18-羟基皮质酮 | 561-65-9

• 物质功能分类: 有机原料 - 酮类化合物
• 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: 18-羟基皮质酮
• 中文别名: 4-孕烯-11Β,18,21-三醇-3,20-二酮；18-羟基皮质(甾)酮
• 英文名称: 11β,21-Dihydroxy-3,20-dioxo-pregn-4-en-18-ol
• 英文别名: 18-Hydroxycorticosterone；11β,18,21-trihydroxy-4-pregnene-3,20-dione；18-hydroxy corticosterone；18 hydroxycorticosterone；(8S,9S,10R,11S,13R,14S,17S)-11-hydroxy-17-(2-hydroxyacetyl)-13-(hydroxymethyl)-10-methyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one
• CAS: 561-65-9
• 化学式: C₂₁H₃₀O₅
• 分子量: 362.466
• InChiKey: HFSXHZZDNDGLQN-ZVIOFETBSA-N

物化性质

• 沸点：
  577.8±50.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)
• 闪点：
  2℃
• 溶解度：
  溶于二甲基亚砜
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  26
• 可旋转键数：
  3
• 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

ADMET

毒理性

• 毒性总结

18-羟基皮质酮是皮质酮的一种衍生物。它是通过肾上腺球状带中的酶醛甾酮合成酶在合成醛甾酮过程中的一个中间产物。（维基百科）18-羟基皮质酮（18OHB）对盐皮质激素受体的亲和力较低，主要来源于皮质酮通过醛甾酮合成酶的转化，尽管少量可能由11β-羟基酶产生。由于钠的缺乏和血管紧张素II的输注导致醛甾酮合成增加时，18OHB的血清浓度也会增加。（A15449）在特定器官中积累的18-羟基皮质酮已被证明对机体有毒害作用。

18-Hydroxycorticosterone is a derivative of corticosterone. It serves as an intermediate in the synthesis of aldosterone by the enzyme aldosterone synthase in the zona glomerulosa. (Wikipedia) 18-Hydroxycorticosterone (18OHB) has low affinity for the mineralocorticoid receptor and mainly originates from the conversion of corticosterone by the aldosterone synthase, although small amounts may be produced by the 11β-hydroxylase. Serum concentrations of 18OHB increase with increased aldosterone synthesis due to sodium depletion and angiotensin II infusion. (A15449) Accumulation of 18-hydroxycorticosterone in a given organ has been shown to be toxic for the body.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

18-羟皮质酮长期高水平与至少3种遗传性代谢错误有关，包括：肾上腺增生型5、皮质酮甲基氧化酶I缺乏和皮质酮甲基氧化酶II缺乏。

Chronically high levels of 18-hydroxycorticosterone are associated with at least 3 inborn errors of metabolism including: Adrenal hyperplasia type 5, Corticosterone methyl oxidase I deficiency and Corticosterone methyl oxidase II deficiency.

来源:Toxin and Toxin Target Database (T3DB)

安全信息

• WGK Germany：
  2

制备方法与用途

生物活性：18-羟基皮质osterone是皮质类固醇和皮质酮的衍生物，可能会引起严重的电解质失衡。

靶点： Human Endogenous Metabolite

反应信息

• 作为反应物：
  描述：

  18-羟基皮质酮 在 sodium periodate 作用下， 以 甲醇 为溶剂， 生成 反-1-(2-(4-(4-丁基环己基)苯基)乙炔基)-4-乙氧基苯
  参考文献：
  名称：

  Harnik; Kashman; Carmely, Steroids, 1986, vol. 47, # 1, p. 67 - 81

  摘要：

  DOI：
• 作为产物：
  描述：

  肾上腺酮 在 Krebs-Ringer-bicarbonate-glucose buffer 、 male CHBB-Thom rat adrenal mitochondria 、 还原型辅酶II(NADPH)四钠盐 作用下， 生成 11beta,18-环氧-18,21-二羟基孕甾-4-烯-3,20-二酮 、 18-羟基皮质酮
  参考文献：
  名称：

  Inhibition of aldosterone formation by cortisol in rat adrenal mitochondria

  摘要：

  In this work we confirm by a metabolic method the existence of at least two enzymes with 11 beta- and 18-hydroxylase activities in rat adrenal mitochondria. The method was based on the ability of cortisol (F), a foreign alternative substrate, to inhibit competitively metabolite productions from various precursors. F inhibited a) aldosterone (ALDO) production from 11-deoxycorticosterone (DOG) without affecting the yields of corticosterone (B) and 18-hydroxy-11-deoxycorticosterone (18-OHDOC); b) 18-hydroxycorticosterone and aldosterone productions from B (K-i = 2.5 +/- 0.5 mu M); and c) ALDO production from 18-OHDOC. These results suggest the existence of two categories of enzymes with both 11 beta- and 18-hydroxylase activities, one comprising those that catalyze the conversions of DOC to B and 18-OHDOC (F-insensitive reactions [FIS]) and the other one comprising the enzymes involved in the conversions of B to 18-OHB and ALDO and that of 18-OHDOC to ALDO (F-sensitive reactions [FS]). The cloned enzymes CYP11B1 and CYP11B2 would pertain respectively to the FIS and FS categories.

  DOI：

  10.1016/0039-128x(94)00064-j

文献信息

• [EN] COMPOSITIONS AND METHODS FOR TREATMENT OF PROSTATE CARCINOMA<br/>[FR] COMPOSITIONS ET MÉTHODES DE TRAITEMENT D'UN CARCINOME DE LA PROSTATE
  申请人：PELLFICURE PHARMACEUTICALS INC

  公开号：WO2016040896A1

  公开（公告）日：2016-03-17

  Disclosed herein are 1,4-naphthoquinone analogs, pharmaceutical compositions that include one or more of such 1,4-naphthoquinone analogs, and methods of treating and/or ameliorating diseases and/or conditions associated with a cancer, such as prostate cancer with such 1,4-naphthoquinone analogs. Also included are combination therapies wherein a 1,4-naphthoquinone analog disclosed herein, and a hormone therapy agent are provided to a subject suffering from a condition such as cancer.

  披露的是1,4-萘醌类似物，包括一个或多个这样的1,4-萘醌类似物的药物组合物，以及使用这些1,4-萘醌类似物治疗和/或改善与癌症相关的疾病和/或状况的方法，例如前列腺癌。还包括组合疗法，其中向患有癌症等状况的主体提供在本发明中披露的1,4-萘醌类似物和激素治疗剂。
• ALDOSTERONE SYNTHASE INHIBITORS
  申请人：BALESTRA Michael

  公开号：US20140323468A1

  公开（公告）日：2014-10-30

  The present invention relates to compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein R 1 , R 2 . R 3 , R 4 , R 5 , R 6 , R 7 , W, Y, m and n are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

  本发明涉及以下式（I）的化合物及其药学上可接受的盐，其中R1、R2、R3、R4、R5、R6、R7、W、Y、m和n如本文所定义。该发明还涉及包括这些化合物的药物组合物，使用这些化合物治疗各种疾病和紊乱的方法，制备这些化合物的方法以及在这些过程中有用的中间体。
• AFFINITY ILLUDOFULVENE CONJUGATES
  申请人：AF Chemicals, LLC,

  公开号：US20210155583A1

  公开（公告）日：2021-05-27

  In an embodiment of the invention, a composition for treating a cell population comprises a medicant. The medicant moiety can be an illudofulvene analog. In an embodiment of the invention, a composition for treating a cell population comprises an Affinity Medicant Conjugate (AMC). The affinity moiety can be an antibody, an antibody fragment, a receptor protein, a peptidic growth factor, an anti-angiogenic protein, a specific binding peptide, protease cleavable peptide, a glycopeptide, a peptide, a peptidic toxin, a protein toxin and an oligonucleotide. The affinity moiety can be covalently bound to the medicant via a linker.

  在该发明实施例中，用于治疗细胞群的组合物包括一种药物。该药物部分可以是伊卢多富烯类似物。在该发明实施例中，用于治疗细胞群的组合物包括亲和药物结合物（AMC）。亲和部分可以是抗体、抗体片段、受体蛋白、肽生长因子、抗血管生成蛋白、特异结合肽、蛋白酶可切割肽、糖肽、肽、肽毒素、蛋白毒素和寡核苷酸。亲和部分可以通过连接剂与药物共价结合。
• [EN] ALDOSTERONE SYNTHASE INHIBITORS<br/>[FR] INHIBITEURS DE L'ALDOSTÉRONE SYNTHASE
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2016089800A1

  公开（公告）日：2016-06-09

  The present invention relates to compounds of the formulas (IA) and (IB) and pharmaceutically acceptable salts thereof, wherein A and R1 - R6, are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

  本发明涉及式（IA）和（IB）的化合物及其药学上可接受的盐，其中A和R1-R6如本文所定义。该发明还涉及包含这些化合物的药物组合物，使用这些化合物治疗各种疾病和紊乱的方法，制备这些化合物的方法以及在这些过程中有用的中间体。
• Inhibitors of the Human Aldosterone Sythase CYP11B2
  申请人：Hartmann Rolf W.

  公开号：US20110112067A1

  公开（公告）日：2011-05-12

  The invention provides compounds of the general formula (I) which are inhibitors of the human aldosterone synthase, and also pharmaceutical compositions containing these compounds, and a method of treating of hyperaldosteronism and/or disorders or diseases that are mediated by 11β-hydroxylase (CYP11B1) with these compounds.

  该发明提供了一般式(I)的化合物，这些化合物是人类醛固酮合成酶的抑制剂，还包括含有这些化合物的药物组合物，以及使用这些化合物治疗高醛固酮症和/或由11β-羟化酶（CYP11B1）介导的疾病或疾病的方法。