群勃龙 | 10161-33-8

• 物质功能分类: 原料药 - 激素及调节内分泌功能类药 - 避孕药
• 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: 群勃龙
• 中文别名: 孕三烯酮；群勃龙庚酸脂
• 英文名称: trenbolone
• 英文别名: Δ^9(10),11-19-nortestosterone；17β-hydroxy-estra-4,9,11-trien-3-one；17-β-hydroxyestra-4,9,11-trien-3-one；17β-hydroxyestra-4,9,11-trien-3-one；Estra-4,9,11-trien-17β-ol-3-on；(8S,13S,14S,17S)-17-hydroxy-13-methyl-2,6,7,8,14,15,16,17-octahydro-1H-cyclopenta[a]phenanthren-3-one
• CAS: 10161-33-8
• 化学式: C₁₈H₂₂O₂
• 分子量: 270.371
• InChiKey: MEHHPFQKXOUFFV-OWSLCNJRSA-N

物化性质

• 熔点：
  170°C
• 比旋光度：
  D20 +19° (c = 0.45 in ethanol)
• 沸点：
  490.8±45.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)
• 闪点：
  2℃
• 溶解度：
  DMF：30 mg/ml； DMF:PBS (pH 7.2)(1:3)：0.25 mg/ml； DMSO：20 mg/ml；乙醇：2 mg/ml
• 碰撞截面：
  163.3 Ų [M+H]+ [CCS Type: TW]
• 稳定性/保质期：
  遵照规格使用和储存不会分解。

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.611
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险品标志：
  T
• 安全说明：
  S22,S36/37/39,S45,S53
• 危险类别码：
  R60
• WGK Germany：
  3
• RTECS号：
  KG7752000
• 海关编码：
  2942000000

制备方法与用途

群勃龙的生物学作用

多数同化激素通过睾酮的活动发挥作用，如合成代谢（Anabolism）和男性化（virilization）效应。例如：

• 促进氨基酸参与蛋白质生物合成；
• 促使肌肉生长与增大；
• 增强食欲；
• 加速骨骼发育；
• 刺激骨髓活动，增加红细胞生成。

在促合成作用方面，群勃龙的效果比睾酮或大力补更为显著。

群勃龙的特性

群勃龙是一种人工合成的三烯19-去甾甲类化合物，其抗雌激素和抗孕激素活性可以非常强烈或者较弱。它主要通过作用于丘脑下部和垂体轴来减少促性腺素释放，从而抑制排卵高峰。实验表明，群勃龙能够抑制孕激素分泌，并具备黄体酮对子宫内膜的作用，使子宫内膜及异位病灶细胞失活、退化，进而导致异位病灶萎缩。

群勃龙的抗生育作用

其抗生育效果可能是通过以下途径实现：

• 抑制排卵；
• 抑制子宫内膜发育；
• 改变宫颈粘液性质，影响受精卵运动；
• 拮抗子宫内膜孕酮受体，干扰胚胎着床。

群勃龙的应用

群勃龙作为雄激素和同化激素类药物之一，常用于治疗子宫内膜异位症。然而，在畜牧业中，少数企业因追求最大利润而滥用或非法使用此类药品。因此，大量群勃龙可能在动物源性食品中残留超量，最终对人体健康产生不良影响。

结论

随着畜牧业的发展和规模化、集约化的推进，一些饲养者与经营者可能会忽视国家法律法规，过度使用激素类违禁药品作为饲料添加剂，导致群勃龙在食物中的残留超标。消费者食用这些受污染的食物后，可能会出现多种不良反应，直接威胁健康甚至生命安全。

反应信息

• 作为反应物：
  描述：

  群勃龙 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 生成 三烯
  参考文献：
  名称：

  Synthesis and SAR study of novel pseudo-steroids as potent and selective progesterone receptor antagonists

  摘要：

  Synthesis of novel 7-pseudo-steroids 1c has been achieved from trenbolone 3 via an efficient 14 step sequence with overall yields of 10-15%. Various substitutions were incorporated at both the aromatic side chain as well as the D ring. The orientation of aromatic side chain at C10 plays a crucial role for progesterone receptor (PR) activity. Compound 2a (T47D = 1 nM) with -NMe2 para to the aromatic group along with spirofurane groups in the D ring was the optimal substitution. All compounds were also evaluated for glucocorticoid receptor (GR) antagonist activities in vivo in a rat and found efficacious in uterine complement C3 assay via the oral route of administrations. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.01.095
• 作为产物：
  描述：

  3-缩酮 在 钾硼氢 、 硫酸 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 正丁醇 作用下， 以 二氯甲烷 、 水 、 丙酮 为溶剂， 生成 群勃龙
  参考文献：
  名称：

  一种制备群勃龙醋酸酯的方法

  摘要：

  本发明公开了一种制备群勃龙醋酸酯的方法，属于激素类药物的制备加工技术领域。该方法以3‑亚乙二氧基雌甾‑Δ 5,10 ，Δ 9,11 ‑二烯‑17‑酮为起始原料，通过还原17位酮为醇，水解3位缩酮，氧化脱氢和17位醇乙酰化制备得到群勃龙醋酸酯。本发明所述的群勃龙醋酸酯合成工艺路线，原料价廉易得，反应控制简便副产物少，纯化容易，总产率高，在生产成本和可操作性上有极高的竞争力，适合工业化大规模生产，具有良好的经济效益。

  公开号：

  CN110437294A

文献信息

• [EN] 5-HT2C RECEPTOR AGONISTS AND COMPOSITIONS AND METHODS OF USE<br/>[FR] AGONISTES DE RÉCEPTEUR 5-HT2C ET COMPOSITIONS ET PROCÉDÉS D'UTILISATION
  申请人：ARENA PHARM INC

  公开号：WO2017023679A1

  公开（公告）日：2017-02-09

  Provided in some embodiments are compounds of Formula A, as defined herein, that modulate the activity of 5-HT2C receptor. Also provided in some embodiments are methods, such as, for weight management, inducing satiety, and decreasing food intake, and for preventing and treating obesity, antipsychotic-induced weight gain, type 2 diabetes, Prader-Willi syndrome, tobacco/nicotine dependence, drug addiction, alcohol addiction, pathological gambling, reward deficiency syndrome, and sex addiction), obsessive-compulsive spectrum disorders and impulse control disorders (including nail-biting and onychophagia), sleep disorders (including insomnia, fragmented sleep architecture, and disturbances of slow-wave sleep), urinary incontinence, psychiatric disorders (including schizophrenia, anorexia nervosa, and bulimia nervosa), Alzheimer disease, sexual dysfunction, erectile dysfunction, epilepsy, movement disorders (including parkinsonism and antipsychotic-induced movement disorder), hypertension, dyslipidemia, nonalcoholic fatty liver disease, obesity-related renal disease, and sleep apnea.

  在某些实施例中提供了一些符合本文所定义的A式化合物，其调节5-HT2C受体的活性。在某些实施例中还提供了一些方法，例如用于体重管理、诱导饱腹感、减少食物摄入，以及预防和治疗肥胖、抗精神病药物引起的体重增加、2型糖尿病、普拉德-威利综合征、烟草/尼古丁依赖、药物成瘾、酒精成瘾、病理性赌博、奖赏缺乏综合征和性成瘾，强迫症谱系障碍和冲动控制障碍（包括咬指甲和咬甲症），睡眠障碍（包括失眠、睡眠结构碎裂和慢波睡眠紊乱），尿失禁，精神障碍（包括精神分裂症、厌食症和暴食症），阿尔茨海默病，性功能障碍，勃起功能障碍，癫痫，运动障碍（包括帕金森病和抗精神病药物引起的运动障碍），高血压，血脂异常，非酒精性脂肪肝病，肥胖相关肾脏疾病和睡眠呼吸暂停症。
• Nitric Oxide Releasing Prodrugs of Therapeutic Agents
  申请人：SATYAM Apparao

  公开号：US20110263526A1

  公开（公告）日：2011-10-27

  The present invention relates to nitric oxide releasing prodrugs of known drugs or therapeutic agents which are represented herein as compounds of formula (I) wherein the drugs or therapeutic agents contain one or more functional groups independently selected from a carboxylic acid, an amino, a hydroxyl and a sulfhydryl group. The invention also relates to processes for the preparation of the nitric oxide releasing prodrugs (the compounds of formula (I)), to pharmaceutical compositions containing them and to methods of using the prodrugs.

  本发明涉及已知药物或治疗剂的一氧化氮释放前药，其在此处表示为式(I)的化合物，其中药物或治疗剂包含一个或多个功能基团，独立地选自羧酸、氨基、羟基和巯基。该发明还涉及制备一氧化氮释放前药（式(I)的化合物）的方法，含有它们的药物组合物以及使用这些前药的方法。
• [EN] 5-HT2C RECEPTOR AGONISTS AND COMPOSITIONS AND METHODS OF USE<br/>[FR] AGONISTES DU RÉCEPTEUR 5-HT2C ET COMPOSITIONS ET PROCÉDÉS D'UTILISATION
  申请人：ARENA PHARM INC

  公开号：WO2015066344A1

  公开（公告）日：2015-05-07

  Provided are 5-HT2C receptor agonists. Also provided are methods for weight management, inducing satiety, and decreasing food intake, and for preventing and treating obesity, antipsychotic-induced weight gain, type 2 diabetes, Prader-Willi syndrome, tobacco/nicotine dependence, drug addiction, alcohol addiction, pathological gambling, reward deficiency syndrome, and sex addiction), obsessive-compulsive spectrum disorders and impulse control disorders (including nail-biting and onychophagia), sleep disorders (including insomnia, fragmented sleep architecture, and disturbances of slow-wave sleep), urinary incontinence, psychiatric disorders (including schizophrenia, anorexia nervosa, and bulimia nervosa), Alzheimer disease, sexual dysfunction, erectile dysfunction, epilepsy, movement disorders (including parkinsonism and antipsychotic-induced movement disorder), hypertension, dyslipidemia, nonalcoholic fatty liver disease, obesity-related renal disease, and sleep apnea. Also provided are compositions comprising a selective 5-HT2C receptor agonist, optionally in combination with a supplemental agent, and methods for reducing the frequency of smoking tobacco in an individual attempting to reduce frequency of smoking tobacco; aiding in the cessation or lessening of use of a tobacco product in an individual attempting to cease or lessen use of a tobacco product; aiding in smoking cessation and preventing associated weight gain; controlling weight gain associated with smoking cessation by an individual attempting to cease smoking tobacco; reducing weight gain associated with smoking cessation by an individual attempting to cease smoking tobacco; treating nicotine dependency, addiction and/or withdrawal in an individual attempting to treat nicotine dependency, addiction and/or withdrawal; or reducing the likelihood of relapse use of nicotine by an individual attempting to cease nicotine use comprising administering a selective 5-HT2C receptor agonist, optionally in combination with a supplemental agent.

  提供了5-HT2C受体激动剂。还提供了用于体重管理、诱导饱腹感、减少食物摄入量、预防和治疗肥胖、抗精神病药物引起的体重增加、2型糖尿病、普拉德-威利综合征、烟草/尼古丁依赖、药物成瘾、酒精成瘾、病态赌博、奖赏缺乏综合征和性成瘾）、强迫症谱系障碍和冲动控制障碍（包括咬指甲和咬甲）、睡眠障碍（包括失眠、睡眠结构碎裂和慢波睡眠紊乱）、尿失禁、精神障碍（包括精神分裂症、厌食症和暴食症）、阿尔茨海默病、性功能障碍、勃起功能障碍、癫痫、运动障碍（包括帕金森病和抗精神病药物引起的运动障碍）、高血压、血脂异常、非酒精性脂肪肝病、肥胖相关肾脏疾病和睡眠呼吸暂停。还提供了包含选择性5-HT2C受体激动剂的组合物，可选地与辅助剂结合，以及用于减少个体尝试减少吸烟频率的吸烟频率；帮助个体戒除或减少使用烟草制品的个体戒除或减少使用烟草制品；帮助戒烟并预防相关体重增加；通过个体尝试戒烟来控制与戒烟相关的体重增加；通过个体尝试戒烟来减少与戒烟相关的体重增加；治疗尼古丁依赖、成瘾和/或戒断的个体尝试治疗尼古丁依赖、成瘾和/或戒断；或减少个体尝试戒除尼古丁使用的复发可能性，包括给予选择性5-HT2C受体激动剂，可选地与辅助剂结合。
• Somatostatin antagonists and agonists
  申请人：——

  公开号：US20020091090A1

  公开（公告）日：2002-07-11

  Compounds according to the formula A-B-Z-W, wherein A is selected from (C 6 -C 10 )aryl-, or (C 1 -C 9 )heteroaryl-, which groups may be optionally substituted; B is selected from (a) O, NH, NR 10 , —(CH 2 ) k —O—, —(CH 2 ) k —N—, and —(CH 2 ) k —NR 10 —, where R 10 is (C 1 -C 6 )alkyl and where k is 1 to 6 in each case, or 1 where said group (i) through (iv) is optionally substituted by 1 to 4, preferably 1 to 2, groups selected from (C 1 -C 6 )alkyl, halo, and (C 1 -C 6 )alkyl optionally substituted by 1 to 3 halo atoms wherein one of carbon atoms C 1 , C 2 , C 3 and C 4 of said piperidine or piperazine group is optionally replaced by a carbonyl group; Z and W are as herein described; and pharmaceutically acceptable salts, solvates or hydrates thereof; pharmaceutical compositions thereof; and methods useful to facilitate secretion of growth hormone(GH) in mammels.

  根据公式A-B-Z-W，其中 A选自(C6-C10)芳基或(C1-C9)杂环芳基，这些基团可以选择性地被取代； B选自 (a) O、NH、NR10、—(CH2)k—O—、—(CH2)k—N—和—(CH2)k—NR10—，其中R10为(C1-C6)烷基，k在每种情况下为1至6，或 1所述的该组(i)至(iv)可以选择性地被1至4个，优选1至2个，选自(C1-C6)烷基、卤素和(C1-C6)烷基，该烷基可以选择性地被1至3个卤原子取代，其中所述哌啶或哌嗪基团的碳原子C1、C2、C3和C4中的一个可以选择性地被羰基取代； Z和W如本文所述；以及其药学上可接受的盐、溶剂化合物或水合物；其制药组合物；以及用于促进哺乳动物分泌生长激素(GH)的方法。
• Profiling 19-norsteroids. I—tandem mass spectrometric characterization of the heptafluorobutyryl ester and pentafluorobenzyloxime heptafluorobutyryl ester derivatives of 19-nortestosterone using collisionally activated dissociation
  作者：D. de Boer、S. N. Bensink、A. R. Borggreve、R. D. van Ooijen、R. A. A. Maes

  DOI：10.1002/jms.1190300316

  日期：1995.3

  Tandem mass spectrometric methods for the identification of 19-nortestosterone (estr-4-en-17β-3-one) are described and evaluated. The fragmentation reactions of the heptafluorobutyryl (HFB) and pentafluorobenzyloxime heptafluorobutyryl (PFBOHFB) ester derivatives of 19-nortestosterone in particular were studied for the purpose to select characteristic ions. The HFB ester was analyzed by collisionly activated dissociation (CAD) following electron impact in order to fragment the steroid nucleus. Cleavage of the A-ring, i.e. the ring containing the keto function, was prominent. The formation of A-, A/B- and D-ring fragments was also typical for this type of derivative. The PFBOHFB ester was formed to create a derivative, which could capture electrons and be analyzed in the electron-capture negative chemical ionization (ECNCI) mode. Besides fragmentations originating in the groups coupled to the steroid by derivatization, no prominent steroid nucleus fragmentations were observed by CAD following ECNCI. Accordingly, of both methods only CAD following EI of the HFB derivative of 19-nortestosterone provided a characteristic MS/MS procedure for the identification of 19-nortestosterone.

  本文描述并评估了用于鉴定19-诺特孕甾酮（estr-4-en-17β-3-one）的串联质谱方法。特别是研究了19-诺特孕甾酮的七氟丁酰（HFB）和五氟苯甲肟七氟丁酰（PFBOHFB）酯衍生物的碎裂反应，目的是选择特征离子。通过电子轰击后的碰撞活化裂解（CAD）分析HFB酯，以裂解甾体核心。A环的断裂，即含有酮基的环，非常显著。A环、A/B环和D环碎片的形成也是这类衍生物的典型特征。形成PFBOHFB酯是为了创造一种能够捕获电子并以电子捕获负化学电离（ECNCI）模式分析的衍生物。除了衍生化过程中与甾体连接的基团产生的碎裂外，通过ECNCI后的CAD没有观察到显著的甾体核心碎裂。因此，这两种方法中，只有HFB衍生物的EI后CAD为19-诺特孕甾酮的鉴定提供了一种特征性的MS/MS程序。