莫美他松 | 105102-22-5

• 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: 莫美他松
• 中文别名: 9,21-双氯-11beta,17alpha-双羟基-16alpha-甲基孕-1,4-二烯-3,20-二酮；莫美达松；富马酸吗啉酮
• 英文名称: mometasone
• 英文别名: 9α,21-dichloro-11β,17α-dihydroxy-16α-methylpregna-1,4-diene-3,20-dione；(8S,9R,10S,11S,13S,14S,16R,17R)-9-chloro-17-(2-chloroacetyl)-11,17-dihydroxy-10,13,16-trimethyl-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-3-one
• CAS: 105102-22-5
• 化学式: C₂₂H₂₈Cl₂O₄
• 分子量: 427.368
• InChiKey: QLIIKPVHVRXHRI-CXSFZGCWSA-N

物化性质

• 熔点：
  >211oC (dec.)
• 沸点：
  586.6±50.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO（轻微）、甲醇（轻微、加热、超声处理）
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 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：
  4

ADMET

代谢

肝脏。广泛的代谢成多个代谢物。在血浆中没有检测到主要代谢物。在体外孵育时，形成的次要代谢物之一是6β-羟基-莫米他松糠酸酯。在人类肝脏微粒体中，代谢物的形成受细胞色素P-450 3A4的调控。

Hepatic. Extensive metabolism to multiple metabolites. There are no major metabolites detectable in plasma. Upon in vitro incubation, one of the minor metabolites formed is 6ß-hydroxy-mometasone furoate. In human liver microsomes, the formation of the metabolite is regulated by cytochrome P-450 3A4.

来源:DrugBank

毒理性

• 在妊娠和哺乳期间的影响

哺乳期使用总结：外用莫米松或莫米松鼻植入物在哺乳期尚未研究。由于只有大量使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，因此短期外用皮质类固醇或缓释植入物通过进入母乳对哺乳婴儿构成风险的可能性很小。然而，最谨慎的做法是使用最小面积皮肤上可能的最小效力药物。特别是要确保婴儿的皮肤不直接接触已治疗的皮肤区域。只有在婴儿可以直接从皮肤摄入药物的乳头或乳晕上使用低效皮质类固醇。应该只用水溶性乳膏或凝胶产品涂抹乳房，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应用于乳房或乳头区域，在哺乳前应彻底擦掉。 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）外用于母亲的乳头，导致其2个月大的哺乳婴儿出现QT间期延长、库欣样外观、严重高血压、生长减缓和电解质异常。这位母亲从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:Neither topical mometasone nor the mometasone nasal implant have 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 or the slow-release implant 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. 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

• 在妊娠和哺乳期间的影响

哺乳期使用总结：尚未对哺乳期间吸入的莫米松或莫米松鼻腔植入物进行研究。尽管没有进行测量，但吸入和鼻腔皮质类固醇被母体吸收进入母体血液和分泌到母乳中的量可能太小，不足以影响哺乳的婴儿。专家意见认为，在哺乳期间使用吸入和口服皮质类固醇是可以接受的。另见莫米松，外用。 ◉ 对哺乳婴儿的影响：任何皮质类固醇均无报道。 ◉ 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:Neither inhaled mometasone nor mometasone nasal implants have been studied during breastfeeding. Although not measured, the amounts of inhaled and nasal corticosteroids absorbed into the maternal bloodstream and excreted into breastmilk are probably too small to affect a breastfed infant. Expert opinion considers inhaled and oral corticosteroids acceptable to use during breastfeeding. See also Mometasone, Topical. ◉ Effects in Breastfed Infants:None reported with any corticosteroid. ◉ 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

98%到99%（在5到500 ng/mL的浓度范围内）。

98% to 99% (in a concentration range of 5 to 500 ng/mL).

来源:DrugBank

吸收、分配和排泄

• 吸收

鼻喷剂在血浆中几乎检测不到。

Nasal spray is virtually undetectable in plasma

来源:DrugBank

制备方法与用途

莫米松是一种吸入性糖皮质激素，适用于轻度哮喘患者，尤其是痰中嗜酸性粒细胞水平较低的情况。此外，莫米松在治疗慢性手部湿疹和鼻窦炎方面也显示出一定的潜力。

反应信息

• 作为反应物：
  描述：

  莫美他松 在 selenium(IV) oxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 18.0h， 以61.7%的产率得到(6R,8S,9R,10S,11S,13S,14S,16R,17R)-9-chloro-17-(2-chloroacetyl)-6,11,17-trihydroxy-10,13,16-trimethyl-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-3-one
  参考文献：
  名称：

  甾体 1,4-Dien-3-Ones 的二氧化硒氧化。一种简单方便的 6-羟基皮质类固醇途径

  摘要：

  摘要描述了一种方便的一步法，用于化学合成 6-羟基皮质类固醇，涉及二氧化硒的烯丙基氧化。

  DOI：

  10.1080/00397919108020825
• 作为产物：
  描述：

  21-氯-9-beta,11-beta-环氧-17-羟基-16-alpha-甲基孕甾-1,4-二烯-3,20-二酮 在 盐酸 作用下， 以 溶剂黄146 为溶剂， 反应 3.0h， 以83%的产率得到莫美他松
  参考文献：
  名称：

  Unusual hydroxy-?-sultone byproducts of steroid 21-methanesulfonylation. An efficient synthesis of mometasone 17-furoate (Sch 32088)

  摘要：

  An efficient two stage synthesis of the steroid anti-inflammatory agent mometasone 17-furoate (Sch 32088) 4 from 17 alpha,21-dihydroxy-16 alpha-methyl-9 beta,11 beta-oxidopregna-1,4-diene-3,20-dione 6 is described and the structures of unusual delta-hydroxy-gamma-sultone byproducts of 4-dimethylaminopyridine catalyzed methanesulfonylation of 21-hydroxy-20-ketosteroids are deduced. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(98)01146-6

文献信息

• [EN] 3,5-DIAMINO-6-CHLORO-N-(N-(4-PHENYLBUTYL)CARBAMIMIDOYL) PYRAZINE-2- CARBOXAMIDE COMPOUNDS<br/>[FR] COMPOSÉS 3,5-DIAMINO -6-CHLORO-N-(N- (4-PHÉNYLBUTYL)CARBAMIMIDOYL) PYRAZINE-2-CARBOXAMIDE
  申请人：PARION SCIENCES INC

  公开号：WO2014099673A1

  公开（公告）日：2014-06-26

  The present invention relates compounds of the formula: or pharmaceutically acceptable salts thereof, useful as sodium channel blockers, as well as compositions containing the same, processes for the preparation of the same, and therapeutic methods of use therefore in promoting hydration of mucosal surfaces and the treatment of diseases including cystic fibrosis, chronic obstructive pulmonary disease, asthma, bronchiectasis, acute and chronic bronchitis, emphysema, and pneumonia.

  本发明涉及以下化合物的公式：或其药学上可接受的盐，用作钠通道阻滞剂，以及含有这些化合物的组合物，制备这些化合物的方法，以及在促进粘膜表面水合和治疗包括囊性纤维化、慢性阻塞性肺病、哮喘、支气管扩张、急性和慢性支气管炎、肺气肿和肺炎等疾病的治疗方法。
• CHLORO-PYRAZINE CARBOXAMIDE DERIVATIVES WITH EPITHELIAL SODIUM CHANNEL BLOCKING ACTIVITY
  申请人：Parion Sciences, Inc.

  公开号：US20140171447A1

  公开（公告）日：2014-06-19

  This invention provides compounds of the formula I: and their pharmaceutically acceptable salts, useful as sodium channel blockers, compositions containing the same, therapeutic methods and uses for the same and processes for preparing the same.

  这项发明提供了式I的化合物及其药用盐，可用作钠通道阻滞剂，包含这些化合物的组合物，以及用于这些化合物的治疗方法和用途，以及制备这些化合物的方法。
• [EN] A CONJUGATE OF A CYTOTOXIC AGENT TO A CELL BINDING MOLECULE WITH BRANCHED LINKERS<br/>[FR] CONJUGUÉ D'UN AGENT CYTOTOXIQUE À UNE MOLÉCULE DE LIAISON CELLULAIRE AVEC DES LIEURS RAMIFIÉS
  申请人：HANGZHOU DAC BIOTECH CO LTD

  公开号：WO2020257998A1

  公开（公告）日：2020-12-30

  Provided is a conjugation of cytotoxic drug to a cell-binding molecule with a side-chain linker. It provides side-chain linkage methods of making a conjugate of a cytotoxic molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and immunological disorders.

  提供了一种将细胞毒性药物与一个侧链连接分子结合的共轭物。它提供了制备细胞毒性分子与细胞结合配体的共轭物的侧链连接方法，以及在靶向治疗癌症、感染和免疫性疾病中使用该共轭物的方法。
• [EN] CROSS-LINKED PYRROLOBENZODIAZEPINE DIMER (PBD) DERIVATIVE AND ITS CONJUGATES<br/>[FR] DÉRIVÉ DE DIMÈRE DE PYRROLOBENZODIAZÉPINE RÉTICULÉ (PBD) ET SES CONJUGUÉS
  申请人：HANGZHOU DAC BIOTECH CO LTD

  公开号：WO2020006722A1

  公开（公告）日：2020-01-09

  A novel cross-linked cytotoxic agents, pyrrolobenzo-diazepine dimer (PBD) derivatives, and their conjugates to a cell-binding molecule, a method for preparation of the conjugates and the therapeutic use of the conjugates.

  一种新型的交联细胞毒剂，吡咯苯并二氮杂环二聚体（PBD）衍生物，以及它们与细胞结合分子的结合物，一种制备这些结合物的方法以及这些结合物的治疗用途。
• [EN] PYRIMIDINE JAK INHIBITORS FOR THE TREATMENT OF SKIN DISEASES<br/>[FR] INHIBITEURS DE JAK À BASE DE PYRIMIDINE POUR LE TRAITEMENT DE MALADIES DE LA PEAU
  申请人：THERAVANCE BIOPHARMA R&D IP LLC

  公开号：WO2020219640A1

  公开（公告）日：2020-10-29

  The invention provides compounds of formula (I): or pharmaceutically-acceptable salts thereof, that are inhibitors of Janus kinases. The invention also provides pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat inflammatory and autoimmune skin diseases.

  该发明提供了式(I)的化合物或其药用可接受盐，这些化合物是Janus激酶的抑制剂。该发明还提供了包含这些化合物的药物组合物，以及使用这些化合物治疗炎症性和自身免疫性皮肤疾病的方法。