alpha-(1-氨基乙基)-苯甲醇 | 48115-38-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: alpha-(1-氨基乙基)-苯甲醇
• 英文名称: norephedrin
• 英文别名: phenylpropanolamine；2-Amino-1-phenyl-1-propanol；2-amino-1-phenylpropan-1-ol
• CAS: 48115-38-4
• 化学式: C₉H₁₃NO
• 分子量: 151.208
• InChiKey: DLNKOYKMWOXYQA-UHFFFAOYSA-N

物化性质

• 熔点：
  103 °C
• 沸点：
  122 °C(Press: 4-5 Torr)
• 密度：
  1.071±0.06 g/cm3(Predicted)
• 颜色/状态：
  White, crystalline powder
• 气味：
  Slight aromatic odor
• 溶解度：
  In water, 1.49X10+5 mg/L at 25 °C (est)
• 蒸汽压力：
  8.67X10-4 mm Hg at 25 °C (est)
• 分解：
  When heated to decomposition it emits very toxic fumes of nitroxides.
• 解离常数：
  pKa = 9.44 (conjugate acid)
• 保留指数：
  1313;1350

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  46.2
• 氢给体数：
  2
• 氢受体数：
  2

ADMET

代谢

与其他苯丙醇胺类药物一样，少量的药物在肝脏中被缓慢代谢为活性羟基代谢物。大约80-90%的苯丙醇胺剂量在24小时内以原形从尿液中排出。/盐酸苯丙醇胺/

Like other phenylisopropanolamines, small amounts of the drug are slowly metabolized in the liver to an active hydroxylated metabolite. About 80-90% of a dose of phenylpropanolamine is excreted unchanged in the urine within 24 hours. /Phenylpropanolamine hydrochloride/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

使用安非他明、非那西丁和三环类抗抑郁药时，甲基多巴的抗高血压作用会减弱。

With amphetamines, phenylpropanolamine, and the tricyclic antidepressants, the antihypertensive effects of methyldopa are lessened.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

盐酸苯丙醇胺与吲哚美辛的联合使用与一例患者的严重高血压有关；当单独使用任一药物时并未发生高血压。/盐酸苯丙醇胺/

Concomitant use /of/ phenylpropanolamine and indomethacin was associated with severe hypertension in one patient; hypertension did not occur when either drug was used alone. /Phenylpropanolamine hydrochloride/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

将苯丙醇胺给药于接受过环丙烷或卤化烃类全麻药物的患者可能会导致心律不齐。如果出现心律不齐，可能会对给予普萘洛尔（一种β-肾上腺素能阻断剂）有反应。/盐酸苯丙醇胺/

Administration of phenylpropanolamine to patients who have received cyclopropane or halogenated hydrocarbon general anesthetics may result in arrhythmias. Arrhythmias, if they occur, may respond to administration of propranolol, a beta-adrenergic blocking agent. /Phenylpropanolamine hydrochloride/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

咖啡因和苯丙醇胺的效果是通过激活中枢和交感神经系统来介导的。据报道，它们联合使用后会出现严重、威胁生命且偶尔致命的高血压反应。本研究探讨了苯丙醇胺和咖啡因可能的药物动力学相互作用。十六名正常受试者接受了咖啡因、苯丙醇胺和安慰剂的组合。在接受400毫克咖啡因加75毫克苯丙醇胺的受试者中，咖啡因血浆峰浓度的平均值（±SEM）为8.0 ± 2.2微克/毫升，显著高于单独使用400毫克咖啡因（2.1 ± 0.3微克/毫升；t(24) = 2.4；p < 0.01）。苯丙醇胺-咖啡因组合的物理副作用发生频率高于单独使用任一药物或安慰剂。组合使用后，收缩压和舒张压的增加幅度大于单独使用任一药物。这些数据表明，苯丙醇胺可能增强咖啡因的吸收或抑制其消除，这可以解释它们联合使用后报告的副作用增加。

The effects of caffeine and phenylpropanolamine are mediated through activation of the central and sympathetic nervous systems. Severe, life threatening, and occasionally fatal hypertensive reactions have been reported after their combined use. This study examined the possible pharmacokinetic interaction of phenylpropanolamine and caffeine. Sixteen normal subjects received combinations of caffeine, phenylpropanolamine, and placebo. In subjects receiving 400 mg caffeine plus 75 mg phenylpropanolamine, the mean (+ or - SEM) peak plasma caffeine concentration of 8.0 + or - 2.2 ug/mL was significantly greater than after 400 mg caffeine alone (2.1 + or - 0.3 ug/mL; t(24) = 2.4; p < 0.01). Physical side effects were more frequent after the phenylpropanolamine-caffeine combination than after either drug alone or after placebo. Greater increases in both systolic and diastolic blood pressures occurred after the combination than after either drug alone. These data indicate that phenylpropanolamine may enhance absorption or inhibit elimination of caffeine and may explain increased side effects reported after their combined use.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

这可能是由苯丙醇胺对心输出量的逆向作用产生的。阿托品对于心动过缓状态是有用的，利多卡因在存在室性异位活动时使用。心动过缓：硫酸阿托品……。室性心动过速或频繁的室性早搏：利多卡因……。如果利多卡因无反应，则使用普萘洛尔……。中枢神经系统毒性作用（激动、迷失方向、活动过度、幻觉、过度换气、呼吸急促）应进行对症治疗。癫痫发作：静脉注射地西泮……。

... This may be produced by reversing the effect of phenylpropanolamine on cardiac output. Atropine is useful for bradycardia states, and lidocaine in the presence of ventricular ectopic activity. Bradycardia: atropine sulfate ... . Ventricular tachycardia or frequent premature ventricular contractions: Lidocaine ... . If no response from lidocaine, then use propranolol ... . CNS toxic effects (agitation, disorientation, increased motor activity, hallucinations, hyperventilation, tachypnea) should be treated symptomatically. Seizures: intravenous diazepam ... .

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

非那丙胺口服吸收良好，血药浓度在一到两小时内达到峰值。该药物主要不经改变地排泄，主要的排泄途径是肾脏。由于非那丙胺是一种弱碱，其在酸性尿液中的排泄会增强。

Phenylpropanolamine is well absorbed orally, and the peak blood concentration is attained within one to two hours. ... The drug is principally excreted unchanged; the major route of excretion is renal. Since phenylpropanolamine is a weak base, elimination is enhanced in acid urine.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

苯丙醇胺从胃肠道容易被吸收。据报道，在口服25毫克盐酸苯丙醇胺后15-30分钟内发生鼻部充血缓解，并且似乎可以持续3小时。用于治疗效应的药物血浆浓度尚不清楚。在一项研究中，口服50毫克盐酸苯丙醇胺给空腹成人后，1-2小时内达到100 ng/mL的峰值血浆浓度，并且在给药后6小时内血浆浓度保持在60 ng/mL以上。在服用150毫克缓释制剂的药物后，3.5小时后达到300 ng/mL的峰值血浆浓度，苯丙醇胺浓度在12小时内保持在180 ng/mL以上。/盐酸苯丙醇胺/

Phenylpropanolamine is readily absorbed from the GI tract. Nasal decongestion reportedly occurs within 15-30 minutes after oral administration of 25 mg of phenylpropanolamine hydrochloride and appears to persist for 3 hours. Plasma concentrations of the drug required for a therapeutic effect are not known. In one study, peak plasma concentrations of 100 ng/mL were reached in 1-2 hours and concentrations remained greater than 60 ng/ml for 6 hours following oral administration of 50 mg of phenylpropanolamine hydrochloride to fasting adults. Following administration of 150 mg of an extended-release preparation of the drug, peak plasma concentrations of 300 ng/mL occurred after 3.5 hours and phenylpropanolamine concentrations remained greater than 180 ng/mL for 12 hours. /Phenylpropanolamine hydrochloride/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

动物研究表明，苯丙醇胺分布到各种组织和体液中，包括脑脊液和大脑。/盐酸苯丙醇胺/

Animal studies indicate that phenylpropanolamine is distributed into various tissues and fluids, including /cerebrospinal fluid/ and brain. /Phenylpropanolamine hydrochloride/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

盐酸苯丙醇胺从缓释胶囊和溶液中的生物利用度和药代动力学在12名18至36岁的男性受试者中进行研究，他们分别每天一次接受75毫克的胶囊或每天三次接受25毫克的溶液，持续4天。报告了胶囊和溶液的最大血浆浓度、达到最大浓度的时间以及浓度-时间曲线下的面积。从胶囊中药物的的平均一级吸收速率常数、消除半衰期和滞后时间分别为0.488 ngxhr/mL、5.84小时和0.394小时，而从溶液中分别为2.87 ngxhr/mL、3.73小时和0.325小时。胶囊较小的表观平均一级吸收速率常数和较长的消除半衰期是由于药物的缓慢释放，从而减慢了其吸收并产生了持续的血浆药物浓度。

The bioavailability and pharmacokinetics of phenylpropanolamine hydrochloride from a controlled release caplet and solution were studied in 12 male subjects, aged 18 to 36 yr, who received either a 75 mg caplet once daily or a 25 mg solution 3 times daily for 4 days. Maximum plasma concentrations, time to maximum concentration, and areas under the concentration-time curves are reported for both caplet and solution. The mean first order absorption rate constant, elimination half-life and lag time for the drug from the caplet were 0.488 ngxhr/mL, 5.84 hr, and 0.394 hr, respectively, and 2.87 ngxhr/mL, 3.73 hr, and 0.325 hr, respectively, from the solution. The smaller apparent mean first order absorption rate constant and longer elimination half-life from the caplet is due to the slow release of drug, thereby slowing its absorption and producing sustained plasma drug concentrations.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  alpha-(1-氨基乙基)-苯甲醇 在 对甲苯磺酸 作用下， 反应 8.0h， 生成 7-(2-Hydroxy-1-methyl-2-phenylethyl)-5,6-dimethyl-7H-pyrrolo<2,3-d>pyrimidin-4(3H)-on
  参考文献：
  名称：

  Pichler, Herbert; Folkers, Gerd; Roth, Hermann J., Liebigs Annalen der Chemie, 1986, # 9, p. 1485 - 1505

  摘要：

  DOI：
• 作为产物：
  描述：

  1-丙烯基苯 在 hydroxylamine triflate 、 水 、 iron(II) sulfate 作用下， 以 乙腈 为溶剂， 反应 16.0h， 以30%的产率得到alpha-(1-氨基乙基)-苯甲醇
  参考文献：
  名称：

  通过铁催化的C–H键胺化直接和实际合成伯胺

  摘要：

  芳烃的直接C–H胺化是简化功能分子的发现和制备的重要策略。在本文中，我们报道了一种操作简单的芳烃CH胺化反应，与大多数文献先例相反，该反应直接提供了合成通用的伯胺产品，而无需依赖于保护基团的操纵。廉价的硫酸铁（II）可作为转化的方便催化剂。该反应可耐受多种芳烃，包括结构复杂的药物。重要的是，芳烃底物在转化中用作限制性试剂。这种操作上简单的转变将大大加快药物和功能分子的发现。

  DOI：

  10.1021/acscatal.6b02576
• 作为试剂：
  描述：

  4-氯丙酸 、 苯硫酚 在 alpha-(1-氨基乙基)-苯甲醇 、 sodium hydroxide 作用下， 生成 5-oxo-2,3,4,5-tetrahydro-1-benzothiepin 1,1-dioxide 、 3,4-二氢-2H-苯并[B]硫杂卓-5-酮
  参考文献：
  名称：

  Analogues of N,1-diphenyl-4,5-dihydro-1H-[1]benzothiepino[5,4-c]pyrazole-3-carboxamide and N,1-diphenyl-4,5-dihydro-1H-[1]benzothiepino[5,4-c]pyrazole-3-carboxamide-6,6-dioxide: syntheses, characterization, antimicrobial, antituberculosis, and antitumor activity

  摘要：

  通过改变吡唑的活性部分（羧酰胺基团），合成了一系列 N,1-二苯基-4,5-二氢-1H-[1]苯并噻吩并[5,4-c]吡唑-3-甲酰胺（11a-m）和 N,1-二苯基-4,5-二氢-1H-[1]苯并噻吩并[5,4-c]吡唑-3-甲酰胺-6、通过改变吡唑的活性部分（羧酰胺基团）合成了 6-二氧化物（12a-m），并通过红外光谱、1H-NMR、13C-NMR、质谱数据和元素分析对其进行了表征。对所有化合物的抗菌和抗真菌活性进行了评估。化合物 11k 和 12k 对肺炎克雷伯氏菌和大肠埃希氏菌的活性高于氯霉素。与阿米卡星相比，化合物 11b、11c、11l、12b、12c 和 12l 在抑制大肠杆菌生长方面表现出更高的活性（MIC 3.125 毫克/毫升-1）。化合物 11k 和 12k 在抑制白色念珠菌生长方面的活性与克霉唑相当（MIC 3.125 毫克/毫升-1）。筛选了所有化合物对两种肿瘤细胞系（即人类结肠肿瘤细胞系（HCT116）和人类宫颈癌细胞系（HeLa））的细胞毒活性。大多数测试化合物都表现出了强大的抗肿瘤活性，尤其是化合物 11k 和 12k，它们在测试化合物中表现出了最高的活性，对 HeLa 细胞的 IC50 分别为 18 和 12 μM，对 HCT116 细胞的 IC50 分别为 16 和 10 μM。所有合成的化合物对结核杆菌（MTB）H37Rv 都显示出低到中等程度的抑制活性，而 11k 和 12k 与其他类似物相比，对结核杆菌更具活性，其 MIC 值分别为 8.2 和 7.8 μM。

  DOI：

  10.1039/c3ra23124k

文献信息

• 3-Aminocyclopentanecarboxamides as modulators of chemokine receptors
  申请人：Xue Chu-Biao

  公开号：US20060004018A1

  公开（公告）日：2006-01-05

  The present invention is directed to compounds of Formula I: which are modulators of chemokine receptors. The compounds of the invention, and compositions thereof, are useful in the treatment of diseases related to chemokine receptor expression and/or activity.

  本发明涉及以下式的化合物： 这些化合物是趋化因子受体的调节剂。本发明的化合物及其组合物在治疗与趋化因子受体表达和/或活性相关的疾病方面是有用的。
• CYCLOPROPYLAMINES AS LSD1 INHIBITORS
  申请人：Incyte Corporation

  公开号：US20150225379A1

  公开（公告）日：2015-08-13

  The present invention is directed to cyclopropylamine derivatives which are LSD1 inhibitors useful in the treatment of diseases such as cancer.

  本发明涉及环丙胺衍生物，这些衍生物是LSD1抑制剂，可用于治疗癌症等疾病。
• PHARMACEUTICAL COMPOUNDS AS INHIBITORS OF CELL PROLIFERATION AND THE USE THEREOF
  申请人：ANDERSON MARK B.

  公开号：US20100068197A1

  公开（公告）日：2010-03-18

  Disclosed are compounds of Formula I effective as cytotoxic agents. The compounds of this invention are useful in the treatment of a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

  揭示的是作为细胞毒性剂有效的I式化合物。本发明的化合物在治疗多种临床病况中是有用的，这些病况中发生异常细胞的不受控制的生长和扩散。
• [EN] NOVEL SMALL MOLECULE INHIBITORS OF TEAD TRANSCRIPTION FACTORS<br/>[FR] NOUVEAUX INHIBITEURS À PETITES MOLÉCULES DE FACTEURS DE TRANSCRIPTION TEAD
  申请人：MASSACHUSETTS GEN HOSPITAL

  公开号：WO2020190774A1

  公开（公告）日：2020-09-24

  The present disclosure compounds, as well as their compositions and methods of use. The compounds inhibit the activity of the TEAD transcription factor, and are useful in the treatment of diseases related to the activity of TEAD transcription factor including, e.g., cancer and other diseases.

  本公开涉及化合物及其组合物和使用方法。这些化合物抑制TEAD转录因子的活性，并可用于治疗与TEAD转录因子活性相关的疾病，例如癌症和其他疾病。
• MACROCYCLIC COMPOUNDS AND THEIR USE AS KINASE INHIBITORS
  申请人：Combs Andrew Paul

  公开号：US20090286778A1

  公开（公告）日：2009-11-19

  The present invention relates to macrocyclic compounds of Formula I: or pharmaceutically acceptable salts thereof or quaternary ammonium salts thereof wherein constituent members are provided hereinwith, as well as their compositions and methods of use, which are JAK/ALK inhibitors useful in the treatment of JAK/ALK-associated diseases including, for example, inflammatory and autoimmune disorders, as well as cancer.

  本发明涉及以下化学式I的大环化合物： 或其药用可接受盐或季铵盐，其中所述成员在此提供，并且它们的组成物和使用方法，这些JAK/ALK抑制剂在治疗JAK/ALK相关疾病中有用，例如炎症和自身免疫性疾病以及癌症。

表征谱图