左旋去甲麻黄碱 | 37577-28-9

• 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: 左旋去甲麻黄碱
• 中文别名: 苯基丙醇胺；消旋去甲麻黄碱；D-(+)-苯丙醇胺；(1S,2R)-(+)-去甲麻黄碱
• 英文名称: (1S,2R)-(+)-norphedrine
• 英文别名: (1S,2R)-(+)-norephedrine；(1S,2R)-2-amino-1-phenylpropan-1-ol；(+)-Norephedrine；PPA；phenylpropanolamine；(1R,2S)-(+)-norephedrine；D(+)-norephedrine；Norephedrine
• CAS: 37577-28-9；14838-15-4
• 化学式: C₉H₁₃NO
• 分子量: 151.208
• InChiKey: DLNKOYKMWOXYQA-VXNVDRBHSA-N

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

盐酸非诺特罗与吲哚美辛合用在一例病人中引起了严重的高血压；当单独使用其中任何一种药物时并未发生高血压。/盐酸非诺特罗/

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，可能会对给予普罗帕酮，一种β-肾上腺素能阻断剂有所反应。/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：

  左旋去甲麻黄碱 在 氯化亚砜 作用下， 反应 5.0h， 以74%的产率得到(1R,2R)-(-)-1-chloro-1-phenyl-2-propylamine hydrochloride
  参考文献：
  名称：

  再次探讨了麻黄碱的氯化反应。立体化学和官能团对反应机理的影响1

  摘要：

  分析了游离麻黄碱和伪麻黄碱与SOCl 2氯化反应的立体化学及其盐酸盐，草酰胺和磺酰胺。的自由和盐酸赤式异构体的氯化与C-1（S构型的100％反转发生Ñ 2机构）。赤型异构体的草酰胺和磺酰胺发生氯化反应，保留C-1构型（S N i机理）。所有苏式异构体及其衍生物的盐酸盐，草酰胺或磺酰胺中的氯化反应均得到相同比例的赤型（40％）和苏型（60％）（S N1机制）。用HCl处理DMSO中的盐酸氯脱氧麻黄碱和氯脱氧伪麻黄碱的异构体混合物会改变异构体比例，增加赤型异构体含量（65％）。如果该化合物事先被甲苯磺酸化或转化为酰胺，或者如果该化合物直接被SOCl 2氯化，则使用赤型乙醇胺可以有选择地到达赤型氯胺。

  DOI：

  10.1016/s0957-4166(98)00155-4
• 作为产物：
  描述：

  羟基(苯基)乙腈 在 咪唑 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 作用下， 以 乙醚 为溶剂， 反应 2.0h， 生成 左旋去甲麻黄碱
  参考文献：
  名称：

  Applications of Optically Active Aryl Cyanohydrins in the Synthesis of α-Hydroxy Aldehydes, α-Hydroxy Ketones and β-Hydroxy Amines

  摘要：

  从芳基醛中制备的高光学纯度氰基卤素可转化为 α-羟基醛、β-羟基酮和β-羟基胺，且无任何外消旋化现象，在新引入的立体中心处，赤式二对映异构体通常具有良好的立体选择性（90%）。

  DOI：

  10.1071/ch9902045
• 作为试剂：
  描述：

  2-bromoisovaleryl chloride 在 水 、 cesium fluoride 氯化镍二甲氧基乙烷 、 左旋去甲麻黄碱 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 为溶剂， 反应 16.0h， 生成 tert-butyl 2-phenylisovalerate
  参考文献：
  名称：

  镍/去氧麻黄碱络合物催化的活化和未活化仲烷基卤的Hiyama反应。

  摘要：

  DOI：

  10.1002/anie.200700440

文献信息

• [EN] AZA PYRIDONE ANALOGS USEFUL AS MELANIN CONCENTRATING HORMONE RECEPTOR-1 ANTAGONISTS<br/>[FR] ANALOGUES D'AZAPYRIDONE UTILES COMME ANTAGONISTES DU RÉCEPTEUR 1 DE L'HORMONE CONCENTRANT LA MÉLANINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2010104818A1

  公开（公告）日：2010-09-16

  MCHR1 antagonists are provided having the following Formula (I): A1 and A2 are independently C or N; E is C or N; Q1, Q2, and Q3 are independently C or N provided that at least one of Q1, Q2, and Q3 is N but not more than one of Q1, Q2, and Q3 is N; D1 is a bond, -CR8R9 X-, -XCR8R9-, -CHR8CHR9-, -CR10=CR10'-, -C≡C-, or 1,2-cyclopropyl; X is O, S or NR11; R1, R2, and R3 are independently selected from the group consisting of hydrogen, halogen, lower alkyl, lower cycloalkyl, -CF3, -OCF3, -OR12 and -SR12; G is O, S or -NR15; D2 is lower alkyl, lower cycloalkyl, lower alkylcycloalkyl, lower cycloalkylalkyl, lower cycloalkoxyalkyl or lower alkylcycloalkoxy or when G is NR15, G and D2 together may optionally form an azetidine, pyrrolidine or piperidine ring; Z1 and Z2 are independently hydrogen, lower alkyl, lower cycloalkyl, lower alkoxy, lower cycloalkoxy, halo, -CF3, -OCONR14R14', -CN, -CONR14R14', -SOR12, -SO2R12, -NR14COR14', -NR14CO2R14', -CO2R12, NR14SO2R12 or COR12; R5, R6, and R7 are independently selected from the group consisting of hydrogen lower alkyl, lower cycloalkyl, -CF3, -SR12, lower alkoxy, lower cycloalkoxy, -CN, -CONR14R14', SOR12, SO2R12, NR14COR14', NR14CO2R12, CO2R12, NR14SO2R12 and -COR12; R8, R9, R10, R10', R11 are independently hydrogen or lower alkyl; R12 is lower alkyl or lower cycloalkyl; R14 and R14' are independently H, lower alkyl, lower cycloalkyl or R14 and R14' together with the N to which they are attached form a ring having 4 to 7 atoms; and R15 is independently selected from the group consisting of hydrogen and lower alkyl. Such compounds are useful for the treatment of MCHR1 mediated diseases, such as obesity, diabetes, IBD, depression, and anxiety.

  MCHR1拮抗剂具有以下化学式（I）：A1和A2独立地为C或N；E为C或N；Q1、Q2和Q3独立地为C或N，但至少其中一个为N，但不超过一个为N；D1为键，-CR8R9 X-，-XCR8R9-，-CHR8CHR9-，-CR10=CR10'-，-C≡C-，或1,2-环丙基；X为O、S或NR11；R1、R2和R3独立地从氢、卤素、低烷基、低环烷基、-CF3、-OCF3、-OR12和-SR12组成的群体中选择；G为O、S或-NR15；D2为低烷基、低环烷基、低烷基环烷基、低环烷基烷基、低环烷氧基烷基或低烷基环烷氧基，或当G为NR15时，G和D2一起可以选择形成氮杂环丙烷、吡咯烷或哌啶环；Z1和Z2独立地为氢、低烷基、低环烷基、低烷氧基、低环烷氧基、卤素、-CF3、-OCONR14R14'、-CN、-CONR14R14'、-SOR12、-SO2R12、-NR14COR14'、-NR14CO2R14'、-CO2R12、NR14SO2R12或COR12；R5、R6和R7独立地从氢、低烷基、低环烷基、-CF3、-SR12、低烷氧基、低环烷氧基、-CN、-CONR14R14'、SOR12、SO2R12、NR14COR14'、NR14CO2R12、CO2R12、NR14SO2R12和-COR12组成的群体中选择；R8、R9、R10、R10'、R11独立地为氢或低烷基；R12为低烷基或低环烷基；R14和R14'独立地为H、低烷基、低环烷基或R14和R14'与其连接的N一起形成具有4至7个原子的环；R15独立地从氢和低烷基组成的群体中选择。这些化合物对于治疗MCHR1介导的疾病，如肥胖症、糖尿病、炎症性肠病、抑郁症和焦虑症非常有用。
• NOVEL GLUCOKINASE ACTIVATORS AND METHODS OF USING SAME
  申请人：Ryono Denis E.

  公开号：US20080009465A1

  公开（公告）日：2008-01-10

  Compounds are provided which are phosphonate and phosphinate activators and thus are useful in treating diabetes and related diseases and have the structure wherein is a heteroaryl ring; R 4 is —(CH 2 ) n -Z-(CH 2 ) m —PO(OR 7 )(OR 8 ), —(CH 2 ) n Z-(CH 2 ) m —PO(OR 7 )R g , —(CH 2 ) n -Z-(CH 2 ) m —OPO(OR 7 )R g , —(CH 2 ) n Z—(CH 2 ) m —OPO(R 9 )(R 10 ), or —(CH 2 ) n Z—(CH 2 ) m —PO(R 9 )(R 10 ); R 5 and R 6 are independently selected from H, alkyl and halogen; Y is R 7 (CH 2 ) s or is absent; and X, n, Z, m, R 4 , R 5 , R 6 , R 7 , and s are as defined herein; or a pharmaceutically acceptable salt thereof. A method for treating diabetes and related diseases employing the above compounds is also provided.

  提供了磷酸酯和磷酸酯激活剂，因此在治疗糖尿病和相关疾病方面非常有用，并具有以下结构： 其中 是杂环芳基环； R 4 为—(CH 2 ) n -Z-(CH 2 ) m —PO(OR 7 )(OR 8 )、—(CH 2 ) n Z-(CH 2 ) m —PO(OR 7 )R g 、—(CH 2 ) n -Z-(CH 2 ) m —OPO(OR 7 )R g 、—(CH 2 ) n Z—(CH 2 ) m —OPO(R 9 )(R 10) 或—(CH 2 ) n Z—(CH 2 ) m —PO(R 9 )(R 10) ； R 5 和R 6 分别选择自H、烷基和卤素； Y为R 7 (CH 2 ) s 或不存在；以及 X、n、Z、m、R 4 、R 5 、R 6 、R 7 和s如本文所定义；或其药用盐。 还提供了一种利用上述化合物治疗糖尿病和相关疾病的方法。
• [EN] METHYL OXAZOLE OREXIN RECEPTOR ANTAGONISTS<br/>[FR] MÉTHYLOXAZOLES ANTAGONISTES DU RÉCEPTEUR DE L'OREXINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2016089721A1

  公开（公告）日：2016-06-09

  The present invention is directed to methyl oxazole compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.

  本发明涉及甲基噁唑化合物，其为促进睡眠的受体拮抗剂。本发明还涉及所述化合物在潜在治疗或预防涉及促进睡眠的神经和精神疾病和疾病中的用途。本发明还涉及包含这些化合物的组合物。本发明还涉及这些组合物在潜在预防或治疗涉及促进睡眠的疾病中的用途。
• 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。
• CYTOTOXIC PEPTIDES AND ANTIBODY DRUG CONJUGATES THEREOF
  申请人：PFIZER INC.

  公开号：US20130129753A1

  公开（公告）日：2013-05-23

  The present invention is directed to cytotoxic pentapeptides, to antibody drug conjugates thereof, and to methods for using the same to treat cancer.

  本发明涉及细胞毒性五肽，其抗体药物偶联物，以及使用它们治疗癌症的方法。

表征谱图