9-氯-11beta,17,21-三羟基-16beta-甲基孕甾-1,4-二烯-3,20-二酮 21-丙酸酯 | 69224-79-9

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物 - 羧酸酯及其衍生物的盐
• 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: 9-氯-11beta,17,21-三羟基-16beta-甲基孕甾-1,4-二烯-3,20-二酮 21-丙酸酯
• 中文别名: 9-氯-11beta,17,21-三羟基-16beta-甲基孕甾-1,4-二烯-3,20-二酮21-丙酸酯
• 英文名称: 21-beclomethasone monopropionate
• 英文别名: beclomethasone 21-monopropionate；beclomethasone-21-propionate；[2-[(8S,9R,10S,11S,13S,14S,16S,17R)-9-chloro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl]-2-oxoethyl] propanoate
• CAS: 69224-79-9
• 化学式: C₂₅H₃₃ClO₆
• 分子量: 464.986
• InChiKey: OPNPEZLXXKGRTA-XGQKBEPLSA-N

物化性质

• 熔点：
  139-141°C
• 沸点：
  618.2±55.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)
• 溶解度：
  二恶烷（轻微）、DMSO（轻微）、甲醇（轻微）

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  9Alpha-氯-16Β-甲基孕甾-1,4-二烯-11Β,17Alpha,21-三醇-3,20-二酮-17-丙酸酯 以 various solvent(s) 为溶剂， 反应 18.0h， 生成 9-氯-11beta,17,21-三羟基-16beta-甲基孕甾-1,4-二烯-3,20-二酮 21-丙酸酯
  参考文献：
  名称：

  Differential Potency of Beclomethasone Esters In-vitro on Human T-lymphocyte Cytokine Production and Osteoblast Activity

  摘要：

  倍氯米松二丙酸酯是一种吸入型皮质类固醇，用于治疗哮喘。它代谢生成17-倍氯米松单丙酸酯，该化合物与皮质类固醇受体的亲和力比母化合物更强，并生成倍氯米松。我们研究了倍氯米松二丙酸酯、17-倍氯米松单丙酸酯和倍氯米松（与地塞米松作为参考类固醇进行比较）在两种不同的人类细胞类型中的效力，即外周血单个核细胞和成骨细胞。

  我们发现，倍氯米松二丙酸酯、17-倍氯米松单丙酸酯（EC50为10^-14m）和倍氯米松（EC50约为10^-12m）在抑制外周血单个核细胞产生白细胞介素-5方面比地塞米松（EC50为10^-8m）更有效。相反，在影响成骨细胞的几种功能检测（如碱性磷酸酶活性和骨钙素合成）方面，倍氯米松二丙酸酯、17-倍氯米松单丙酸酯和倍氯米松与地塞米松的效力相当（EC50范围为0.3-1.2倍的10^-9m）。

  这些结果表明，皮质类固醇的相对生物活性在不同的人类细胞类型之间存在差异，并且在受体结合测定中观察到的亲和力并不一定能够预测在细胞群体中的生物活性，例如外周血单个核细胞和成骨细胞，这些细胞群体被认为与疗效和副作用有关。

  DOI：

  10.1211/0022357001774174

文献信息

• EUTECTIC SOLVENTS COMPRISING PHARMACEUTICAL AGENTS, AND METHODS OF MAKING AND USE THEREOF
  申请人：Novilla Pharmaceuticals, Inc.

  公开号：US20210308048A1

  公开（公告）日：2021-10-07

  The present invention generally relates to eutectic compositions comprising pharmaceutical agents and other beneficial substances, and in particular, to eutectic compositions where the pharmaceutical agent and beneficial substance forms a part of the eutectic composition. In one aspect, the pharmaceutical agent and beneficial substance defines part of the eutectic composition, i.e., rather than just being present within the eutectic composition. In one set of embodiments, at least about 20 mol % of the eutectic composition may comprise a hydrogen bond donor and a hydrogen bond acceptor, for example, acetaminophen and choline chloride, respectively. However, in other embodiments, the pharmaceutical agent can be either donor or acceptor, and the other agent either donor or acceptor. Other aspects are generally directed to methods of making such compositions, methods of using such compositions, kits including such compositions, etc.
• Differential Potency of Beclomethasone Esters In-vitro on Human T-lymphocyte Cytokine Production and Osteoblast Activity
  作者：Celina Seeto、Heeja Namkung-Matthai、Shalini Jayram、Kuncoro Foe、Ken F Brown、J Margaret Hughes、Rebecca S Mason、Carol L Armour、J Paul Seale

  DOI：10.1211/0022357001774174

  日期：2010.2.18

  Beclomethasone dipropionate is an inhaled corticosteroid, used for the treatment of asthma. It is metabolised to 17-beclomethasone monopropionate, which has greater affinity for corticosteroid receptors than the parent compound, and to beclomethasone. We investigated the potency of beclomethasone dipropionate, 17-beclomethasone monopropionate and beclomethasone (compared with dexamethasone as a reference steroid) in two different human cell types, peripheral blood mononuclear cells and osteoblasts.

  We found that beclomethasone dipropionate, 17-beclomethasone monopropionate (EC50 10−14  m) and beclomethasone (EC50 approx. 10−12  m) were much more potent than dexamethasone (EC50 10−8  m) in inhibiting interleukin-5 production by peripheral blood mononuclear cells. In contrast, beclomethasone dipropionate, 17-beclomethasone monopropionate and beclomethasone were equipotent with dexamethasone (EC50 range 0.3–1.2 times 10−9  m) in affecting several functional assays of osteoblasts (e.g. alkaline phosphatase activity and osteocalcin synthesis).

  These results show that the relative bioactivities of corticosteroids vary between different human cell types, and that affinities observed in receptor binding assays are not necessarily predictive of the bioactivity in cell populations, such as peripheral blood mononuclear cells and osteoblasts, which are putatively relevant to efficacy and side effects respectively.

  倍氯米松二丙酸酯是一种吸入型皮质类固醇，用于治疗哮喘。它代谢生成17-倍氯米松单丙酸酯，该化合物与皮质类固醇受体的亲和力比母化合物更强，并生成倍氯米松。我们研究了倍氯米松二丙酸酯、17-倍氯米松单丙酸酯和倍氯米松（与地塞米松作为参考类固醇进行比较）在两种不同的人类细胞类型中的效力，即外周血单个核细胞和成骨细胞。

  我们发现，倍氯米松二丙酸酯、17-倍氯米松单丙酸酯（EC50为10^-14m）和倍氯米松（EC50约为10^-12m）在抑制外周血单个核细胞产生白细胞介素-5方面比地塞米松（EC50为10^-8m）更有效。相反，在影响成骨细胞的几种功能检测（如碱性磷酸酶活性和骨钙素合成）方面，倍氯米松二丙酸酯、17-倍氯米松单丙酸酯和倍氯米松与地塞米松的效力相当（EC50范围为0.3-1.2倍的10^-9m）。

  这些结果表明，皮质类固醇的相对生物活性在不同的人类细胞类型之间存在差异，并且在受体结合测定中观察到的亲和力并不一定能够预测在细胞群体中的生物活性，例如外周血单个核细胞和成骨细胞，这些细胞群体被认为与疗效和副作用有关。