATOR OF INTERFERON GENES (STING) USEFUL IN TREATING HIV<br/>[FR] MODULATEURS DE STIMULATEUR DES GÈNES (STING) D'INTERFÉRON UTILES DANS LE TRAITEMENT DU VIH
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2019069269A1

  公开（公告）日：2019-04-11

  Disclosed are compounds having the formula: (I-N) wherein q, r, s, A, B, C, RA1, RA2, RB1, RB2, RC1, RC2, R3, R4, R5, R6, R14, R15, R16, and R17, are as defined herein, or a tautomer thereof, or a salt, particularly a pharmaceutically acceptable salt, thereof, along with combinations thereof, all of which are useful in HIV therapies.

  揭示了具有以下式的化合物：(I-N)其中q、r、s、A、B、C、RA1、RA2、RB1、RB2、RC1、RC2、R3、R4、R5、R6、R14、R15、R16和R17如本文所定义，或其互变异构体，或其盐，特别是其药用可接受盐，以及其组合物，所有这些在HIV疗法中是有用的。
• [EN] COMPOUNDS THAT INHIBIT MCL-1 PROTEIN<br/>[FR] COMPOSÉS INHIBANT LA PROTÉINE MCL-1
  申请人：AMGEN INC

  公开号：WO2018183418A1

  公开（公告）日：2018-10-04

  Provided herein are myeloid cell leukemia 1 protein (Mcl-1) inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula (I), or a stereoisomer thereof; and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.

  本文提供了髓样细胞白血病1蛋白（Mcl-1）抑制剂，其制备方法，相关的药物组合物，以及使用这些物质的方法。例如，本文提供了化合物的化学式（I）或其立体异构体；以及这些化合物的药用盐和含有这些化合物的药物组合物。本文提供的化合物和组合物可以用于治疗癌症等疾病或症状。
• COMPOUNDS THAT MODULATE INTRACELLULAR CALCIUM
  申请人：Whitten Jeffrey P.

  公开号：US20110263612A1

  公开（公告）日：2011-10-27

  Described herein are compounds and pharmaceutical compositions containing such compounds, which modulate the activity of store-operated calcium (SOC) channels. Also described herein are methods of using such SOC channel modulators, alone and in combination with other compounds, for treating diseases or conditions that would benefit from inhibition of SOC channel activity.

  本文描述了含有这些化合物的化合物和药物组合物，这些化合物调节储存操作钙（SOC）通道的活性。本文还描述了使用这种SOC通道调节剂的方法，单独或与其他化合物结合，用于治疗需要抑制SOC通道活性的疾病或症状。
• [EN] DIPEPTIDE AND TRIPEPTIDE EPOXY KETONE PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE DIPEPTIDE ET DE TRIPEPTIDE ÉPOXY CÉTONE PROTÉASES
  申请人：ONYX THERAPEUTICS INC

  公开号：WO2014152127A1

  公开（公告）日：2014-09-25

  Provided herein are dipeptide and tripeptide epoxy ketone protease inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula (X): and pharmaceutically acceptable salts and compositions including the same. The compounds and compositions provided herein may be used, for example, in the treatment of proliferative diseases including cancer and autoimmune diseases.

  本文提供了二肽和三肽环氧酮蛋白酶抑制剂，其制备方法，相关的药物组合物，以及使用它们的方法。例如，本文提供了化合物的化学式（X）：及其药用盐和包括这些化合物的组合物。本文提供的化合物和组合物可以用于治疗增生性疾病，包括癌症和自身免疫疾病。