诺龙 | 434-22-0

• 物质功能分类: 原料药 - 激素及调节内分泌功能类药 - 雄激素及同化激素类药
• 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: 诺龙
• 中文别名: 19-去甲睾酮；癸酸诺龙
• 英文名称: 19-nortestosterone
• 英文别名: 19-Nortestosteron；nandrolone；(8R,9S,10R,13S,14S,17S)-17-hydroxy-13-methyl-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-one
• CAS: 434-22-0
• 化学式: C₁₈H₂₆O₂
• mdl: MFCD00003664
• 分子量: 274.403
• InChiKey: NPAGDVCDWIYMMC-IZPLOLCNSA-N

物化性质

• 熔点：
  120-125 °C
• 比旋光度：
  D22 +55° (c = 0.93 in chloroform)
• 沸点：
  357.38°C (rough estimate)
• 密度：
  1.0528 (rough estimate)
• 闪点：
  2℃
• 溶解度：
  乙腈：1mg/mL；乙醇：1mg/mL；甲醇：1mg/mL
• 物理描述：
  Solid
• 颜色/状态：
  Dimorphic crystals
• 蒸汽压力：
  3.5X10-8 mm Hg at 25 °C (est)
• 旋光度：
  Specific optical rotation: +55 deg at 22 °C/D (c= 0.93 in chloroform)
• 碰撞截面：
  167.5 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.833
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

代谢

3-羟基雌甾烷-17-酮和雌甾烷-3,17-二醇的异构体通过气液相色谱-质谱法在接受了19-去甲睾酮的杂交马的尿液中得以识别。

Isomers of 3-hydroxyestran-17-one estrane-3,17-diol were identified by gas-liq chromatography-mass spectrometry in urine of a crossbred horse given 19-nortestosterone im.

来源:Hazardous Substances Data Bank (HSDB)

代谢

(14)C标记的去甲睾酮在小白鼠中通过宏观放射自显影进行代谢研究，在牛犊中通过液闪测定排泄和组织分布进行代谢研究。放射性物质在尿液和粪便中迅速消除。给药10周后，残留水平较低。

Metabolic studies of (14)c-labeled nortestosterone were carried out in mice by macroscopic autoradiog and in calves by liq scintillation determination of excretion and organ distribution. Radioactivity quickly eliminated in urine and feces. 10 wk after admin residual levels were low.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

鉴定：苯丙酸诺龙是一种合成类固醇。物质来源：天然存在的合成类固醇在睾丸、卵巢和肾上腺皮质中从胆固醇经孕烯醇酮合成。合成类固醇基于主要的男性激素睾酮，通过以下三种方式之一进行修改：17-碳的烷基化，17-OH基团的酯化，类固醇核的修饰。颜色：该药物为白色至乳白色固体晶体，具有轻微的特征性气味。它几乎不溶于水；溶于酒精。适应症：合成类固醇唯一合法的治疗适应症是：在男性性激素缺乏的男性中替代男性性激素，例如由于两个睾丸的丧失；治疗某些罕见的形式的再生障碍性贫血，这些贫血可能对合成雄激素有反应，或者在某些国家，这些药物被用来对抗分解状态，例如在大创伤之后。人体暴露：主要风险和靶器官：急性中毒没有严重风险，但长期使用可能造成伤害。主要风险是过量雄激素的风险：女性的月经不调和男性化，男性的阳痿、过早的心血管疾病和前列腺增生。男性和女性都可能因含有取代的17-α-碳的口服合成类固醇而遭受肝损伤。在使用这些药物期间或停药后可能会发生精神病学变化。临床效果总结：急性过量可能导致恶心和胃肠道不适。长期使用被认为会导致肌肉体积增加，并且可能引起男性特征和与男性激素相关效果的夸张。合成类固醇可以影响性功能。它们还可能导致心血管和肝脏损伤。男女都可能发生痤疮和男性型秃发；女性可能出现月经不调、乳房萎缩和阴蒂肥大；男性可能出现睾丸萎缩和前列腺增生。禁忌症：已知或疑似前列腺癌（在男性中）或乳腺癌、妊娠或哺乳，以及已知的心血管疾病是相对禁忌症。暴露途径：口服：合成类固醇可以从胃肠道吸收，但许多化合物在肝脏中首次通过代谢如此广泛，以至于它们变得无效。那些在17-碳位置取代的化合物，可以保护化合物免受肝脏的快速代谢，口服时是有效的。有一些睾酮制剂可以舌下含服。注射：除了17-α-取代的类固醇（口服有效）之外，所有合成类固醇的主要给药途径是肌肉内或深部皮下注射。暴露途径的吸收：口服给药后的吸收是快速的，对于睾酮和其他合成类固醇可能也是如此，但对于所有合成类固醇（除了在17-α位置取代的类固醇）都有广泛的首过肝代谢。从皮下或肌肉内储存库的吸收速率取决于产品和其配方。对于像环戊酸酯或恩诺龙这样的脂溶性酯以及油性悬浮液，吸收是缓慢的。暴露途径的分布：合成类固醇高度与蛋白质结合，并通过一种称为性激素结合球蛋白的特定蛋白质在血浆中携带。暴露途径的生物半衰期：吸收药物的代谢是快速的，从血浆中的消除半衰期非常短。因此，生物效应的持续时间几乎完全取决于从皮下或肌肉内储存库的吸收速率，以及在此之前的脱酯化过程。代谢：自由的（脱酯化的）合成雄激素通过肝脏的混合功能氧化酶代谢。暴露途径的消除：给予放射性标记的睾酮后，大约90%的放射性出现在尿液中，6%出现在粪便中；有一些肠肝循环。作用方式：毒动力学：毒性效应是正常药理效应的夸张。药动力学：合成类固醇与特别是在生殖组织、肌肉和脂肪中存在的特定受体结合。合成类固醇减少在雄激素缺乏男性中组织分解的氮排泄。它们还负责正常的男性性分化。在该类药物中，成员之间的合成（身体建设）效果与雄性化（男性化）效果的比例可能不同，但实际上所有药物都不同程度地具有这两种性质。没有明确证据表明合成类固醇能提高整体运动性能。致癌性：合成类固醇可能具有致癌性。它们可以刺激依赖性激素的组织的生长，主要是男性中的前列腺。在长期滥用合成类固醇后，已经描述了早熟的前列腺癌。已经报道了与合成类固醇滥用相关的肝细胞癌病例。致畸性：孕妇摄入雄激素可能导致女性胎儿的男性化。主要不良影响：合成类固醇的不良影响包括体重增加、液体潴留和通过生化测试测量的异常肝功能。给孩子使用可能导致骨骺的过早闭合。男性可能会发展成阳痿和无精子症。女性有男性化的风险。/苯丙酸诺龙/

IDENTIFICATION: Nandrolone phenylpropionate is an anabolic steroid. Origin of the substance: Naturally occuring anabolic steroids are synthesised in the testis, ovary and adrenal gland from cholesterol via pregnenolone. Synthetic anabolic steroids are based on the principal male hormone testosterone, modified in one of three ways: alkylation of the 17-carbon, esterification of the 17-OH group, modification of the steroid nucleus. Color: The drug is white to creamy white solid crystals with a slight characteristic odor. It is practically insoluble in water; soluble in alcohol. Indications: The only legitimate therapeutic indications for anabolic steroids are: replacement of male sex steroids in men who have androgen deficiency, for example as a result of loss of both testes; the treatment of certain rare forms of aplastic anemia which are or may be responsive to anabolic androgens, or the drugs have been used in certain countries to counteract catabolic states, for example after major trauma. HUMAN EXPOSURE: Main risks and target organs: There is no serious risk from acute poisoning, but chronic use can cause harm. The main risks are those of excessive androgens: menstrual irregularities and virilization in women and impotence, premature cardiovascular disease and prostatic hypertrophy in men. Both men and women can suffer liver damage with oral anabolic steroids containing a substituted 17-alpha-carbon. Psychiatric changes can occur during use or after cessation of these agents. Summary of clinical effects: Acute overdosage can produce nausea and gastrointestinal upset. Chronic usage is thought to cause an increase in muscle bulk, and can cause an exaggeration of male characteristics and effects related to male hormones. Anabolic steroids can influence sexual function. They can also cause cardiovascular and hepatic damage. Acne and male- pattern baldness occur in both sexes; irregular menses, atrophy of the breasts, and clitoromegaly in women; and testicular atrophy and prostatic hypertrophy in men. Contraindications: Known or suspected cancer of the prostate or (in men) breast, pregnancy or breast-feeding, and known cardiovascular disease is a relative contraindication. ROUTES OF EXPOSURE: Oral: Anabolic steroids can be absorbed from the gastrointestinal tract, but many compounds undergo such extensive first pass metabolism in the liver that they are inactive. Those compounds in which substitution of the 17- carbon protects the compound from the rapid hepatic metabolism are active orally. There are preparations of testosterone that can be taken sublingually. Parenteral: Intramuscular or deep subcutaneous injection is the principal route of administration of all the anabolic steroids except the 17-alpha-substituted steroids which are active orally. Absorption by route of exposure: The absorption after oral dosing is rapid for testosterone and probably for other anabolic steroids, but there is extensive first-pass hepatic metabolism for all anabolic steroids except those that are substituted at the 17-alpha position. The rate of absorption from subcutaneous or intramuscular depots depends on the product and its formulation. Absorption is slow for the lipid-soluble esters such as the cypionate or enanthate, and for oily suspensions. Distribution by route of exposure: The anabolic steroids are highly protein bound, and is carried in plasma by a specific protein called sex-hormone binding globulin. Biological half-life by route of exposure: The metabolism of absorbed drug is rapid, and the elimination half-life from plasma is very short. The duration of the biological effects is therefore determined almost entirely by the rate of absorption from subcutaneous or intramuscular depots, and on the de-esterification which precedes it. Metabolism: Free (de-esterified) anabolic androgens are metabolized by hepatic mixed function oxidases. Elimination by route of exposure: After administration of radiolabelled testosterone, about 90% of the radioactivity appears in the urine, and 6% in the feces; there is some enterohepatic recirculation. Mode of action: Toxicodynamics: The toxic effects are an exaggeration of the normal pharmacological effects. Pharmacodynamics: Anabolic steroids bind to specific receptors present especially in reproductive tissue, muscle and fat. The anabolic steroids reduce nitrogen excretion from tissue breakdown in androgen deficient men. They are also responsible for normal male sexual differentiation. The ratio of anabolic (body-building) effects to androgenic (virilizing) effects may differ among the members of the class, but in practice all agents possess both properties to some degree. There is no clear evidence that anabolic steroids enhance overall athletic performance. Carcinogenicity: Anabolic steroids may be carcinogenic. They can stimulate growth of sex-hormone dependent tissue, primarily the prostate gland in men. Precocious prostatic cancer has been described after long-term anabolic steroid abuse. Cases where hepatic cancers have been associated with anabolic steroid abuse have been reported. Teratogenicity: Androgen ingestion by a pregnant mother can cause virilization of a female fetus. Main adverse effects: The adverse effects of anabolic steroids include weight gain, fluid retention, and abnormal liver function as measured by biochemical tests. Administration to children can cause premature closure of the epiphyses. Men can develop impotence and azoospermia. Women are at risk of virilization. /Nandrolone phenylpropionate/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

在同时使用同化类固醇，尤其是17-α-烷基化化合物时，由于改变了促凝血因子的合成或分解以及增加了抗凝血剂的受体亲和力，导致促凝血因子浓度降低，可能会增加抗凝作用；在并用药期间和之后，可能需要根据凝血酶原时间测定来调整抗凝剂的剂量。/同化类固醇/

Anticoagulant effect may be increased during concurrent use with anabolic steroids, especially 17-alpha-alkylated compounds, because of decreased procoagulant factor concentration caused by alteration of procoagulant factor synthesis or catabolism and increased receptor affinity for the anticoagulant; anticoagulant dosage adjustment based on prothrombin time determinations may be required during and following concurrent use. /Anabolic steroids/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

类固醇可能会降低血糖浓度；糖尿病患者应该被密切监测低血糖的迹象，并根据需要调整降糖药的剂量。/类固醇/

Anabolic steroids may decrease blood glucose concentrations; diabetic patients should be closely monitored for signs of hypoglycemia and dosage of hypoglycemic agent adjusted as necessary. /Anabolic steroids/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

糖皮质激素（尤其是具有显著盐皮质激素活性的那些）；盐皮质激素；促肾上腺皮质激素，尤其是长期治疗使用；或含钠药物或食物与同化甾体同时使用可能增加水肿的可能性；此外，糖皮质激素或促肾上腺皮质激素与同化甾体同时使用可能促进严重痤疮的发展。/同化甾体/

Concurrent use /of glucocorticoid corticosteroids, especially with significant mineralocorticoid activity; mineralocorticoid corticosteroids; corticotropin, especially prolonged therapeutic use; or sodium-containing medications or foods/ with anabolic steroids may increase the possibility of edema; in addition, concurrent use of glucocorticoids or corticotropin with anabolic steroids may promote development of severe acne. /Anabolic steroids/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

合成代谢类固醇与生长激素释放肽或生长激素同时使用可能会加速骨骺的成熟。/合成代谢类固醇/

Concurrent use of anabolic steroids with somatrem or somatropin may accelerate epiphyseal maturation. /Anabolic steroids/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

(14)C标记的去甲睾酮在小鼠和犊牛中的代谢研究进行了。放射性物质主要通过尿液和粪便快速排出。给药10周后，残留水平较低。快速吸收和消除可能在兽医使用中很重要。

Metabolic studies of (14)c-labe nortestosterone were carried out in mice and in calves. Radioactivity was quickly eliminated mainly in urine and feces. 10 wk after admin residual levels were low. Rapid absorption and elimination may be important in vet use.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

尚不清楚合成代谢类固醇是否分布到母乳中。/合成代谢类固醇/

It is not known whether anabolic steroids are distributed into breast milk. /Anabolic steroids/

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S22,S24/25,S36/37/39
• 危险类别码：
  R20/21/22
• WGK Germany：
  3
• 海关编码：
  2937290021
• 危险品运输编号：
  NONH for all modes of transport
• RTECS号：
  KG7964000

制备方法与用途

检测

诺龙具有较强的毒副作用，可引起癌症、肝炎和神经混乱。在功能食品中恶意掺加诺龙极易对人体造成危害，因此对功能食品中诺龙的检测具有重要意义。

由于17β-NT在功能食品中的添加量很少，并且功能食品成分复杂，基质干扰难以消除，常规检测方法很难达到理想的检测效果。因此迫切需要建立一种经济、可靠、特异、灵敏、快速有效的方法。

有研究开发了一种最大程度保留诺龙结构的人工半抗原、抗原和抗体的制备方法。通过化学合成方法制得的诺龙半抗原与载体BSA蛋白连接，合成人工抗原；随后利用人工抗原免疫动物，并从其血液中提取并纯化得到特异性高抗体。此方法在设计上突出了分子特异性抗原决定簇，同时克服了化学合成的困难。

与其他同类方法相比，该方法具有特异、灵敏、准确、快速、方便和经济等特点，为制备特异性良好的抗体奠定了基础。

药物相关作用

1. 可增强抗凝血药香豆素、华法令等药物的抗凝作用；
2. 与皮质激素合用时，可使血糖升高。

用途

用于运动营养保健品。

反应信息

• 作为反应物：
  描述：

  诺龙 在 N-溴代丁二酰亚胺(NBS) 、 安息香双甲醚 、 水 、 双氧水 、 对甲苯磺酸 、 溶剂黄146 、 copper(I) bromide 、 lithium bromide 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 55.5h， 生成 氟维司群
  参考文献：
  名称：

  [EN] PROCESS AND INTERMEDIADES FOR THE PREPARATION OF 7-ALKYLATED STEROIDS
  [FR] PROCÉDÉ ET INTERMÉDIAIRES POUR LA PRÉPARATION DE STÉROÏDES 7-ALKYLÉS

  摘要：

  一种制备式(I)化合物的方法，或者其盐、溶剂合物或立体异构体，包括富马酸苯甲酸酯（Fulvestrant）的方法，该方法包括自由基向式(III)化合物转化的步骤，或者其盐、溶剂合物或立体异构体。该发明还涉及所述方法的中间体。

  公开号：

  WO2015181116A1
• 作为产物：
  描述：

  (1S,7aS)-1-hydroxy-7a-methyl-2,3,7,7a-tetrahydro-1H-inden-5(6H)-one 在 磷酸 、 palladium 10% on activated carbon 、 三氟化硼乙醚 、 氢气 、 sodium methylate 、 三乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 11.0h， 生成 诺龙
  参考文献：
  名称：

  [EN] C-20 STEROID COMPOUNDS, COMPOSITIONS AND USES THEREOF TO TREAT TRAUMATIC BRAIN INJURY (TBI), INCLUDING CONCUSSIONS
  [FR] COMPOSÉS STÉROÏDES EN C-20, COMPOSITIONS ET UTILISATIONS ASSOCIÉES POUR TRAITER UNE LÉSION CÉRÉBRALE TRAUMATIQUE (TBI), NOTAMMENT DES COMMOTIONS

  摘要：

  本发明涉及C-20类固醇化合物，其组合物和使用方法，用于治疗、减轻和/或预防创伤性脑损伤（TBI），包括严重TBI、中度TBI和轻度TBI，包括脑震荡。

  公开号：

  WO2016044559A1

文献信息

• Anti-angiogenic compounds
  申请人：Bradshaw W. Curt

  公开号：US20060205670A1

  公开（公告）日：2006-09-14

  The present invention provides AA targeting compounds which comprise AA targeting agent-linker conjugates which are linked to a combining site of an antibody. Various uses of the compounds are provided, including methods to treat disorders connected to abnormal angiogenesis.

  本发明提供了包括与抗体的结合位点连接的AA靶向剂-连接剂共轭物的AA靶向化合物。提供了化合物的各种用途，包括治疗与异常血管生成相关的疾病的方法。
• [EN] MACROCYLIC PYRIDINE DERIVATIVES<br/>[FR] DÉRIVÉS DE PYRIDINE MACROCYCLIQUES
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2015150557A1

  公开（公告）日：2015-10-08

  The present invention relates to substituted macrocylic pyrimidine derivatives of Formula (I) wherein the variables have the meaning defined in the claims. The compounds according to the present invention have EF2K inhibitory activity and optionally also Vps34 inhibitory activity. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

  本发明涉及式（I）的取代大环嘧啶衍生物，其中变量的含义如权利要求中所定义。根据本发明的化合物具有EF2K抑制活性，还可能具有Vps34抑制活性。本发明还涉及制备这种新化合物的方法，包含所述化合物作为活性成分的药物组合物，以及将所述化合物用作药物的用途。
• [EN] ISOINDOLINONE INHIBITORS OF THE MDM2-P53 INTERACTION AND PROCESS FOR MAKING THEM<br/>[FR] INHIBITEURS ISOINDOLINONE DE L'INTERACTION MDM2-P53 ET PROCÉDÉS DE PRÉPARATION DE CES DERNIERS
  申请人：ASTEX THERAPEUTICS LTD

  公开号：WO2018178691A1

  公开（公告）日：2018-10-04

  The invention relates to processes for preparing isoindolin-1-one derivatives, and in particular processes for preparing (2S,3S)-3-(4-chlorophenyl)-3-[(1R)-1-(4-chlorophenyl)-7-fluoro-5-[(1S)-1-hydroxy-1- (oxan-4-yl)propyl]-1-methoxy-3-oxo-2,3-dihydro-1H-isoindol-2-yl]-2-methylpropanoic acid. The invention also relates to crystalline forms of the compound (2S,3S)-3-(4-chlorophenyl)-3-[(1R)-1-(4- chlorophenyl)-7-fluoro-5-[(1S)-1-hydroxy-1-(oxan-4-yl)propyl]-1-methoxy-3-oxo-2,3-dihydro-1H- isoindol-2-yl]-2-methylpropanoic acid and its salts.

  该发明涉及制备异吲哚啉-1-酮衍生物的方法，特别是制备(2S,3S)-3-(4-氯苯基)-3-[(1R)-1-(4-氯苯基)-7-氟-5-[(1S)-1-羟基-1-(氧戊-4-基)丙基]-1-甲氧基-3-酮基-2,3-二氢-1H-异吲哚-2-基]-2-甲基丙酸的方法。该发明还涉及化合物(2S,3S)-3-(4-氯苯基)-3-[(1R)-1-(4-氯苯基)-7-氟-5-[(1S)-1-羟基-1-(氧戊-4-基)丙基]-1-甲氧基-3-酮基-2,3-二氢-1H-异吲哚-2-基]-2-甲基丙酸及其盐的晶型形式。
• [EN] ANTICANCER BENZOPYRAZINES VIA THE INHIBITION OF FGFR KINASES<br/>[FR] BENZOPYRAZINES ANTICANCÉREUSES PAR LE BIAIS DE L'INHIBITION DE FGFR KINASES
  申请人：ASTEX THERAPEUTICS LTD

  公开号：WO2013061081A1

  公开（公告）日：2013-05-02

  The invention relates to new quinoxaline derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

  这项发明涉及新的喹啉衍生物化合物，包括含有该化合物的药物组合物，用于制备该化合物的方法以及该化合物在治疗疾病（例如癌症）中的用途。
• Synthesis of 13-alkyl-gon-4-ones
  申请人：Smith; Herchel

  公开号：US03959322A1

  公开（公告）日：1976-05-25

  The preparation of 13-methylgon-4-enes and novel 13-polycarbonalkylgon-4-enes by a new total synthesis is described. 13-Alkylgon-4-enes having progestational, anabolic and androgenic activities are prepared by forming a tetracylic gonane structure unsaturated in the 1,3,5(10),9(11) and 14-positions, selectively reducing in the B- and C-rings, and converting the aromatic A-ring compounds so-produced to gon-4-enes by Birch reduction and hydrolysis.

  描述了通过新的全合成方法制备13-甲基孕-4-烯和新型13-聚碳烷基孕-4-烯。通过形成在1,3,5(10),9(11)和14-位置不饱和的四环孕烷结构，选择性地在B和C环中还原，并将所产生的芳香A环化合物转化为孕-4-烯，制备具有孕激素、合成激素和雄激素活性的13-烷基孕-4-烯。

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