tert-butyl (S)-1-(N-methoxy-N-methylcarbamoyl)ethylmethylcarbamate | 170097-58-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl (S)-1-(N-methoxy-N-methylcarbamoyl)ethylmethylcarbamate
• 英文别名: tert-butyl (1-(methoxy(methyl)amino)-1-oxopropan-2-yl)(methyl)carbamate；(S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxopropan-2-yl)(methyl)carbamate；tert-butyl N-[(2S)-1-[methoxy(methyl)amino]-1-oxopropan-2-yl]-N-methylcarbamate
• CAS: 170097-58-2
• 化学式: C₁₁H₂₂N₂O₄
• 分子量: 246.307
• InChiKey: MXNQKIPLJZAZBI-QMMMGPOBSA-N

物化性质

• 沸点：
  291.6±33.0 °C(Predicted)
• 密度：
  1.061±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  59.1
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  tert-butyl (S)-1-(N-methoxy-N-methylcarbamoyl)ethylmethylcarbamate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 tert-butyl (S)-methyl(1-oxopropan-2- yl)carbamate
  参考文献：
  名称：

  Synthesis and Antimitotic/Cytotoxic Activity of Hemiasterlin Analogues

  摘要：

  The antimitotic sponge tripeptide hemiasterlin (1) and a number of structural analogues have been synthesized and evaluated in cell-based assays for both cytotoxic and antimitotic activity in order to explore the SAR for this promising anticancer drug lead. One synthetic analogue, SPA110 (8), showed more potent in vitro cytotoxicty and antimitotic activity than the natural product hemiasterlin (1), and consequently it has been subjected to thorough preclinical evaluation and targeted for clinical evaluation. The details of the synthesis of hemiasterlin (1) and the analogues and a discussion of how their biological activities vary with their structures are presented in this paper.

  DOI：

  10.1021/np020375t
• 作为产物：
  描述：

  N-叔丁氧羰基-L-丙氨酸 在 sodium hydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 25.0h， 生成 tert-butyl (S)-1-(N-methoxy-N-methylcarbamoyl)ethylmethylcarbamate
  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

• Stereochemistry of mephedrone neuropharmacology: enantiomer-specific behavioural and neurochemical effects in rats
  作者：Ryan A Gregg、Michael H Baumann、John S Partilla、Julie S Bonano、Alexandre Vouga、Christopher S Tallarida、Venkata Velvadapu、Garry R Smith、M Melissa Peet、Allen B Reitz、S Stevens Negus、Scott M Rawls

  DOI：10.1111/bph.12951

  日期：2015.2

  Background and PurposeSynthetic cathinones, commonly referred to as ‘bath salts’, are a group of amphetamine‐like drugs gaining popularity worldwide. 4‐Methylmethcathinone (mephedrone, MEPH) is the most commonly abused synthetic cathinone in the UK, and exerts its effects by acting as a substrate‐type releaser at monoamine transporters. Similar to other cathinone‐related compounds, MEPH has a chiral centre and exists stably as two enantiomers: R‐mephedrone (R‐MEPH) and S‐mephedrone (S‐MEPH).Experimental ApproachHere, we provide the first investigation into the neurochemical and behavioural effects of R‐MEPH and S‐MEPH. We analysed both enantiomers in rat brain synaptosome neurotransmitter release assays and also investigated their effects on locomotor activity (e.g. ambulatory activity and repetitive movements), behavioural sensitization and reward.Key ResultsBoth enantiomers displayed similar potency as substrates (i.e. releasers) at dopamine transporters, but R‐MEPH was much less potent than S‐MEPH as a substrate at 5‐HT transporters. Locomotor activity was evaluated in acute and repeated administration paradigms, with R‐MEPH producing greater repetitive movements than S‐MEPH across multiple doses. After repeated drug exposure, only R‐MEPH produced sensitization of repetitive movements. R‐MEPH produced a conditioned place preference whereas S‐MEPH did not. Lastly, R‐MEPH and S‐MEPH produced biphasic profiles in an assay of intracranial self‐stimulation (ICSS), but R‐MEPH produced greater ICSS facilitation than S‐MEPH.Conclusions and ImplicationsOur data are the first to demonstrate stereospecific effects of MEPH enantiomers and suggest that the predominant dopaminergic actions of R‐MEPH (i.e. the lack of serotonergic actions) render this stereoisomer more stimulant‐like when compared with S‐MEPH. This hypothesis warrants further study.
• US5726185A
  申请人：——

  公开号：US5726185A

  公开（公告）日：1998-03-10
• [EN] ISOTOPOLOGES, SALTS, CRYSTALLINE FORMS, STEREOISOMERS, OF METHYLONE AND ETHYLONE AND METHODS OF USE THEREOF<br/>[FR] ISOTOPOLOGUES, SELS, FORMES CRISTALLINES, STÉRÉOISOMÈRES, DE MÉTHYLONE ET D'ÉTHYLONE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：[en]TERRAN BIOSCIENCES INC.

  公开号：WO2023081403A1

  公开（公告）日：2023-05-11

  Described herein are isotopically enriched analogs of methylone (e.g., deuterated analogs of methylone (e.g., (S)-methylone and (R)-methylone) with improved characteristics. Also described herein are salts (such as hydrochloride salt) and solid forms (e.g., crystalline forms) of methylone. Also described herein are stereoisomers (e.g., enantiomers) of methylone. The present disclosure also provides methods of making and methods of use of the methylone or methylone analogs and solid forms of 3,4-methylenedioxy-N-ethylcathinone hydrochloride described herein to treat brain and neurological disorders such as depression.