(anti)-2-(methylamino)-1-(p-tolyl)propan-1-ol

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (anti)-2-(methylamino)-1-(p-tolyl)propan-1-ol
• 英文别名: (1R,2S)-dihydromephedrone；(1R,2S)-2-(methylamino)-1-(4-methylphenyl)propan-1-ol
• 化学式: C₁₁H₁₇NO
• 分子量: 179.262
• InChiKey: DUESQFQLBNOCIT-ONGXEEELSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (anti)-2-(methylamino)-1-(p-tolyl)propan-1-ol 在 盐酸 作用下， 以 乙醚 为溶剂， 以50%的产率得到(anti)-2-(methylamino)-1-(p-tolyl)propan-1-ol hydrochloride
  参考文献：
  名称：

  Phase I metabolites of mephedrone display biological activity as substrates at monoamine transporters

  摘要：

  Background and Purpose4‐Methyl‐N‐methylcathinone (mephedrone) is a synthetic stimulant that acts as a substrate‐type releaser at transporters for dopamine (DAT), noradrenaline (NET) and 5‐HT (SERT). Upon systemic administration, mephedrone is metabolized to several phase I compounds: the N‐demethylated metabolite, 4‐methylcathinone (nor‐mephedrone); the ring‐hydroxylated metabolite, 4‐hydroxytolylmephedrone (4‐OH‐mephedrone); and the reduced keto‐metabolite, dihydromephedrone.Experimental ApproachWe used in vitro assays to compare the effects of mephedrone and synthetically prepared metabolites on transporter‐mediated uptake and release in HEK293 cells expressing human monoamine transporters and in rat brain synaptosomes. In vivo microdialysis was employed to examine the effects of i.v. metabolite injection (1 and 3 mg·kg−1) on extracellular dopamine and 5‐HT levels in rat nucleus accumbens.Key ResultsIn cells expressing transporters, mephedrone and its metabolites inhibited uptake, although dihydromephedrone was weak overall. In cells and synaptosomes, nor‐mephedrone and 4‐OH‐mephedrone served as transportable substrates, inducing release via monoamine transporters. When administered to rats, mephedrone and nor‐mephedrone produced elevations in extracellular dopamine and 5‐HT, whereas 4‐OH‐mephedrone did not. Mephedrone and nor‐mephedrone, but not 4‐OH‐mephedrone, induced locomotor activity.Conclusions and ImplicationsOur results demonstrate that phase I metabolites of mephedrone are transporter substrates (i.e. releasers) at DAT, NET and SERT, but dihydromephedrone is weak in this regard. When administered in vivo, nor‐mephedrone increases extracellular dopamine and 5‐HT in the brain whereas 4‐OH‐mephedrone does not, suggesting the latter metabolite does not penetrate the blood–brain barrier. Future studies should examine the pharmacokinetics of nor‐mephedrone to determine its possible contribution to the in vivo effects produced by mephedrone.

  DOI：

  10.1111/bph.13547
• 作为产物：
  描述：

  (S)-tert-butyl (1-oxo-1-(p-tolyl)propan-2-yl)carbamate 在 lithium aluminium tetrahydride 、 zinc tetrafluoroborate 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 5.5h， 生成 (anti)-2-(methylamino)-1-(p-tolyl)propan-1-ol
  参考文献：
  名称：

  Phase I metabolites of mephedrone display biological activity as substrates at monoamine transporters

  摘要：

  Background and Purpose4‐Methyl‐N‐methylcathinone (mephedrone) is a synthetic stimulant that acts as a substrate‐type releaser at transporters for dopamine (DAT), noradrenaline (NET) and 5‐HT (SERT). Upon systemic administration, mephedrone is metabolized to several phase I compounds: the N‐demethylated metabolite, 4‐methylcathinone (nor‐mephedrone); the ring‐hydroxylated metabolite, 4‐hydroxytolylmephedrone (4‐OH‐mephedrone); and the reduced keto‐metabolite, dihydromephedrone.Experimental ApproachWe used in vitro assays to compare the effects of mephedrone and synthetically prepared metabolites on transporter‐mediated uptake and release in HEK293 cells expressing human monoamine transporters and in rat brain synaptosomes. In vivo microdialysis was employed to examine the effects of i.v. metabolite injection (1 and 3 mg·kg−1) on extracellular dopamine and 5‐HT levels in rat nucleus accumbens.Key ResultsIn cells expressing transporters, mephedrone and its metabolites inhibited uptake, although dihydromephedrone was weak overall. In cells and synaptosomes, nor‐mephedrone and 4‐OH‐mephedrone served as transportable substrates, inducing release via monoamine transporters. When administered to rats, mephedrone and nor‐mephedrone produced elevations in extracellular dopamine and 5‐HT, whereas 4‐OH‐mephedrone did not. Mephedrone and nor‐mephedrone, but not 4‐OH‐mephedrone, induced locomotor activity.Conclusions and ImplicationsOur results demonstrate that phase I metabolites of mephedrone are transporter substrates (i.e. releasers) at DAT, NET and SERT, but dihydromephedrone is weak in this regard. When administered in vivo, nor‐mephedrone increases extracellular dopamine and 5‐HT in the brain whereas 4‐OH‐mephedrone does not, suggesting the latter metabolite does not penetrate the blood–brain barrier. Future studies should examine the pharmacokinetics of nor‐mephedrone to determine its possible contribution to the in vivo effects produced by mephedrone.

  DOI：

  10.1111/bph.13547

文献信息

• [EN] BORONIC ACID DERIVATIVES AND SYNTHESIS, POLYMORPHIC FORMS, AND THERAPEUTIC USES THEREOF<br/>[FR] DÉRIVÉS D'ACIDE BORONIQUE ET SYNTHÈSE, FORMES POLYMORPHES ET UTILISATIONS THÉRAPEUTIQUES ASSOCIÉES
  申请人：QPEX BIOPHARMA INC

  公开号：WO2021226114A1

  公开（公告）日：2021-11-11

  Disclosed herein are antimicrobial compounds, polymorphic forms, compositions, pharmaceutical compositions, the method of use and preparation thereof. Some embodiments relate to boronic acid derivatives and their use as therapeutic agents, for example, β-lactamase inhibitors (BLIs).

  本文揭示了抗微生物化合物、多形态形式、组合物、药物组合物、使用方法和制备方法。一些实施例涉及硼酸衍生物及其用作治疗剂的用途，例如β-内酰胺酶抑制剂（BLIs）。