氟氢缩松 | 1524-88-5

• 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: 氟氢缩松
• 中文别名: 氟缩酮氢可松
• 英文名称: flurandrenolide
• 英文别名: fludroxycortide；flurandrenolone acetonide；(1S,2S,4R,8S,9S,11S,12S,13R,19S)-19-fluoro-11-hydroxy-8-(2-hydroxyacetyl)-6,6,9,13-tetramethyl-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icos-17-en-16-one
• CAS: 1524-88-5
• 化学式: C₂₄H₃₃FO₆
• mdl: MFCD00079290
• 分子量: 436.521
• InChiKey: POPFMWWJOGLOIF-XWCQMRHXSA-N

物化性质

• 熔点：
  247-255°
• 比旋光度：
  D +140-150° (CHCl3)
• 沸点：
  578.7±50.0 °C(Predicted)
• 密度：
  1.0796 (rough estimate)
• 溶解度：
  可溶于氯仿（少许）、乙酸乙酯（少许）、甲醇（少许）
• 物理描述：
  Solid
• 颜色/状态：
  Crystals from acetone + hexane
• 气味：
  ODORLESS
• 蒸汽压力：
  2.96X10-14 mm Hg at 25 °C (est)
• 旋光度：
  Specific optical rotation: +140-150 deg (CHCl3); max absorption: 236 nm (log e= 4.17)
• 碰撞截面：
  201.2 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  31
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.833
• 拓扑面积：
  93.1
• 氢给体数：
  2
• 氢受体数：
  7

ADMET

代谢

主要是肝脏的

Primarily hepatic

来源:DrugBank

代谢

外用皮质类固醇/主要在肝脏代谢，然后通过肾脏排泄。一些外用皮质类固醇及其代谢产物也会排入胆汁中。/外用皮质类固醇/

/Topical corticosteroids/ are metabolized primarily in the liver and then excreted in the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile. /Topical corticosteroids/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用概述：氟瑞安德诺醇在母乳喂养期间尚未进行研究。由于只有大量应用最有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，最好还是使用最不强的药物，并尽可能在最小的皮肤区域使用。特别是要确保婴儿的皮肤不直接接触涂抹了药物的区域。只有在乳头或乳晕上使用低效皮质类固醇，因为婴儿可能会直接从皮肤上摄取药物。在乳房上只能使用水溶性乳膏或凝胶产品，因为软膏可能会让婴儿通过舔舐接触到高水平的矿物石蜡。如果局部皮质类固醇应用于乳房或乳头区域，在哺乳前应彻底擦除。 ◉ 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、生长减缓和电解质异常。这位母亲从婴儿出生时起就因为乳头疼痛而使用这种乳膏。 ◉ 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:Flurandrenolide 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. 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

• 相互作用

糖皮质激素对口服抗凝治疗的影响是变化的，据报道，与糖皮质激素联合使用时，口服抗凝剂的疗效可能增强或减弱。同时接受糖皮质激素和口服抗凝剂治疗的患者应进行监测（例如，使用凝血指标），以维持所需的抗凝效果。/皮质类固醇/

The effect of glucocorticoids on oral anticoagulant therapy is variable, and the efficacy of oral anticoagulants has been reported to be enhanced or diminished with concomitant glucocorticoid administration. Patients receiving glucocorticoids and oral anticoagulants concomitantly should be monitored (e.g., using coagulation indices) in order to maintain desired anticoagulant effect. /Corticosteroids/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

因为皮质类固醇抑制抗体反应，这些药物可能会降低对类毒素和活疫苗或灭活疫苗的免疫应答。此外，皮质类固醇可能会增强活、减毒疫苗中某些微生物的复制，并且药物的超生理剂量可能会加剧对某些疫苗的神经反应。通常应推迟常规疫苗或类毒素的接种，直到皮质类固醇治疗停止。在接受免疫抑制剂量糖皮质激素治疗的患者中，接种活病毒或活、减毒疫苗，包括天花疫苗，是禁忌的。此外，如果给这类患者接种灭活疫苗，可能无法获得预期的血清抗体反应。美国公共卫生服务免疫实践咨询委员会（ACIP）和美国 Academy of Family Physicians (AAFP) 表示，在接受短期（小于2周）治疗、低到中等剂量的皮质类固醇治疗的患者中，接种活病毒疫苗通常不是禁忌的，长期交替日治疗使用短效制剂、维持生理剂量（替代疗法）或如果皮质类固醇是局部、眼科、关节内、滑囊内或肌腱内给药。如果在接受皮质类固醇治疗的患者中需要免疫接种，可能需要进行血清学测试以确保足够的抗体反应，可能需要额外的疫苗或类毒素剂量。在接受非免疫抑制剂量糖皮质激素治疗的患者或在接受糖皮质激素作为替代疗法（例如，阿狄森病）的患者中，可以进行免疫接种程序。/皮质类固醇/

Because corticosteroids inhibit antibody response, the drugs may cause a diminished response to toxoids and live or inactivated vaccines. In addition, corticosteroids may potentiate replication of some organisms contained in live, attenuated vaccines and supraphysiologic dosages of the drugs can aggravate neurologic reactions to some vaccines. Routine administration of vaccines or toxoids should generally be deferred until corticosteroid therapy is discontinued. Administration of live virus or live, attenuated vaccines, including smallpox vaccine, is contraindicated in patients receiving immunosuppressive dosages of glucocorticoids. In addition, if inactivated vaccines are administered to such patients, expected serum antibody response may not be obtained. The Public Health Service Advisory Committee on Immunization Practices (ACIP) and American Academy of Family Physicians (AAFP) state that administration of live virus vaccines usually is not contraindicated in patients receiving corticosteroid therapy as short-term (less than 2 weeks) treatment, in low to moderate dosages, as long-term alternate-day treatment with short-acting preparations, in maintenance physiologic dosages (replacement therapy), or if corticosteroids are administered topically, ophthalmically, intra-articularly, bursally, or into a tendon. If immunization is necessary in a patient receiving corticosteroid therapy, serologic testing may be needed to ensure adequate antibody response and additional doses of the vaccine or toxoid may be necessary. Immunization procedures may be undertaken in patients receiving nonimmunosuppressive doses of glucocorticoids or in patients receiving glucocorticoids as replacement therapy (e.g., Addison's disease). /Corticosteroids/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

钾耗竭利尿剂（例如，噻嗪类、呋塞米、依他尼酸）和其他耗钾药物，如两性霉素B，可能增强糖皮质激素的耗钾作用。在接受糖皮质激素和耗钾药物的患者中应密切监测血清钾水平。/皮质类固醇/

Potassium-depleting diuretics (e.g., thiazides, furosemide, ethacrynic acid) and other drugs that deplete potassium, such as amphotericin B, may enhance the potassium-wasting effect of glucocorticoids. Serum potassium should be closely monitored in patients receiving glucocorticoids and potassium-depleting drugs. /Corticosteroids/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

在使用皮质类固醇治疗期间，同时使用溃疡生成药物（如吲哚美辛）可能会增加胃肠道溃疡的风险。在使用皮质类固醇的情况下，应谨慎与阿司匹林联合使用，尤其是在低凝血酶原血症患者中。尽管同时使用水杨酸盐和皮质类固醇似乎并未增加胃肠道溃疡的发生率或严重程度，但仍应考虑这种可能性。/皮质类固醇/

Concomitant administration of ulcerogenic drugs such as indomethacin during corticosteroid therapy may increase the risk of GI ulceration. Aspirin should be used cautiously in conjunction with glucocorticoids in patients with hypoprothrombinemia. Although concomitant therapy with salicylates and corticosteroids does not appear to increase the incidence or severity of GI ulceration, the possibility of this effect should be considered. /Corticosteroids/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

• 吸收

一旦通过皮肤吸收，局部皮质类固醇会通过类似于系统性给药的皮质类固醇的药物代谢途径进行处理。

Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to those of systemically administered corticosteroids

来源:DrugBank

吸收、分配和排泄

• 消除途径

外用皮质类固醇可以从正常完整的皮肤吸收。它们主要在肝脏代谢，然后通过肾脏排出。一些外用皮质类固醇及其代谢产物也会排入胆汁中。

Topical corticosteroids can be absorbed from normal intact skin. They are metabolized primarily in the liver and then excreted in the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile.

来源:DrugBank

吸收、分配和排泄

皮质类固醇可以通过正常的完好皮肤被吸收。皮肤中的炎症和/或其他疾病过程会增加经皮吸收。... 一旦通过皮肤被吸收，外用皮质类固醇会通过类似于系统给药的皮质类固醇的药代动力学途径进行处理。皮质类固醇以不同程度与血浆蛋白结合。它们主要在肝脏代谢，然后通过肾脏排泄。一些外用皮质类固醇及其代谢物也会被排入胆汁中。/外用皮质类固醇/

Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption. ... Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees. They are metabolized primarily in the liver and then excreted in the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile. /Topical corticosteroids/

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• WGK Germany：
  3
• 海关编码：
  2937220000

制备方法与用途

治疗皮肤病的肾上腺皮质激素类药物

氟氢缩松 是一种治疗皮肤病的肾上腺皮质激素类药物，英文名为 Flurandrenolide，又称为丙酮缩氟氢羟龙、氟氢可舒松或氟缩酮氢可松。它具有抗炎作用，常用于局部皮肤疾病的治疗。市场上销售的产品通常以霜剂或软膏的形式出现，直接外用涂抹于患处。原料药为白色或类白色的粉末。

生物活性

Fludroxycortide 是一种合成的外用类固醇，同样具有抗炎作用，并有潜力用于皮肤刺激的治疗。

用途

氟氢缩松是一种中等强度的合成氟化激素，主要用于治疗皮肤过敏性疾病。其疗效主要通过抑制炎症反应、有丝分裂和合成活动来实现。适用于局部涂抹于患处，常见剂型为霜剂或软膏，浓度范围为0.0125%～0.05%。

反应信息

• 作为反应物：
  描述：

  氟氢缩松 在 氢氧化钾 、 氧气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 6α-Fluoro-16α,17α-isopropylidenedioxandrost-4-en-11β-ol-3-one-17β-carboxylic acid
  参考文献：
  名称：

  Fluorosteroids. V. Preparation and biological activity of 6α-fluoro-17β-carboxylic acids of the androstane series

  摘要：

  DOI：

  10.1007/bf00773106
• 作为产物：
  描述：

  氟尼缩松 在 Wilkinson's catalyst 、 氢气 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 65.0h， 以76%的产率得到氟氢缩松
  参考文献：
  名称：

  6α-Fluoro- 和 6α,9α-difluoro-11β,21-dihydroxy-16α,17α-propylmethylenedioxypregn-4-ene-3,20-dione：合成和评价其 C-22 差向异构体的活性和动力学

  摘要：

  摘要 人们普遍认为，糖皮质激素的抗炎作用与其在受体水平上的不良反应是分不开的。然而，通过结构改变来改变药代动力学可以为类固醇提供比目前使用的更好的治疗指数。因此，合成并研究了丁醛和 6α-氟-或 6α,9α-二氟-16α-羟基皮质醇之间的新 16α,17α-缩醛。相应的 16α,17α-二醇的缩醛化或它们的 16α,17α-丙酮化物在二恶烷中的转缩醛化产生 C-22 差向异构体的混合物，这些混合物通过制备色谱法进行拆分。或者，通过在存在惰性材料的烃中进行缩醛化和转缩醛化，使用一种有效的方法立体选择性地生产 22R-差向异构体。(22R)-6α,9α-difluoro-11β,21-dihydroxy-16α,17α-propylmethylenedioxypregn-4-ene-3,20-dione 的 C-22 构型通过单晶 X 射线衍射明确确定。本发明化合物，尤其是刚刚提到的22R-差

  DOI：

  10.1016/s0039-128x(97)00107-4

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。
• [EN] COMPOUNDS USEFUL AS CSF1 MODULATORS<br/>[FR] COMPOSÉS UTILES EN TANT QUE MODULATEURS DU FACTEUR 1 DE STIMULATION DE COLONIES
  申请人：REDX PHARMA PLC

  公开号：WO2016051193A1

  公开（公告）日：2016-04-07

  This invention relates to novel compounds and to pharmaceutical compositions comprising the novel compounds. More specifically, the invention relates to compounds useful as Colony Stimulating Factor 1 Receptor (cFMS) modulators (e.g. cFMS inhibitors). This invention also relates to processes for preparing the compounds, uses of the compounds in treatment and methods of treatment employing the compounds. Specifically, the invention relates to the use of the compounds for the treatment of cancer and autoimmune diseases.

  这项发明涉及新颖化合物以及包含这些新颖化合物的药物组合物。更具体地，该发明涉及用作集落刺激因子1受体（cFMS）调节剂（例如cFMS抑制剂）的化合物。这项发明还涉及制备这些化合物的方法，这些化合物在治疗中的用途以及利用这些化合物进行治疗的方法。具体而言，该发明涉及利用这些化合物治疗癌症和自身免疫性疾病。
• 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。