去甲麻黄碱 | 492-41-1

• 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: 去甲麻黄碱
• 中文别名: L-降麻黄碱；(-)-降麻黄碱
• 英文名称: (1R,2S)-norephedrine
• 英文别名: (-)-norephedrine；Phenylpropanolamine；(1R,2S)-2-amino-1-phenylpropan-1-ol
• CAS: 492-41-1
• 化学式: C₉H₁₃NO
• 分子量: 151.208
• InChiKey: DLNKOYKMWOXYQA-CBAPKCEASA-N

物化性质

• 稳定性/保质期：

  按规格使用和贮存，不会发生分解，避免与氧化物接触。

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

肝脏的

Hepatic

来源:DrugBank

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，咖啡因的平均（±SEM）峰值血浆浓度为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）。物理副作用在苯丙醇胺-咖啡因组合后比单独使用任一药物或安慰剂后更常见。组合使用后的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

• 吸收

生物利用度降低（约38%），因为胃肠道中的单胺氧化酶在胃和肝脏中进行首次通过代谢。

Reduced bioavailability (about 38%) from gastrointestinal tract because of first pass metabolism by monoamine oxidase in the stomach and liver.

来源:DrugBank

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

盐酸去氧肾上腺素很容易从胃肠道吸收。据报道，在口服25毫克盐酸去氧肾上腺素后15-30分钟内即可发生鼻部充血缓解，并且这种效果似乎可以持续3小时。对于治疗所需药物的血药浓度尚不清楚。在一项研究中，空腹成人口服50毫克盐酸去氧肾上腺素后，血药浓度在1-2小时内达到峰值100纳克/毫升，并且在给药后6小时内血药浓度保持在60纳克/毫升以上。在服用150毫克缓释制剂的药物后，血药浓度在3.5小时后达到峰值300纳克/毫升，去氧肾上腺素浓度在12小时内保持在180纳克/毫升以上。/盐酸去氧肾上腺素/

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)

安全信息

• 储存条件：
  应将产品存放在2-8°C的环境下，并密封保存。建议将其置于通风、干燥的地方。

制备方法与用途

合成制备方法

暂无相关信息。

用途

暂无相关信息。

反应信息

• 作为反应物：
  描述：

  去甲麻黄碱 在 五氯化磷 作用下， 以 氯仿 为溶剂， 反应 1.0h， 以75%的产率得到(1S,2S)-(+)-1-chloro-1-phenyl-2-propylamine hydrochloride
  参考文献：
  名称：

  （2 R，3 S）-（-）-2-苯基-3-甲基氮丙啶的合成

  摘要：

  我们报告的氮丙啶的全合成3，在的碳原子的（1个羟基涉及双瓦尔登翻转两步的方法进行[R，2小号） -降麻黄碱，（ - ） - 1，其被用作，起始材料。化合物3首次以固体形式获得，因此可以确定其明确的X射线结构。

  DOI：

  10.1016/s0957-4166(97)00271-1
• 作为产物：
  描述：

  (4S,5R)-4-methyl-5-phenyl-[1,2,3]oxathiazolidine 2,2-dioxide 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以71.5%的产率得到去甲麻黄碱
  参考文献：
  名称：

  Stereoselective Synthesis of Norephedrine and Norpseudoephedrine by Using Asymmetric Transfer Hydrogenation Accompanied by Dynamic Kinetic Resolution

  摘要：

  Each of the enantiomers of both norephedrine and norpseudoephedrine were stereoselectively prepared from the common, prochiral cyclic sulfamidate imine of racemic 1-hydroxy-1-phenyl-propan-2-one by employing asymmetric transfer hydrogenation (ATH) catalyzed by the well-defined chiral Rh-complexes, (S,S)- or (R,R)-Cp*RhCl(TsDPEN), and HCO2H/Et3N as the hydrogen source. The ATH processes are carried out under mild conditions (rt, 15 min) and are accompanied by dynamic kinetic resolution.

  DOI：

  10.1021/jo300867y
• 作为试剂：
  描述：

  2-呋喃基苯基酮 在 去甲麻黄碱 、 硼烷 、 盐酸羟胺 、 sodium acetate 、 sodium hydride 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 63.0h， 生成 (R)-(furan-2-yl)(phenyl)methanamine
  参考文献：
  名称：

  呋喃-2-基胺和氨基酸的对映体的新型对映选择性合成

  摘要：

  描述了呋喃-2-基胺和氨基酸的一种新的对映选择性合成，其中关键步骤是恶唑硼烷催化的O-苄基（E）-和（Z）-呋喃-2-基酮肟的对映选择性还原。相应的手性胺。呋喃-2-基胺的手性通过的几何异构体的合适的选择完全控制ø -苄基肟。呋喃环的氧化以高产率提供了氨基酸。

  DOI：

  10.1002/hlca.200390022

文献信息

• 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] COMPOUNDS COMPRISING CLEAVABLE LINKER AND USES THEREOF<br/>[FR] COMPOSÉS COMPRENANT UN LIEUR CLIVABLE ET LEURS UTILISATIONS
  申请人：INTOCELL INC

  公开号：WO2019008441A1

  公开（公告）日：2019-01-10

  Provided are a compound including a cleavable linker, a use thereof, and an intermediate compound for preparing the same, and more particularly, the compound including a cleavable linker of the present invention may include an active agent (for example, a drug, a toxin, a ligand, a probe for detection, etc.) having a specific function or activity, a SO2 functional group which is capable of selectively releasing the active agent, and a functional group which triggers a chemical reaction, a physicochemical reaction and/or a biological reaction by external stimulation, and may further include a ligand (for example, oligopeptide, polypeptide, antibody, etc.) having binding specificity for a desired target receptor.

  提供了一种包括可切割连接物的化合物，其用途，以及用于制备该化合物的中间体化合物，更具体地，本发明的包括可切割连接物的化合物可能包括具有特定功能或活性的活性剂（例如，药物，毒素，配体，用于检测的探针等），能够选择性释放活性剂的SO2官能团，以及通过外部刺激触发化学反应，物理化学反应和/或生物反应的官能团，并且还可以包括具有与所需靶受体结合特异性的配体（例如，寡肽，多肽，抗体等）。
• Highly enantioselective carbonyl reduction with borane catalyzed by chiral spiroborate esters derived from chiral beta-aminoalcohols
  申请人：Ortiz-Marciales Margarita

  公开号：US20080200672A1

  公开（公告）日：2008-08-21

  Novel spiroborate esters derived from non-recemic 1,2-amino alcohols were examined as chiral catalyst in the borane reduction of acetophenone and other aromatic ketones at room temperature. The optically active alcohols were obtained in excellent chemical yields and up to 99% ee with less than 10% catalyst.

  从非手性1,2-氨基醇衍生的新型螺环硼酸酯作为手性催化剂在室温下用于苯乙酮和其他芳香酮的硼氢化还原反应。光学活性醇以极高的化学产率获得，ee值高达99%，催化剂用量不到10%。
• FLAP MODULATORS
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：US20150259357A1

  公开（公告）日：2015-09-17

  The present invention relates to compounds of Formula (I), or a form thereof, wherein ring A, R 1 , R 2 , R 3 , R 3 ′, L, W, and V are as defined herein, useful as FLAP modulators. The invention also relates to pharmaceutical compositions comprising compounds of Formula (I). Methods of making and using the compounds of Formula (I) are also within the scope of the invention

  本发明涉及式（I）的化合物，或其形式，其中环A，R1，R2，R3，R3'，L，W和V如本文所定义，可用作FLAP调节剂。该发明还涉及包含式（I）化合物的药物组合物。制备和使用式（I）化合物的方法也属于本发明的范围。
• New Chiral Derivatizing Agents: Convenient Determination of Absolute Configurations of Free Amino Acids by ¹H NMR
  作者：Michio Kurosu、Kai Li

  DOI：10.1021/ol8028719

  日期：2009.2.19

  The chiral carbonate reagents 5 allow for the direct and unambiguous determination of the absolute configurations of a wide range of free amino acids using 1H NMR. By using a ∼3:1 mixture of (S)-5 and (R)-5, absolute configurations of the corresponding carbamates are determined by only analyzing the nitrogen protons.

  手性碳酸酯试剂5允许使用1 H NMR直接和明确地确定各种游离氨基酸的绝对构型。通过使用〜（S）-5和（R）-5的〜3：1混合物，仅通过分析氮质子即可确定相应氨基甲酸酯的绝对构型。

表征谱图