10,13-二甲基-17-氧代-3-磺基氧基-1,2,3,4,7,8,9,11,12,14,15,16-十二氢环戊烯并[a]菲 | 651-48-9

• 物质功能分类: 生物化工 - 生物反应调节剂
• 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: 10,13-二甲基-17-氧代-3-磺基氧基-1,2,3,4,7,8,9,11,12,14,15,16-十二氢环戊烯并[a]菲
• 中文别名: 硫酸脱氢表雄酮；硫酸普拉睾酮
• 英文名称: dehydroepiandrosterone sulfate
• 英文别名: [(3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-oxo-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-yl] hydrogen sulfate
• CAS: 651-48-9
• 化学式: C₁₉H₂₈O₅S
• 分子量: 368.494
• InChiKey: CZWCKYRVOZZJNM-USOAJAOKSA-N

物化性质

• 沸点：
  468.81°C (rough estimate)
• 密度：
  1.1763 (rough estimate)
• 熔点：
  190-192 °C
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  89
• 氢给体数：
  1
• 氢受体数：
  5

ADMET

代谢

硫酸脱氢表雄酮（DHEAS）是DHEA的硫酸酯。这种转化主要由肾上腺、肝脏和小肠中的磺基转移酶（SULT2A1）可逆催化。脱氢表雄酮硫酸盐也可以通过类固醇硫酸酯酶的作用逆向转化为DHEA。在血液中，大部分的DHEA以DHEAS的形式存在，其水平大约是自由态DHEA的300倍。口服摄入的DHEA在通过肠道和肝脏时会转化为其硫酸盐。DHEAS水平没有昼夜变化。在男性和女性中，将DHEAS转化为DHEA，然后再转化为睾酮需要17β-羟基类固醇脱氢酶。

Dehydroepiandrosterone sulfate (DHEAS) is the sulfate ester of DHEA. This conversion is reversibly catalyzed by sulfotransferase (SULT2A1) primarily in the adrenals, the liver, and small intestine. DHEA sulfate can also be back-converted to DHEA through the action of steroid sulfatase. In the blood, most DHEA is found as DHEAS with levels that are about 300 times higher than those of free DHEA. Orally ingested DHEA is converted to its sulfate when passing through intestines and liver. DHEAS levels show no diurnal variation. In males and females, conversion of DHEAS to DHEA and then to testosterone requires the enzyme 17β-hydroxysteroid dehydrogenase.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

尽管它主要作为更强大雄激素（如睾酮和二氢睾酮）的内源性前体发挥作用，但脱氢表雄酮（DHEA，由脱氢表雄酮硫酸盐DHEAS产生）已被发现自身具有一定程度雄激素活性，作为雄激素受体低亲和力（Ki = 1 μM）、弱的部分激动剂。脱氢表雄酮还已被发现能与雌激素受体ERα和ERβ结合并激活，其Ki值分别为1.1 μM和0.5 μM。当摄入足够量时，脱氢表雄酮硫酸盐可以引起男性化效应。脱氢表雄酮硫酸盐被认为是一种雄激素类固醇前体，因为其产物睾酮是一种雄激素或男性激素。在男性和女性中，将脱氢表雄酮硫酸盐转化为睾酮需要17β-羟基类固醇脱氢酶。睾酮在男性生殖组织（如睾丸和前列腺）的发育以及促进次级性征（如肌肉增加、骨质量和体毛生长）中发挥关键作用。睾酮水平过高可能导致女性男性化或年轻男孩早熟。成年人中长期高水平的睾酮会增加心脏病、中风和血栓的风险，因为它会降低高密度脂蛋白（好胆固醇）的水平。男性乳腺组织的发育，即男性乳腺发育症（通常由循环中的雌二醇水平过高引起），是因为睾酮通过芳香酶酶转化为雌二醇的增加。男性还可能出现性功能减退和暂时性不育。

Although it predominantly functions as an endogenous precursor to more potent androgens such as testosterone and dihydroxytestosterone, DHEA (which is produced from DHEAS) has been found to possess some degree of androgenic activity in its own right, acting as a low affinity (Ki = 1 μM), weak partial agonist of the androgen receptor. DHEA has also been found to bind to and activate the ERα and ERβ estrogen receptors with Ki values of 1.1 μM and 0.5 μM, respectively. When taken in sufficient quantities DHEAS can cause masculinizing effects. DHEAS is considered an androgenic steroid precursor because testosterone (its product) is an androgen or male hormone. In males and females, conversion of DHEAS to testosterone requires the enzyme 17β-hydroxysteroid dehydrogenase. Testosterone plays a key role in the development of male reproductive tissues such as the testis and prostate as well as promoting secondary sexual characteristics such as increased muscle, bone mass, and the growth of body hair. High levels of testosterone can lead to masculinization in females or premature puberty in young boys. Chronically high levels in adults increase the incidence of heart attack, stroke and blood clots by lowering the level of HDL (good cholesterol). The development of breast tissue in males, a condition called gynecomastia (which is usually caused by high levels of circulating estradiol), arises because of increased conversion of testosterone to estradiol by the enzyme aromatase. Reduced sexual function and temporary infertility can also occur in males.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类无致癌性（未列入国际癌症研究机构IARC清单）。

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

一些研究人员认为，脱氢表雄酮硫酸盐（DHEAS）补充剂实际上可能会增加乳腺癌、前列腺癌、心脏病、糖尿病和中风的风险。DHEAS可能会刺激对激素敏感的癌症类型的肿瘤生长，例如某些类型的乳腺癌、子宫癌和前列腺癌。DHEAS可能会增加患有良性前列腺增生（BPH），即前列腺肿大的男性的前列腺肿胀。高剂量的DHEAS可能会导致攻击性、易怒、睡眠困难和女性身体或面部毛发的生长。它还可能停止月经并降低高密度脂蛋白（'好'胆固醇）的水平，这可能会增加心脏病的风险。其他报告的副作用包括痤疮、心脏节律问题、肝脏问题、脱发（从头皮）和油性皮肤。在女性中，脱氢表雄酮（DHEA）可能会导致乳房大小减小、声音变低、生殖器大小增加、月经不规律、皮肤油腻和不自然的毛发生长。在男性中，DHEAS可能会导致攻击性、乳房触痛或增大、睾丸大小减小和尿急。DHEAS可能会干扰身体使用肝脏细胞色素P450酶系统处理某些物质的方式。长期高水平的脱氢表雄酮硫酸盐与男性假两性畸形伴乳房发育有关。

Some researchers believe DHEAS supplements might actually raise the risk of breast cancer, prostate cancer, heart disease, diabetes and stroke. DHEAS may stimulate tumor growth in types of cancer that are sensitive to hormones, such as some types of breast, uterine, and prostate cancer. DHEAS may increase prostate swelling in men with benign prostatic hyperplasia (BPH), an enlarged prostate gland. High doses of DHEAS may cause aggressiveness, irritability, trouble sleeping, and the growth of body or facial hair on women. It also may stop menstruation and lower the levels of HDL ('good' cholesterol), which could raise the risk of heart disease. Other reported side effects include acne, heart rhythm problems, liver problems, hair loss (from the scalp), and oily skin. In women, DHEA may cause decreased breast size, a deep voice, increased genital size, irregular periods, oily skin, and unnatural hair growth. In men, DHEAS may cause aggression, breast tenderness or enlargement, decreased testes size, and urinary urgency. DHEAS may interfere with the way the body processes certain agents using the liver's cytochrome P450 enzyme system. Chronically high levels of Dehydroepiandrosterone sulfate are associated with male pseudohermaphrodism with gynecomastia.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

内源性的，摄取

Endogenous, ingestion

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

在女性中，脱氢表雄酮（DHEAS）可能导致乳房变小、声音变低、生殖器增大、月经不规律、皮肤油性增加和不自然的毛发生长。在男性中，脱氢表雄酮（DHEAS）可能导致攻击性、乳房触痛或增大、睾丸体积减小和尿急。

In women, DHEAS may cause decreased breast size, a deep voice, increased genital size, irregular periods, oily skin, and unnatural hair growth. In men, DHEAS may cause aggression, breast tenderness or enlargement, decreased testes size, and urinary urgency.

来源:Toxin and Toxin Target Database (T3DB)

制备方法与用途

概述

DHEA（去氢表雄酮、脱氢表雄甾酮）是血液中含量最高的类固醇激素。其化学名称为3β-羟基雄甾-5-烯-17-酮，是一种具有胆固醇△5,6-双键及可酯化3β-羟基的甾体，吸收波长范围为200~215nm。DHEA主要以DHEA硫酸酯（DHEAS）的形式进入血液循环中，后者在血浆中的浓度是前者的300~500倍。DHEA与DHEAS通过磺基转移酶相互转换，保持相对稳定的浓度，但只有DHEA具有生物活性。

药物应用

血液中DHEA水平与老年疾病密切相关。肾上腺囊肿、肿瘤等肾上腺疾病会增加DHEA的浓度；而年龄增长和绝经等因素则会导致DHEA浓度下降。低DHEA浓度增加了老年人患高血压病、阿尔茨海默病等疾病的风险。因此，监测血浆中DHEA（S）的浓度对于预防和诊治老年人相关疾病具有重要意义。

反应信息

• 作为反应物：
  描述：

  10,13-二甲基-17-氧代-3-磺基氧基-1,2,3,4,7,8,9,11,12,14,15,16-十二氢环戊烯并[a]菲 在 glucuronidase 、 sulphatase from Patella vulgata 咪唑 、 potassium acetate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 (3S)-3-tert-butyldimethylsilyloxyandrost-5-en-17-one
  参考文献：
  名称：

  Identification and quantification of dehydroepiandrosterone sulphate in saliva

  摘要：

  3 beta-Hydroxy-5-androsten-17-one (dehydroepiandrosterone) sulphate has been separated from an extract of human saliva by ion exchange gel chromatography and identified by high resolution gas chromatography-high resolution mass spectrometry of the tert-butyldimethylsilyl derivative of the neutral steroid obtained by enzymic hydrolysis. Quantitative analyses, employing 7,7-2H-dehydroepiandrosterone sulphate as the internal standard, have indicated concentrations in the saliva of young adult subjects to be generally in the range 0.9-5.7 nmol/l, though concentrations as high as 10.7 nmol/l have been observed.

  DOI：

  10.1016/0039-128x(82)90126-x
• 作为产物：
  描述：

  去氢表雄酮 在 tyrosine-ester sulfotransferase 6-氨基-9-[3-羟基-5-[(羟基-磺基氧基-磷酰)氧基甲基]-4-膦酰氧基-四氢呋喃-2-基]-嘌呤 作用下， 以 acetate buffer 为溶剂， 反应 0.08h， 生成 10,13-二甲基-17-氧代-3-磺基氧基-1,2,3,4,7,8,9,11,12,14,15,16-十二氢环戊烯并[a]菲
  参考文献：
  名称：

  小鼠类固醇磺基转移酶：底物特异性和初步X射线晶体学分析。

  摘要：

  为了研究其对天然和合成类固醇激素的底物特异性，在大肠杆菌细胞中表达了三种小鼠胞质磺基转移酶。Km和Vmax值分别证实了雌激素和羟类固醇磺基转移酶对雌二醇和脱氢表雄酮的底物特异性较高。与之形成鲜明对比的是，合成的雌激素二乙基己烯雌酚被两种酶有效地代谢成其二硫酸酯。这些磺基转移酶显示出仅对二乙基间苯三酚的反式异构体进行硫酸化的高度立体特异性的磺基转移酶活性。用聚乙二醇生长适合于高分辨率结构测定雌激素磺基转移酶的晶体。晶体属于正交晶体空间群P2（1）2（1）2，并衍射到2.5A。

  DOI：

  10.1016/s0006-2952(97)00465-6

文献信息

• [EN] TARGETING COMPOUNDS<br/>[FR] COMPOSÉS DE CIBLAGE
  申请人：ZAFGEN INC

  公开号：WO2019118612A1

  公开（公告）日：2019-06-20

  The disclosure provides, at least in part, liver, intestine and/or kidney-targeting compounds and their use in treating liver, intestine and/or kidney disorders, such as non-alcoholic steatohepatitis, alcoholic steatohepatitis, hepatocellular carcinoma, liver cirrhosis, and hepatitis B; and/or chronic kidney disease, glomerular disease such as IGA nephropathy, lupus nephritis, or polycystic kidney disease. The compounds are contemplated to have activity against methionyl aminopeptidase 2.

  该披露提供了至少部分针对肝脏、肠道和/或肾脏的化合物，以及它们在治疗肝脏、肠道和/或肾脏疾病中的用途，如非酒精性脂肪肝、酒精性脂肪肝、肝细胞癌、肝硬化和乙型肝炎；和/或慢性肾脏疾病、肾小球疾病，如IgA肾病、狼疮性肾炎或多囊肾病。这些化合物被认为对甲硫氨酰氨肽酶2具有活性。
• [EN] EPIANDROSTERONE AND/OR ANDROSTERONE DERIVATIVES AND METHOD OF USE THEREOF<br/>[FR] DÉRIVÉS D'ÉPIANDROSTÉRONE ET/OU D'ANDROSTÉRONE ET LEUR PROCÉDÉ D'UTILISATION
  申请人：SUTTER WEST BAY HOSPITALS DOING BUSINESS AS CALIFORNIA PACIFIC MEDICAL CT

  公开号：WO2012134446A1

  公开（公告）日：2012-10-04

  Disclosed herein are epiandrosterone and androsterone derivatives of Formula (II), process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.

  本文揭示了式（II）的雄烯酮和雄甾酮衍生物，其制备方法，药物组合物以及使用方法。
• SUBSTITUTED PYRIDINYL-PYRIMIDINES AND THEIR USE AS MEDICAMENTS
  申请人：Dahmann Georg

  公开号：US20130023502A1

  公开（公告）日：2013-01-24

  The invention relates to new substituted pyridinyl-pyrimidines of formula 1 wherein ring A is a five-membered saturated or unsaturated carbocyclic ring which optionally comprises one, two or three heteroatoms each independently from each other selected from the group N, S and O, wherein R 1 , R 2 , R 4 , R 3 , R 5 and R 6 are defined as in claim 1 and wherein ring A is further optionally substituted by one or two further substituents and the pharmaceutically acceptable salts, diastereomers, enantiomers, racemates, hydrates and solvates of the aforementioned compounds.

  该发明涉及公式1中的新取代吡啶基嘧啶化合物， 其中环A是一个含有五个成员的饱和或不饱和碳环，该环可选地包含一个、两个或三个异原子，每个异原子独立地选自N、S和O组成， 其中R1、R2、R4、R3、R5和R6如权利要求书中所定义，并且环A进一步可选地被一个或两个进一步取代基取代，以及上述化合物的药用盐、二对映体、对映体、消旋体、水合物和溶剂化合物。
• Compositions and Methods Related to Acid Stable Lipid Nanospheres
  申请人：Negrete George R.

  公开号：US20110268653A1

  公开（公告）日：2011-11-03

  The present invention relates generally to the fields of chemistry and biochemistry. More particularly, it concerns methods and compositions for the use of fatty asparagine, fatty cysteine, and fatty serine derivatives.

  本发明总体涉及化学和生物化学领域。更具体地说，它涉及使用脂肪天冬酰胺、脂肪半胱氨酸和脂肪丝氨酸衍生物的方法和组合物。
• [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。