ethyl (1-(methoxy(methyl)amino)-1-oxopropan-2-yl)carbamate | 89312-80-1

• 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: ethyl (1-(methoxy(methyl)amino)-1-oxopropan-2-yl)carbamate
• 英文别名: N-(ethoxycarbonyl)-L-alanine N-methoxy-N-methylamide；N-ethoxycarbonyl-N'-methoxy-N'-methyl-L-alaninamide；ethyl N-[(2S)-1-[methoxy(methyl)amino]-1-oxopropan-2-yl]carbamate
• CAS: 89312-80-1
• 化学式: C₈H₁₆N₂O₄
• 分子量: 204.226
• InChiKey: FLXAZMBAOWQXMH-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl (1-(methoxy(methyl)amino)-1-oxopropan-2-yl)carbamate 在 zinc tetrafluoroborate 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 4.0h， 生成 ethyl ((anti)-1-hydroxy-1-(p-tolyl)propan-2-yl)carbamate
  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：

  N-乙氧基羰基-L-丙氨酸 在 吡啶 、 草酰氯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 ethyl (1-(methoxy(methyl)amino)-1-oxopropan-2-yl)carbamate
  参考文献：
  名称：

  .alpha.-Amino acids as chiral educts for asymmetric products. The synthesis of .alpha.'-amino-.alpha.,.beta.-ynones

  摘要：

  DOI：

  10.1021/jo00221a004

文献信息

• Synthesis of [14C]CI-980, ethyl [5-amino-1,2-dihydro-2(S)-methyl-3-[14C]phenylpyrido[3,4- 6]pyrazin-7-YL]carbamate isethionate salt, a tubulin-binding, antimitotic, broad-spectrum antitumor agent
  作者：Peter W. K. Woo、Helen T. Lee

  DOI：10.1002/jlcr.2580340102

  日期：1994.1

  [14C]CI-980 (14b) was synthesized in eight steps starting from [U-14C]benzene (5), which was converted to bromo[14C]benzene (6) in the presence of tetrabutylammonium bromide as catalyst. Reaction of 6 with the anion of N-ethoxycarbonyl-N′-methoxy-N′-methyl-L-alaninamide (4a) gave the chiral (S)-ketone 8 with ee exceeding 96%. Sodium borohydride reduction of 8, followed by sequential condensation with ethyl 6-amino-4-chloro-5-nitro-2-pyridine carbamate (11), chromium trioxide oxidation, and catalytic hydrogenation over Raney nickel gave the free base form of [14C]CI-980 (14a), which was extremely unstable and readily aromatized to 15. The free base 14a was, however, isolated under specially developed conditions and converted to the crystalline isethionate salt 14b in pure form.

  [14C]CI-980（14b）是以[U-14C]苯（5）为起点，在四丁基溴化铵作为催化剂的存在下，分八个步骤合成的，然后将[U-14C]苯（5）转化为溴[14C]苯（6）。6 与 N-乙氧羰基-N′-甲氧基-N′-甲基-L-丙氨酰胺（4a）的阴离子反应，得到手性（S）-酮 8，ee 超过 96%。硼氢化钠还原 8，然后依次与 6-氨基-4-氯-5-硝基-2-吡啶氨基甲酸乙酯（11）缩合、三氧化铬氧化和在雷尼镍上催化加氢，得到游离碱形式的 [14C]CI-980 (14a)，它极不稳定，很容易芳香化为 15。不过，游离碱 14a 在专门开发的条件下被分离出来，并以纯净的形式转化为晶体状的异硫酸盐 14b。
• Compounds, Compositions, and Methods for Treating T-Cell Acute Lymphoblastic Leukemia
  申请人：The Trustees of Columbia University in the City of New York

  公开号：US20200165211A1

  公开（公告）日：2020-05-28

  In an aspect, the disclosure provides for compounds (II), compositions, and methods of administering the compounds and compositions to a patient in need thereof. In another aspect, the disclosure relates to compounds and compositions for treating cancer, for example, lymphoid leukemia. The disclosure further provides for compounds which inhibit two phosphoinositide 3-kinase (PI3K) isoforms, y and δ, pharmaceutical compositions comprising said compounds, and methods of using said compounds and pharmaceutical compositions for treatment, amelioration, and/or prevention of non-Hodgkin lymphoma.
• .alpha.-Amino acids as chiral educts for asymmetric products. The synthesis of .alpha.'-amino-.alpha.,.beta.-ynones
  作者：Thomas L. Cupps、Raymond H. Boutin、Henry Rapoport

  DOI：10.1021/jo00221a004

  日期：1985.10
• Phase I metabolites of mephedrone display biological activity as substrates at monoamine transporters
  作者：F P Mayer、L Wimmer、O Dillon‐Carter、J S Partilla、N V Burchardt、M D Mihovilovic、M H Baumann、H H Sitte

  DOI：10.1111/bph.13547

  日期：2016.9

  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.