17α-acetoxy-6-chloro-11β-hydroxy-2-oxa-4,6-pregnadiene-3,20-dione | 124530-42-3

• 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
• 英文名称: 17α-acetoxy-6-chloro-11β-hydroxy-2-oxa-4,6-pregnadiene-3,20-dione
• 英文别名: [(1R,3aS,3bS,9aR,9bS,10S,11aS)-1-acetyl-5-chloro-10-hydroxy-9a,11a-dimethyl-7-oxo-2,3,3a,3b,9,9b,10,11-octahydroindeno[4,5-h]isochromen-1-yl] acetate
• CAS: 124530-42-3
• 化学式: C₂₂H₂₇ClO₆
• 分子量: 422.906
• InChiKey: ZFZAADGQKCMMAH-AXJCLSHGSA-N

物化性质

• 沸点：
  577.3±50.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  89.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  17α-acetoxy-6-chloro-11β-hydroxy-2-oxa-4,6-pregnadiene-3,20-dione 在 chromium(VI) oxide 、 硫酸 作用下， 以 丙酮 为溶剂， 反应 0.12h， 以98.5%的产率得到17α-acetoxy-6-chloro-2-oxa-4,6-pregnadiene-3,11,20-trione
  参考文献：
  名称：

  Antiandrogen. II. Oxygenated 2-Oxapregnane Steroids.

  摘要：

  2-氧氯马地酮乙酸酯（17-乙酸氧基-6-氯-2-氧孕烯-4,6-二烯-3,20-二酮）的氧化衍生物在C11、C15和C16位点被制备为潜在的抗雄激素剂。生物评估显示，15β-羟基化合物在阉割雄性大鼠中具有很强的抗雄激素活性。

  DOI：

  10.1248/cpb.41.870
• 作为产物：
  描述：

  11β,17-diacetoxypregna-1,4,6-triene-3,20-dione 在 吡啶 、 盐酸 、 sodium hydroxide 、 sodium tetrahydroborate 、 sodium methylate 、 potassium acetate 、 sodium acetate 、 臭氧 、 sodium hydrogensulfite 、 间氯过氧苯甲酸 、 苯酚 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 、 二甲基亚砜 为溶剂， 反应 57.08h， 生成 17α-acetoxy-6-chloro-11β-hydroxy-2-oxa-4,6-pregnadiene-3,20-dione
  参考文献：
  名称：

  Antiandrogen. II. Oxygenated 2-Oxapregnane Steroids.

  摘要：

  2-氧氯马地酮乙酸酯（17-乙酸氧基-6-氯-2-氧孕烯-4,6-二烯-3,20-二酮）的氧化衍生物在C11、C15和C16位点被制备为潜在的抗雄激素剂。生物评估显示，15β-羟基化合物在阉割雄性大鼠中具有很强的抗雄激素活性。

  DOI：

  10.1248/cpb.41.870

文献信息

• Characterizations of mouse hepatic microsomal monooxygenase catalyzing 11β-hydroxylation of osaterone acetate
  作者：Kouichi Minato、Naoyuki Koizumi、Seijirou Honma、Satoshi Iwamura、Kunio Tsukamoto

  DOI：10.1016/s0006-2952(99)00098-2

  日期：1999.7

  Osaterone acetate (17 alpha-acetoxy-6-chloro-2-oxa-4,6-pregnadiene-3,20-dione,OA) is a new steroidal antiandrogen. There is a marked species difference in the metabolism of OA in that 11 beta-hydroxylated metabolites are found in the plasma, feces, and urine of mice after oral administration of OA, but there is very little metabolism in rats and humans. OA reduces the adrenal gland weight in mice, but not in rats, and this effect in mice might be explained by the species difference in 11 beta-hydroxylation activity. The objectives of this study were to elucidate the enzyme(s) involved in this particular oxidation and to explain the species difference observed. Mouse hepatic microsomes oxidize OA to 11 beta-OH OA, and this oxidation requires NADPH as a cofactor. The use of various competitive and allosteric inhibitors of cytochrome P450 and flavin-containing monooxygenase (i.e. CO, N-octylamine, and methimazole) showed that the oxidation of OA was catalyzed by cytochrome P450. In microsomes from mice pretreated with phenobarbital (a CYP2B-selective inducer), 3-methylcholanthrene (a CYP2E selective inducer), pregnenolone-16 alpha-carbonitrile (a CYP3A-selective inducer), and EtOH (a CYP2E-selective inducer), an increase in the rates of oxidation was seen only in microsomes from EtOH treated animals. However, metyrapone, a selective inhibitor for enzymes of the cytochrome P45011B and P4502B family, inhibited mouse hepatic microsomal 11 beta-hydroxylation by < 30%. The results obtained showed that the production of 11 beta-OH OA may be catalyzed by a novel cytochrome P450 in mouse liver. (C) 1999 Elsevier Science Inc.
• SIBATA, TAKEHO;YAMAKOSI, NOBUAKI;KONDZUMI, NAOYUKI;TAKEHGAVA, TOKUXIRO;TA+
  作者：SIBATA, TAKEHO、YAMAKOSI, NOBUAKI、KONDZUMI, NAOYUKI、TAKEHGAVA, TOKUXIRO、TA+

  DOI：——

  日期：——
• JPH01199993A
  申请人：——

  公开号：JPH01199993A

  公开（公告）日：1989-08-11