卤贝他索 | 98651-66-2

• 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
• 中文名称: 卤贝他索
• 中文别名: 乌倍他索
• 英文名称: halobetasol
• 英文别名: (6a,11β,16β)-21-chloro-9,6-difluoro-11,17-dihydroxy-16-methylpregna-1,4-diene-3,20-dione；(6S,8S,9R,10S,11S,13S,14S,16S,17R)-17-(2-chloroacetyl)-6,9-difluoro-11,17-dihydroxy-10,13,16-trimethyl-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-3-one
• CAS: 98651-66-2
• 化学式: C₂₂H₂₇ClF₂O₄
• 分子量: 428.904
• InChiKey: LEHFPXVYPMWYQD-XHIJKXOTSA-N

物化性质

• 熔点：
  >218°C (dec.)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  29
• 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：
  6

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：卤贝他索尚未在母乳喂养期间进行研究。由于只有大量应用最强效的皮质类固醇才可能在母亲体内产生系统性影响，因此短期应用局部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，最好还是使用最弱效的药物，并且尽可能在最小的皮肤区域使用。特别重要的是要确保婴儿的皮肤不直接接触涂抹了药物的区域。只有低效皮质类固醇可以用于乳头或乳晕上，因为婴儿可能会直接从皮肤上摄入药物；避免在乳头上使用卤贝他索。应该使用水溶性乳膏或凝胶产品涂抹在乳房上，因为软膏可能会使婴儿通过舔舐接触到高水平的矿脂。如果局部皮质类固醇被涂抹在乳房或乳头区域，哺乳前应该彻底擦干净。 ◉ 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）涂抹在母亲的乳头上，导致她两个月大的哺乳婴儿出现QT间期延长、库欣综合症外貌、严重高血压、生长减缓和电解质异常。这位母亲从婴儿出生起就因为乳头疼痛而使用该乳膏。 ◉ 对泌乳和母乳的影响：截至修订日期，未找到相关的已发布信息。

◉ Summary of Use during Lactation:Halobetasol 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; avoid halobetasol 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. ◉ 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

• 蛋白质结合

Ulobetasol 很可能结合到血清中的皮质类固醇结合球蛋白。

Ulobetasol is likely bound to corticosteroid binding globulin in serum.

来源:DrugBank

吸收、分配和排泄

• 吸收

Ulobetasol 洗剂达到 201.1 ± 157.5 pg/mL 的 Cmax，Tmax 为 3 小时，AUC 为 1632 ± 1147 pg*h/mL。吸收可能受到皮肤完整性、使用的载体、炎症或疾病过程的影响。

Ulobetasol lotion reaches a Cmax of 201.1 ± 157.5 pg/mL, with a Tmax of 3 hours, and an AUC of 1632 ± 1147 pg\*h/mL. Absorption can be influenced by skin integrity, the vehicle used, inflammation, or disease processes.

来源:DrugBank

吸收、分配和排泄

• 消除途径

皮质类固醇主要通过尿液排出。

Corticosteroids are eliminated predominantly in the urine.

来源:DrugBank

制备方法与用途

卤倍他索（乌拉倍他索）是一种皮质类固醇，常用于研究重度局限性牛皮癣。

反应信息

• 作为产物：
  描述：

  卤贝他索丙酸酯 以 二氯甲烷 为溶剂， 生成 卤贝他索
  参考文献：
  名称：

  Crystalline forms of halobetasol propionate

  摘要：

  本发明提供了一种晶体卤倍他索丙酸酯，所述晶体卤倍他索丙酸酯从以下组中选择：具有晶体形式I的卤倍他索丙酸酯，其特征在于X射线衍射峰位置和强度如表1所述；具有晶体形式II的卤倍他索丙酸酯，其特征在于X射线衍射峰位置和强度如表2所述；具有晶体形式III的卤倍他索丙酸酯，其特征在于X射线衍射峰位置和强度如表3所述；具有晶体形式IV的卤倍他索丙酸酯，其特征在于X射线衍射峰位置和强度如表4所述；具有晶体形式V的卤倍他索丙酸酯，其特征在于X射线衍射峰位置和强度如表5所述；以及具有晶体形式VI的卤倍他索丙酸酯，其特征在于X射线衍射峰位置和强度如表6所述。

  公开号：

  US20040138191A1

文献信息

• 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] BORON-CONTAINING RHO KINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA RHO KINASE CONTENANT DU BORE
  申请人：PERCIPIAD INC

  公开号：WO2021011873A1

  公开（公告）日：2021-01-21

  The present invention provides boron-containing isoquinoline compounds as protein kinase-modulating compounds. These compounds are useful as neuroprotective and neuro-regenerative agents for the amelioration of glaucoma and other ocular neuropathies.

  本发明提供了含硼的异喹啉化合物作为蛋白激酶调节化合物。这些化合物可用作神经保护和神经再生剂，用于改善青光眼和其他眼神经病变。
• 5-Lipoxygenase-Activating Protein Inhibitor
  申请人：SCHAAB Kevin Murray

  公开号：US20090291981A1

  公开（公告）日：2009-11-26

  Described herein is the FLAP inhibitor 3-[3-tert-butylsulfanyl-1-[4-(6-ethoxy-pyridin-3-yl)-benzyl]-5-(5-methyl-pyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethyl-propionic acid, or a pharmaceutically acceptable salt thereof. Also described are methods of preparing the FLAP inhibitor, or a pharmaceutically acceptable salt thereof, including solvates, and polymorphs thereof. Also described herein are pharmaceutical compositions suitable for administration to a mammal that include the FLAP inhibitor, or a pharmaceutically acceptable salt thereof, and methods of using such pharmaceutical compositions for treating respiratory conditions or diseases, as well as other leukotriene-dependent or leukotriene mediated conditions or diseases.

  描述了一种FLAP抑制剂：3-[3-叔丁基硫基-1-[4-(6-乙氧基-吡啶-3-基)-苄基]-5-(5-甲基-吡啶-2-基甲氧基)-1H-吲哚-2-基]-2,2-二甲基丙酸，或其药用可接受盐。还描述了制备该FLAP抑制剂的方法，或其药用可接受盐，包括水合物和其多晶型。还描述了适合给予哺乳动物的药物组合物，包括FLAP抑制剂，或其药用可接受盐，以及使用此类药物组合物治疗呼吸系统疾病或疾病的方法，以及治疗其他白三烯依赖性或白三烯介导的条件或疾病的方法。
• [EN] HEMOGLOBIN MODIFIER COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS MODIFICATEURS D'HÉMOGLOBINE ET LEURS UTILISATIONS
  申请人：FRONTHERA U S PHARMACEUTICALS LLC

  公开号：WO2017218960A1

  公开（公告）日：2017-12-21

  Described herein are compounds, including pharmaceutically acceptable salts thereof, methods of making such compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat, prevent or diagnose blood-based diseases, disorders or conditions.

  本文描述了化合物，包括其药用可接受的盐，制备这些化合物的方法，包含这些化合物的药物组合物，以及使用这些化合物治疗、预防或诊断基于血液的疾病、紊乱或状况的方法。
• [EN] ESTROGEN RECEPTOR MODULATORS AND USES THEREOF<br/>[FR] MODULATEURS DE RÉCEPTEURS D'OESTROGÈNES ET LEURS UTILISATIONS
  申请人：SERAGON PHARMACEUTICALS INC

  公开号：WO2013142266A1

  公开（公告）日：2013-09-26

  Described herein are compounds that are estrogen receptor modulators. Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such estrogen receptor modulators, alone and in combination with other compounds, for treating diseases or conditions that are mediated or dependent upon estrogen receptors.

  本文描述了一些雌激素受体调节剂化合物。还描述了包括本文描述的化合物在内的药物组合物和药物，以及使用这些雌激素受体调节剂的方法，单独或与其他化合物结合，用于治疗与雌激素受体介导或依赖的疾病或症状。