左旋甲基苯丙胺 | 33817-09-3

• 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: 左旋甲基苯丙胺
• 中文别名: (-)-2-[甲基氨基]-1-苯丙烷；1-苯基-2-甲氨基丙烷；冰毒；(-)-去氧麻黄碱；脱氧麻黄碱；N-甲安非他命；左甲非他明
• 英文名称: (R)-2-methylamino-1-phenylpropane
• 英文别名: l-methamphetamine；d-methamphetamine；Levmetamfetamine；(2R)-N-methyl-1-phenylpropan-2-amine
• CAS: 33817-09-3
• 化学式: C₁₀H₁₅N
• 分子量: 149.236
• InChiKey: MYWUZJCMWCOHBA-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

ADMET

代谢

Methamphetamine is a known human metabolite of selegiline.

Methamphetamine is a known human metabolite of selegiline.

来源:NORMAN Suspect List Exchange

毒理性

• 在妊娠和哺乳期间的影响

◉ 哺乳期使用概述：由于缺乏将甲基苯丙胺作为治疗药物在哺乳期使用的已发表经验，可能更倾向于选择其他药物，特别是在哺乳新生儿或早产儿时。一位专家建议，不应在哺乳母亲中使用苯丙胺类药物进行药物治疗。 甲基苯丙胺不应作为哺乳期母亲的娱乐性药物使用，因为它可能会损害她们的判断力和照顾儿童的能力。在哺乳期母亲滥用甲基苯丙胺后，甲基苯丙胺及其代谢物苯丙胺可以在母乳和婴儿血清中检测到。然而，由于在给哺乳期母亲服用娱乐性甲基苯丙胺方面存在伦理考虑，这些数据来自随机收集而不是控制研究。其他需要考虑的因素包括哺乳婴儿可能出现阳性尿检的可能性，这可能会产生法律影响，以及街头毒品可能含有其他有害杂质的可能性。通常不鼓励积极滥用苯丙胺类药物的母亲进行哺乳。在哺乳期滥用甲基苯丙胺的母亲中，建议在最后一次使用后48至100小时不进行哺乳，尽管许多母亲在最后一次使用后平均72小时母乳中就检测不到甲基苯丙胺。有人建议，在母亲尿检苯丙胺阴性24小时后，可以恢复哺乳。 ◉ 对哺乳婴儿的影响：一名两个月大的婴儿，其母亲通过鼻腔吸入娱乐性街头甲基苯丙胺，并在少量哺乳和摄入120至180毫升配方奶后8小时死亡。尸检时婴儿血清中甲基苯丙胺浓度为39微克/升。尽管婴儿的母亲因在哺乳期使用甲基苯丙胺而被判定为危害儿童安全，但由于婴儿血清中甲基苯丙胺浓度较低以及母亲据称哺乳次数极少，甲基苯丙胺在婴儿死亡中的作用受到了质疑。 南澳大利亚政府病理学家报告了一名与母亲同睡的哺乳婴儿的死亡。尸检时在婴儿体内发现了“显著”浓度的甲基苯丙胺，认为母乳中的药物可能是导致死亡的一个潜在因素。这些作者还报告说，在之前12个月以下婴儿的死亡案例中，检测到的甲基苯丙胺及其代谢物苯丙胺可能部分是通过母乳获得的。新西兰政府病理学家也确认了他们国家类似的发现。 ◉ 对泌乳和母乳的影响：给6名受试者（4名男性和2名女性）单次口服0.2毫克/公斤，最大不超过17.5毫克的d-甲基苯丙胺。在给药后300分钟内，血清催乳素浓度没有变化。 在两篇由同一作者撰写的论文中，研究了20名具有正常生理性高催乳素血症的妇女，这些妇女在分娩后第2或第3天进行研究。其中8人接受了7.5毫克静脉注射右旋苯丙胺，6人接受了15毫克静脉注射，6人作为对照组接受了静脉注射生理盐水。7.5毫克剂量使血清催乳素下降了25至32%，与对照组相比差异无统计学意义。15毫克剂量在输注后一段时间显著降低了血清催乳素30至37%。没有提出对乳汁产量的评估。作者还引用了另一项研究的数据，显示20毫克口服剂量的右旋苯丙胺使产后妇女的血清催乳素持续下降了40%。 一项研究比较了31名甲基苯丙胺依赖者与23名非依赖者。甲基苯丙胺依赖者在戒断后第2天和第30天的血清催乳素浓度升高。这种升高在女性中比男性更明显。在已建立泌乳的母亲中，母体催乳素水平可能不会影响她的哺乳能力。 在一项回顾性澳大利亚研究中，使用静脉注射苯丙胺的孕妇在出院时哺乳新生儿的可能性低于滥用其他药物的孕妇（27%对42%）。这种差异的原因尚未确定。 一项前瞻性、多中心研究跟踪了在产前使用甲基苯丙胺的母亲（n = 204）与未使用的母亲（n = 208）。暴露于甲基苯丙胺的婴儿表现出吸吮力差、过度吸吮和更多的颤抖，与对照组相比。使用甲基苯丙胺的母亲在出院时哺乳婴儿的可能性低于未使用甲基苯丙胺的母亲（38%对76%）。

◉ Summary of Use during Lactation:Because there is no published experience with methamphetamine as a therapeutic agent during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. One expert recommends that amphetamines not be used therapeutically in nursing mothers. Methamphetamine should not be used as a recreational drug by nursing mothers because it may impair their judgment and childcare abilities. Methamphetamine and its metabolite, amphetamine, are detectable in breastmilk and infant's serum after abuse of methamphetamine by nursing mothers. However, these data are from random collections rather than controlled studies because of ethical considerations in administering recreational methamphetamine to nursing mothers. Other factors to consider are the possibility of positive urine tests in breastfed infants which might have legal implications, and the possibility of other harmful contaminants in street drugs. Breastfeeding is generally discouraged in mothers who are actively abusing amphetamines. In mothers who abuse methamphetamine while nursing, withholding breastfeeding for 48 to 100 hours after the maternal use been recommended, although in many mothers methamphetamine is undetectable in breastmilk after an average of 72 hours from the last use. It has been suggested that breastfeeding can be reinstated 24 hours after a negative maternal urine screen for amphetamines. ◉ Effects in Breastfed Infants:A 2-month-old infant whose mother used illicit street methamphetamine recreationally by nasal inhalation was found dead 8 hours after a small amount of breastfeeding and ingestion of 120 to 180 mL of formula. The infant's serum methamphetamine concentration on autopsy was 39 mcg/L. Although the infant's mother was convicted of child endangerment for the use of methamphetamine during breastfeeding, the role that methamphetamine played in the infant's death has been questioned because of the low infant serum methamphetamine concentration and the mother's alleged minimal breastfeeding. South Australian government pathologists reported the death of a breastfed infant who was co-sleeping with its mother. Methamphetamine was found in a “significant” concentration in the infant on autopsy and the drug in breastmilk was thought to be potentially contributory to the death. These authors also reported that in prior deaths of infants under 12 months of age, detectable methamphetamine and its metabolite, amphetamine, may have been partially obtained via breastmilk. Pathologists from the New Zealand government confirmed similar findings in their country. ◉ Effects on Lactation and Breastmilk:A single oral dose of 0.2 mg/kg to a maximum of 17.5 mg of d-methamphetamine was given to 6 subjects (4 male and 2 female). Serum prolactin concentrations were unchanged over a period of 300 minutes after the dose. In 2 papers by the same authors, 20 women with normal physiologic hyperprolactinemia were studied on days 2 or 3 postpartum. Eight received dextroamphetamine 7.5 mg intravenously, 6 received 15 mg intravenously and 6 who served as controls received intravenous saline. The 7.5 mg dose reduced serum prolactin by 25 to 32% compared to control, but the difference was not statistically significant. The 15 mg dose significantly decreased serum prolactin by 30 to 37% at times after the infusion. No assessment of milk production was presented. The authors also quoted data from another study showing that a 20 mg oral dose of dextroamphetamine produced a sustained suppression of serum prolactin by 40% in postpartum women. A study compared 31 methamphetamine-dependent subject to 23 non-dependent subjects. The serum prolactin concentrations in the methamphetamine-dependent subjects were elevated at days 2 and 30 of abstinence. The elevation was greater in women than in men. The maternal prolactin level in a mother with established lactation may not affect her ability to breastfeed. In a retrospective Australian study, mothers who used intravenous amphetamines during pregnancy were less likely to be breastfeeding their newborn infants at discharge than mothers who abused other drugs (27% vs 42%). The cause of this difference was not determined. A prospective, multicenter study followed mothers who used methamphetamine prenatally (n = 204) to those who did not (n = 208). Infants exposed to methamphetamine exhibited poor suck, excessive suck and more jitteriness compared to nonexposed infants. Mothers who used methamphetamine were less likely to breastfeed their infants (38%) at hospital discharge than those who did not use methamphetamine (76%).

来源:Drugs and Lactation Database (LactMed)

反应信息

• 作为反应物：
  描述：

  左旋甲基苯丙胺 在 溶剂黄146 、 铂 作用下， 生成 (R)-2-methylamino-1-cyclohexyl-propane
  参考文献：
  名称：

  制备一些伯和仲的β-环己基烷基胺。

  摘要：

  DOI：

  10.1021/ja01197a039
• 作为产物：
  描述：

  盐酸右旋麻黄碱 在 氯化亚砜 、 palladium on barium sulfate 、 氢气 、 sodium acetate 作用下， 生成 左旋甲基苯丙胺
  参考文献：
  名称：

  液相色谱法测定由麻黄碱和伪麻黄碱制得的甲基苯丙胺对映体组成。

  摘要：

  DOI：

  10.1021/ac00121a011
• 作为试剂：
  描述：

  扁桃酸 在 左旋甲基苯丙胺 作用下， 生成 (S)-(+)-扁桃酸
  参考文献：
  名称：

  Continuous nicardipine infusion to control blood pressure after evacuation of acute cerebral hemorrhage

  摘要：

  Purpose: To explore the long-term effects of the calcium antagonist, nicardipine, on cerebral hemodynamic in patients with acute cerebral hemorrhage, we investigated the effects of nicardipine infusion on intracranial pressure (ICP), middle cerebral arterial blood flow velocity (Vmca), and computed tomographical (CT) findings of bleeding and edema.Methods: Twenty-two patients with acute cerebral hemorrhage were infused with nicardipine for > 72 hr to decrease blood pressure. Blood pressure, heart rate, conscious level, Vmca, pulsatility index (PI, using transcranial Doppler), ICP, cerebral perfusion pressure (CPP) and platelet counts were monitored. CT examination was also performed to detect the changes of bleeding (hematoma) and/or brain edema.Results: Blood pressure decreased (20 to 30% from control, P < 0.05) without any changes in heart rate. Platelet count did not change neither did Vmca and PI change on either the intact or injured side. The ICP decreased 24 hr after the end of infusion from 30 +/- 12 mmHg to 20 +/- 9 mmHg (P = 0.036) but was still higher than normal. The CPP decreased at 24 hr (75 +/- 14 mmHg, P = 0.026) and 72 hr (73 +/- 15 mmHg, P = 0.024) from the baseline (99 +/- 17 mmHg). Conscious level improved but not significantly and CT findings did not show any exacerbation in bleeding or edema.Conclusion: In patients with acute cerebral hemorrhage, nicardipine infusion to decrease blood pressure by 20 to 30% had no effect on Vmca, ICP cerebral bleeding and edema, but decreased CPP.

  DOI：

  10.1007/bf03019868

文献信息

• [EN] METHODS AND COMPOSITIONS FOR SUBSTANCE USE DISORDER VACCINE FORMULATIONS AND USES THEREOF<br/>[FR] MÉTHODES ET COMPOSITIONS DESTINÉES À DES FORMULATIONS VACCINALES CONTRE DES TROUBLES LIÉS À UNE SUBSTANCE, ET LEURS UTILISATIONS
  申请人：MOLECULAR EXPRESS INC

  公开号：WO2018231706A1

  公开（公告）日：2018-12-20

  The present invention relates to vaccine compositions for treatment of substance use disorders, methods for the manufacture thereof, and methods for the use thereof to treat an animal. These compositions comprise a hapten conjugated via a linker to a protein scaffold and mixed with a particulate carrier and at least one immunostimulatory adjuvant molecule.

  本发明涉及用于治疗物质使用障碍的疫苗组合物，其制造方法以及用于治疗动物的方法。这些组合物包括通过连接剂与蛋白质支架结合的半抗原，并与颗粒载体和至少一种免疫刺激性佐剂分子混合。
• Evaluation of the Edman degradation product of vancomycin bonded to core-shell particles as a new HPLC chiral stationary phase
  作者：Garrett Hellinghausen、Diego A. Lopez、Jauh T. Lee、Yadi Wang、Choyce A. Weatherly、Abiud E. Portillo、Alain Berthod、Daniel W. Armstrong

  DOI：10.1002/chir.22985

  日期：2018.9

  macrocyclic glycopeptide‐based chiral stationary phase (CSP), prepared via Edman degradation of vancomycin, was evaluated as a chiral selector for the first time. Its applicability was compared with other macrocyclic glycopeptide‐based CSPs: TeicoShell and VancoShell. In addition, another modified macrocyclic glycopeptide‐based CSP, NicoShell, was further examined. Initial evaluation was focused on the complementary

  通过对万古霉素的Edman降解制备的修饰的基于大环糖肽的手性固定相（CSP）被首次评估为手性选择剂。将其适用性与其他基于大环糖肽的CSP（TeicoShell和VancoShell）进行了比较。此外，还进一步检查了另一种基于大环糖肽的修饰CSP NicoShell。最初的评估集中在与这些糖肽的互补行为上。根据以前的工作，使用了一种筛选方法，用于对50种手性化合物的对映体分离，其中包括氨基酸，农药，兴奋剂和多种药物。使用表面多孔（核-壳）颗粒载体可实现快速有效的手性分离。总体，万古霉素埃德曼降解产物（EDP）与TeicoShell类似，在极性离子模式下对酸性化合物具有高对映选择性。使用液相色谱-质谱联用EDP同时分离5种外消旋脯氨酸的对映异构体，时间约为3分钟。其他亮点包括同时用VancoShell液相色谱分离rac-amphetamine和rac-methamphetamine，用Nico
• [EN] CHEMICAL COMPOUNDS<br/>[FR] COMPOSÉS CHIMIQUES
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2010059658A1

  公开（公告）日：2010-05-27

  The invention is directed to 6-(4-pyιϊmidinyl)-1 H-indazole derivatives. Specifically, the invention is directed to compounds according to Formula (I) wherein R1 - R4 are defined herein. The compounds of the invention are inhibitors of PDK1 and can be useful in the treatment of immune and metabolic diseases and disorders characterized by constitutively activated ACG kinases such as cancer and more specifically cancers of the breast, colon, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  这项发明涉及6-(4-吡咯嗪基)-1 H-吲唑衍生物。具体而言，该发明涉及符合式(I)的化合物，其中R1-R4在此处被定义。该发明的化合物是PDK1的抑制剂，可用于治疗由于恒定激活的ACG激酶所特征化的免疫和代谢性疾病和紊乱，如癌症，更具体地说是乳腺癌、结肠癌和肺癌。因此，该发明进一步涉及包括该发明化合物的药物组合物。该发明还进一步涉及使用该发明化合物或包括该发明化合物的药物组合物来抑制PDK1活性和治疗相关疾病的方法。
• Chiral Separation of Cathinone and Amphetamine Derivatives by HPLC/UV Using Sulfated ß-Cyclodextrin as Chiral Mobile Phase Additive
  作者：Magdalena Taschwer、Yvonne Seidl、Stefan Mohr、Martin G. Schmid

  DOI：10.1002/chir.22341

  日期：2014.8

  this research work was to develop an inexpensive method for the chiral separation of cathinones and amphetamines. This should help to discover if the substances are sold as racemic mixtures and give further information about their quality as well as their origin. Chiral separation of a set of 6 amphetamine and 25 cathinone derivatives, mainly purchased from various Internet shops, is presented. A LiChrospher

  在过去的几年中，新的合法和非法高价的确定已成为警察和检察机关的巨大挑战。在分析方面，只有几种分析方法可用于识别这些新物质。而且，许多这些休闲药物是手性的，并且认为对映异构体的药理效力不同。由于非对映选择性合成更容易，更便宜，因此它们主要以外消旋混合物的形式出售。这项研究工作的目的是开发一种廉价的方法，用于手性分离卡西酮和苯丙胺。这应该有助于发现这些物质是否以外消旋混合物的形式出售，并提供有关其质量及其来源的更多信息。一组6种苯丙胺和25种卡西酮衍生物的手性分离，介绍了主要从各种互联网商店购买的产品。固定相使用250 x 4 mm，5 µm的LiChrospher 100 RP-18e。手性流动相由甲醇，水和硫酸化的β-环糊精组成。使用UV检测在反相模式下在等度条件下进行测量。使用两种物质类别的四种模型化合物来优化流动相。在最终条件下（甲醇：水2.5：97.5 + 2％硫酸化的β-环糊精），
• Stereoisomers of allenic amines as inactivators of monoamine oxidase type B. Stereochemical probes of the active site
  作者：Roger A. Smith、Robert L. White、Allen Krantz

  DOI：10.1021/jm00403a012

  日期：1988.8

  The kinetics of inactivation of mitochondrial monoamine oxidase type B (MAO-B) by a series of 18 stereoisomers of tertiary alpha-allenic amines have been investigated in detail. The chirality of the allene group in N-methyl-N-aralkylpenta-2,3-dienamines was found to have a profound effect on the inactivation rate, with the (R)-allenes being up to 200-fold more potent than their (S)-allenic counterparts

  已详细研究了一系列18种叔α-烯丙胺立体异构体对线粒体单胺氧化酶B型（MAO-B）的灭活动力学。发现N-甲基-N-芳烷基戊2,3-二烯胺中丙二烯基的手性对失活速率有深远影响，（R）-丙二烯的效价比其（ S）-allenic同行。N-苯乙基或N-α-取代的芳烷基取代基的存在严重损害了（S）-烯烯使MAO失活的能力。（R，R）-和（S，S）-N-甲基-N-（1,2,3,4-四氢-1-萘基）-penta-2的烯丙基和芳烷基中的相反手性， 3-二烯胺+ ++导致灭活速率的差异超过3个数量级。用一系列可逆的芳烷基胺抑制剂进一步检查了MAO-B的立体选择性。因此，确定（R）-1,2,3,4-四氢-1-萘胺的效价是其对映体的150倍。

表征谱图