氯可托龙 | 34097-16-0

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 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: 氯可托龙
• 中文别名: 氯可托龙戊酸酯；匹伐氯可托龙；氯可托龙特戊酸酯
• 英文名称: clocortolone pivalate
• 英文别名: clocortolone；SJ000287568；[2-[(6S,8S,9R,10S,11S,13S,14S,16R,17S)-9-chloro-6-fluoro-11-hydroxy-10,13,16-trimethyl-3-oxo-7,8,11,12,14,15,16,17-octahydro-6H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl] 2,2-dimethylpropanoate
• CAS: 34097-16-0
• 化学式: C₂₇H₃₆ClFO₅
• 分子量: 495.031
• InChiKey: SXYZQZLHAIHKKY-GSTUPEFVSA-N

物化性质

• 熔点：
  231-233°C
• 沸点：
  598.0±50.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)
• 溶解度：
  氯仿（微溶）、DMSO（微溶）、乙醇（微溶）、甲醇（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  80.7
• 氢给体数：
  1
• 氢受体数：
  6

ADMET

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：局部使用的克洛可托龙在母乳喂养期间尚未进行研究。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，因此短期使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，最谨慎的做法是使用最弱效的药物，并尽可能在最小的皮肤区域上使用。特别是要确保婴儿的皮肤不直接接触涂抹了药物的区域。应仅在水溶性乳膏或凝胶产品上涂抹乳房，因为软膏可能会使婴儿通过舔食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：将相对高矿皮质激素活性的皮质类固醇（异氟泼尼松醋酸酯）局部应用于母亲的乳头，导致她的2个月大哺乳婴儿出现QT间期延长、库欣综合征外貌、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，没有找到相关的已发布信息。

◉ Summary of Use during Lactation:Topical clocortolone 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 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)

反应信息

• 作为产物：
  描述：

  (6alpha,9beta,11beta,16alpha)-9,11-环氧-6-氟-17,21-二羟基-16-甲基-孕甾-1,4-二烯-3,20-二酮 在 盐酸 、 4-二甲氨基吡啶 、 碘代三甲硅烷 、 异丙醇 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 5.25h， 生成 氯可托龙
  参考文献：
  名称：

  [EN] PROCESS FOR THE PREPARATION OF 17-DESOXY-CORTICOSTEROIDS
  [FR] PROCÉDÉ DE PRÉPARATION DE 17-DÉSOXY-CORTICOSTÉROÏDES

  摘要：

  本发明提供了一种改进的方法，通过将17-羟基起始物与过量的碘化三甲基硅烷反应，在单一化学步骤中制备17-去氧皮质类固醇衍生物。本发明在制备具有卤素基团的17-去氧皮质类固醇衍生物方面具有明显优势，这些卤素基团位于皮质类固醇的2、6、7或9位，例如氯科尔酮或去氧美他松。

  公开号：

  WO2012011106A1

文献信息

• [EN] PYRROLOTRIAZINONE DERIVATIVES AS PI3K INHIBITORS<br/>[FR] DÉRIVÉS DE PYRROLOTRIAZINONE EN TANT QU'INHIBITEURS DES PI3K
  申请人：ALMIRALL SA

  公开号：WO2014060432A1

  公开（公告）日：2014-04-24

  New pyrrolotriazinone derivatives having the chemical structure of formula (I), are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Phosphoinositide 3-Kinases (PI3Ks)

  新的吡咯三唑酮衍生物具有化学结构式（I），公开；以及它们的制备方法，包括它们的药物组合物和它们作为磷脂酰肌醇3-激酶（PI3Ks）抑制剂在治疗中的应用。
• [EN] NOVEL TETRAHYDROTRIAZOLOPYRIMIDINE DERIVATIVES AS NHE INHIBITORS<br/>[FR] NOUVEAUX DÉRIVÉS DE TÉTRAHYDROTRIAZOLOPYRIMIDINE EN TANT QU'INHIBITEURS DE L'ÉLASTASE DE NEUTROPHILES D'ORIGINE HUMAINE
  申请人：CHIESI FARM SPA

  公开号：WO2017102674A1

  公开（公告）日：2017-06-22

  This invention relates to triazolinone derivatives having human neutrophil elastase inhibitory properties, and their use in therapy.

  这项发明涉及具有人类中性粒细胞弹性蛋白酶抑制性能的三唑酮衍生物，以及它们在治疗中的应用。
• [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] ISOTOPE ENHANCED AMBROXOL FOR LONG LASTING AUTOPHAGY INDUCTION<br/>[FR] AMBROXOL À ISOTOPE AMÉLIORÉ POUR INDUCTION D'AUTOPHAGIE DURABLE
  申请人：STC UNM

  公开号：WO2018148113A1

  公开（公告）日：2018-08-16

  The present invention is directed to 13C and/or 2H isotope enhanced ambroxol ("isotope enhanced ambroxol") and its use in the treatment of autophagy infections, especially mycobacterial and other infections, disease states and/or conditions of the lung, such as tuberculosis, especially including drug resistant and multiple drag resistant tuberculosis. Pharmaceutical compositions comprising isotope enhanced amhroxol, alone or in combination with an additional bioactive agent, especially rifamycin antibiotics, including an additional autophagy modulator (an agent which is active to promote or inhibit autophagy), thus being useful against, an autophagy mediated disease state and/or condition), especially an antophagy mediated disease state and/or condition which occurs in the lungs, for example, a Mycobacterium infection. Chronic Obstructive Pulmonary Disease (COPD), asthma, pulmonary fibrosis, cystic fibrosis, Sjogren's disease and lung cancer (small cell and non-small cell lung cancer, among other disease states and/or conditions, especially of the lung. Methods of treating autophagy disease states and/or conditions, especially including autophagy disease states or conditions which occur principally in the lungs of a patient represent a further embodiment of the present invention. An additional embodiment includes methods of synthesizing compounds according to the present invention as otherwise disclosed herein.

  本发明涉及13C和/或2H同位素增强的氨溴索（“同位素增强的氨溴索”）及其在治疗自噬感染，特别是结核分枝杆菌和其他感染、疾病状态和/或肺部疾病条件中的用途，如肺结核，特别是包括耐药和多重耐药结核病。包括同位素增强的氨溴索的药物组合物，单独或与额外的生物活性剂（特别是利福霉素类抗生素，包括额外的自噬调节剂（一种能够促进或抑制自噬的剂），因此对抗自噬介导的疾病状态和/或条件有用），特别是在肺部发生的自噬介导的疾病状态和/或条件，例如分枝杆菌感染。慢性阻塞性肺病（COPD）、哮喘、肺纤维化、囊性纤维化、干燥综合征和肺癌（小细胞和非小细胞肺癌等其他肺部疾病状态和/或条件，特别是肺部疾病状态和/或条件。治疗自噬疾病状态和/或条件的方法，特别包括治疗主要发生在患者肺部的自噬疾病状态或条件的方法，代表本发明的另一实施例。另一实施例包括根据本发明在此披露的其他方法合成化合物的方法。
• 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。