6-羟基皮质酮 | 570-25-2

• 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: 6-羟基皮质酮
• 英文名称: 6β,11β,21-trihydroxy-pregn-4-ene-3,20-dione
• 英文别名: 6β,11β,21-Trihydroxy-pregn-4-en-3,20-dion；6-Hydroxycorticosterone；(6R,8S,9S,10R,11S,13S,14S,17S)-6,11-dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one
• CAS: 570-25-2
• 化学式: C₂₁H₃₀O₅
• 分子量: 362.466
• InChiKey: BSVNAPJPBOKGSU-JJKSKHOQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  94.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  肾上腺酮 在 吡啶 、 氢氧化钾 、 高氯酸 、 air 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 为溶剂， 反应 49.5h， 生成 6-羟基皮质酮
  参考文献：
  名称：

  皮质酮、11-脱氢皮质酮和 11-脱氧皮质醇的 6α-和 6β-羟基化衍生物的合成和表征

  摘要：

  本报告描述了 6alpha,17,21- 和 6beta,17,21-trihydroxypregn-4-ene-3,20-dione、6alpha,7,21- 和 6beta,11beta,21-trihydroxypregn-4-ene-的合成3,20-dione，以及首次出现的 6alpha,21- 和 6beta,21-dihydroxypregn-4-ene-3,11,20-trione。前四种化合物分别通过 17,21-trihydroxypregn-4-ene-3,20-dione 和 11beta,21-dihydroxypregn-4-ene-3,20-dione 的 6-羟基化制备。这是通过后两种类固醇的 3-甲氧基-孕-3,5-二烯的自氧化或用 3-氯过苯甲酸氧化来实现的。6beta-羟基化类固醇的产量，但不是它们相应的6alpha-差向异构体，使用自动氧化比过酸更高。两种

  DOI：

  10.1016/0039-128x(93)90009-c

文献信息

• Isolierung und Konstitutionsermittlung weiterer Pregnanverbindungen aus Nebennieren. Über Steroide, 144. Mitteilung
  作者：R. Neher、A. Wettstein

  DOI：10.1002/hlca.19560390719

  日期：——

  Nine additional compounds of the pregnane series have been isolated from adrenals. Elucidation of their constitution showed that four are known compounds, but five are new. They are derived from the classical corticoids by hydroxylation in the 6β- or 19-positions, by reduction of the 4,5-double bond or 20-keto group, and by oxydation of the angular 18-methyl group not merely to an aldehyde, as in aldosterone

  从肾上腺中分离出了另外九种孕烷系列化合物。对它们的组成的阐明表明，四种是已知化合物，但是五种是新化合物。它们通过6β或19位羟基化，4,5-双键或20-酮基还原以及角18-甲基不仅氧化成醛而从经典皮质类固醇衍生而来，如在醛固酮中，但具有羧基。后一种衍生物具有特殊的生化意义。
• Novel steroid-activated nuclear receptors and uses therefor
  申请人：THE SALK INSTITUTE FOR BIOLOGICAL STUDIES

  公开号：EP2036925A1

  公开（公告）日：2009-03-18

  A novel nuclear receptor, termed the steroid and xenobiotic receptor (SXR), a broad-specificity sensing receptor that is a novel branch of the nuclear receptor superfamily, has been discovered. SXR forms a heterodimer with RXR that can bind to and induce transcription from response elements present in steroid-inducible cytochrome P450 genes in response to hundreds of natural and synthetic compounds with biological activity, including therapeutic steroids as well as dietary steroids and lipids. Instead of hundreds of receptors, one for each inducing compound, the invention SXR receptors monitor aggregate levels of inducers to trigger production of metabolizing enzymes in a coordinated metabolic pathway. Agonists and antagonists of SXR are administered to subjects to achieve a variety of therapeutic goals dependent upon modulating metabolism of one or more endogenous steroids or xenobiotics to establish homeostasis. An assay is provided for identifying steroid drugs that are likely to cause drug interaction if administered to a subject in therapeutic amounts. Transgenic animals are als provided which express human SXR, thereby serving as useful models for human response to various agents which poterltially impact P450-dependent metabolic processes.

  人们发现了一种新型核受体，称为类固醇和异生物受体（SXR），它是一种广特异性感应受体，是核受体超家族的一个新分支。SXR 与 RXR 形成异源二聚体，能与类固醇诱导的细胞色素 P450 基因中的反应元件结合并诱导其转录，从而对数百种具有生物活性的天然和合成化合物（包括治疗性类固醇以及膳食类固醇和脂质）做出反应。本发明的 SXR 受体不需要数百种受体（每种诱导化合物一种受体），而是监测诱导剂的总体水平，从而在协调的代谢途径中触发代谢酶的产生。对受试者施用 SXR 的激动剂和拮抗剂，以实现各种治疗目标，这些目标取决于调节一种或多种内源性类固醇或异生物的代谢，从而建立体内平衡。本研究提供了一种检测方法，可用于识别以治疗量给受试者用药时可能引起药物相互作用的类固醇药物。此外，还提供了表达人类 SXR 的转基因动物，从而作为人类对可能影响 P450 依赖性代谢过程的各种药物反应的有用模型。
• Xenobiotic compound modulated expression systems and uses therefor
  申请人：——

  公开号：US20030104519A1

  公开（公告）日：2003-06-05

  A novel nuclear receptor, termed the steroid and xenobiotic receptor (SXR), a broad-specificity sensing receptor that is a novel branch of the nuclear receptor superfamily, has been discovered. SXR forms a heterodimer with RXR that can bind to and induce transcription from response elements present in steroid-inducible cytochrome P450 genes in response to hundreds of natural and synthetic compounds with biological activity, including therapeutic steroids as well as dietary steroids and lipids. Instead of hundreds of receptors, one for each inducing compound, the invention SXR receptors monitor aggregate levels of inducers to trigger production of metabolizing enzymes in a coordinated metabolic pathway. Agonists and antagonists of SXR are administered to subjects to achieve a variety of therapeutic goals dependent upon modulating metabolism of one or more endogenous steroids or xenobiotics to establish homeostasis. An assay is provided for identifying steroid drugs that are likely to cause drug interaction if administered to a subject in therapeutic amounts. Transgenic animals are also provided which express human SXR, thereby serving as useful models for human response to various agents which potentially impact P450-dependent metabolic processes. Also provided are expression systems and expression vectors having SXR receptors and the like operably linked to target genes of interest.

  人们发现了一种新型核受体，称为类固醇和异生物受体（SXR），它是一种广特异性感应受体，是核受体超家族的一个新分支。SXR 与 RXR 形成异源二聚体，能与类固醇诱导的细胞色素 P450 基因中的反应元件结合并诱导其转录，从而对数百种具有生物活性的天然和合成化合物（包括治疗性类固醇以及膳食类固醇和脂质）做出反应。本发明的 SXR 受体不需要数百种受体（每种诱导化合物一种受体），而是监测诱导剂的总体水平，从而在协调的代谢途径中触发代谢酶的产生。对受试者施用 SXR 的激动剂和拮抗剂，以实现各种治疗目标，这些目标取决于调节一种或多种内源性类固醇或异生物的代谢，从而建立体内平衡。本研究还提供了一种检测方法，用于确定以治疗量给受试者用药时可能引起药物相互作用的类固醇药物。还提供了表达人类 SXR 的转基因动物，从而作为人类对可能影响 P450 依赖性代谢过程的各种制剂的反应的有用模型。此外，还提供了表达系统和表达载体，这些系统和载体具有可与感兴趣的靶基因连接的 SXR 受体等。
• Modulation of metabolism of steroids and xenobiotics
  申请人：——

  公开号：US20040254135A1

  公开（公告）日：2004-12-16

  In accordance with the present invention, there are provided methods for modulating Phase II conjugating enzymes such as, for example, UGTs. Phase II conjugating enzymes such as UGTs function in concert with Phase I monooxygenase enzymes such as cytochrome P450 enzymes (CYPs) to eliminate steroids and xenobiotics. Nuclear receptors SXR/PXR and CAR are xenosensors regulating expression of CYP genes such as CYP3A and 2B. The ability of this group of receptors to regulate expression of UGT in response to steroids and/or xenobiotics provides novel approaches for direct regulation/activation of a glucuronidation pathway, thereby providing methods to achieve physiologic homeostasis with respect to steroids and/or xenobiotics. SXR/PXR and CAR regulation/activation of UGT represents the first evidence of receptors that can transduce/transactivate both Phase I and Phase II adaptive hepatic response. In another aspect, the present invention also provides transgenic rodents expressing one or more of SXR, CAR or PXR.

  根据本发明，提供了调节第二阶段结合酶（如 UGTs）的方法。第二阶段共轭酶如 UGTs 与第一阶段单氧化酶如细胞色素 P450 酶（CYPs）协同作用，消除类固醇和异种生物。核受体 SXR/PXR 和 CAR 是调节 CYP 基因（如 CYP3A 和 2B）表达的异种感应器。这组受体能够在类固醇和/或异生物的作用下调节 UGT 的表达，为直接调节/激活葡萄糖醛酸化途径提供了新的方法，从而为实现类固醇和/或异生物的生理平衡提供了方法。SXR/PXR 和 CAR 对 UGT 的调节/激活首次证明了受体可以转导/转活第一阶段和第二阶段的适应性肝脏反应。另一方面，本发明还提供了表达一种或多种 SXR、CAR 或 PXR 的转基因啮齿动物。
• Dusza et al., Journal of Organic Chemistry, 1962, vol. 27, p. 4046,4048
  作者：Dusza et al.

  DOI：——

  日期：——