2-甲基氨基-1-(3,4-亚甲二氧苯基)-1-丙酮盐酸盐 | 186028-80-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 中文名称: 2-甲基氨基-1-(3,4-亚甲二氧苯基)-1-丙酮盐酸盐
• 中文别名: 1-(1,3-苯并二氧-5-基)-2-(甲基氨基)-1-丙酮盐酸盐
• 英文名称: Methylone hydrochloride
• 英文别名: 1-(1,3-benzodioxol-5-yl)-2-(methylamino)propan-1-one;hydrochloride
• CAS: 186028-80-8
• 化学式: C₁₁H₁₃NO₃*ClH
• 分子量: 243.69
• InChiKey: GASYWEXOTOXXLK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.63
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  47.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-甲基氨基-1-(3,4-亚甲二氧苯基)-1-丙酮盐酸盐 在 三溴化硼 、 甲醇 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以19%的产率得到3,4-dihydroxymethcathinone
  参考文献：
  名称：

  In Vitro Metabolism and Pharmacokinetic Studies on Methylone

  摘要：

  世界大部分地区都有滥用兴奋剂特制药物甲酮（亚甲二氧基甲卡西酮）的记录。与非法药物市场上不断出现的许多新型特制药物一样，人们对甲酮的药代动力学知之甚少。通过体外研究，确定 CYP2D6 是代谢甲酮的主要酶，CYP1A2、CYP2B6 和 CYP2C19 对其代谢作用较小。主要代谢物被确定为二羟基甲卡西酮，次要代谢物为 N -羟基甲酮、去甲甲酮和二氢甲酮。通过测定主要代谢物的形成过程，确定了双相迈克尔-门顿动力学参数：V max,1 = 0.046 ± 0.005 (S.E.) nmol/min/mg 蛋白质，K m,1 = 19.0 ± 4.2 μ M，V max,2 = 0.22 ± 0.04 nmol/min/mg 蛋白质，K m,2 = 1953 ± 761 μ M；低能力和高亲和力的贡献归因于 CYP2D6 的活性。此外，当 CYP2D6 与甲缩醛预孵育时，观察到 CYP2D6 活性的丧失与时间有关，在高浓度甲缩醛时达到最大失活率，这表明甲缩醛是一种基于机制的 CYP2D6 抑制剂。灭活参数被确定为 K I = 15.1 ± 3.4 (S.E.) μ M 和 k inact = 0.075 ± 0.005 minute-1。

  DOI：

  10.1124/dmd.112.050880
• 作为产物：
  描述：

  亚甲基二氧基甲卡西酮 在 盐酸 作用下， 以 乙醚 为溶剂， 以94 %的产率得到2-甲基氨基-1-(3,4-亚甲二氧苯基)-1-丙酮盐酸盐
  参考文献：
  名称：

  [EN] ISOTOPOLOGES, SALTS, CRYSTALLINE FORMS, STEREOISOMERS, OF METHYLONE AND ETHYLONE AND METHODS OF USE THEREOF
  [FR] ISOTOPOLOGUES, SELS, FORMES CRISTALLINES, STÉRÉOISOMÈRES, DE MÉTHYLONE ET D'ÉTHYLONE ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  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.

  公开号：

  WO2023081403A1

文献信息

• X-ray structures and computational studies of several cathinones
  作者：Jacek E. Nycz、Grzegorz Malecki、Marcin Zawiazalec、Tadeusz Pazdziorek

  DOI：10.1016/j.molstruc.2011.06.030

  日期：2011.9

  2-(Ethylamino)-1-(4-methylphenyl)propan-l-one (shortly named 4-MEC) (1a), 1-(1,3-benzodioxol-5-yl)-2-(methylamino)propan-1-one (shortly named methylone or 3,4-methylenedioxymethcathinone) (1b), 1-(3,4-dimethylphenyl)-2-(methylamino)propan-1-one (1c), 2-methylamino-1-(4-methylphenyl)propan-1 -one (shortly named mephedrone; 4-MMC or 4-methylmethcathinone) (1d) and 2-(methylamino)-1-phenylbutan-1 -one (shortly named buphedrone) (1e) and their aminium salts (2a-e), are examples of cathinones which were characterized by FTIR, UV-Vis, multinuclear NMR spectroscopy. By single crystal X-ray diffraction method structures of 2a, 2h, 2c and 2d were determined. NMR solution spectra showed readily diagnostic H-1 and C-13 signals from methyl, ethyl, N-methyl or N-ethyl groups. The diastereotopic methylene protons of la appear as an ABX(3), and le and 2e appear as an ABMX(3) system. The geometries of the studied compounds were optimized in singlet states using the density functional theory (OFT) method with B3LYP functional. Electronic spectra were calculated by TDDFT method. In general, the predicted bond lengths and angles are in good agreement with the values based on the X-ray crystal structure data. (C) 2011 Elsevier B.V. All rights reserved.
• PHENETHYLAMINES AND CATHINONES PRECURSORS
  申请人：[en]TRANSCEND THERAPEUTICS, INC.

  公开号：WO2024039599A1

  公开（公告）日：2024-02-22

  The subject matter disclosed generally relates to phenethylamines or cathinones covalently bound to a chemical moiety in a prodrug form. The presently described technology allows slow/sustained/controlled delivery of the parent phenethylamines or cathinones into the blood system in a manner that increase the duration of therapeutic efficacy, ease of application, patient compliance and/or a combination of these characteristics when administered, in particular, orally. Additionally, the described technology allows gradual release of the parent phenethylamines or cathinones over an extended period of time thereby eliminating spiking of drug levels which lessen cardiovascular stress, addiction/abuse potential and/or other common stimulant side effects associated with psychoactive compounds.
• WO2023/137453
  申请人：——

  公开号：——

  公开（公告）日：——
• In Vitro Metabolism and Pharmacokinetic Studies on Methylone
  作者：Anders Just Pedersen、Trine Hedebrink Petersen、Kristian Linnet

  DOI：10.1124/dmd.112.050880

  日期：2013.6

  Abuse of the stimulant designer drug methylone (methylenedioxymethcathinone) has been documented in most parts of the world. As with many of the new designer drugs that continuously appear in the illicit drug market, little is known about the pharmacokinetics of methylone. Using in vitro studies, CYP2D6 was determined to be the primary enzyme that metabolizes methylone, with minor contributions from CYP1A2, CYP2B6, and CYP2C19. The major metabolite was identified as dihydroxymethcathinone, and the minor metabolites were N -hydroxy-methylone, nor-methylone, and dihydro-methylone. Measuring the formation of the major metabolite, biphasic Michaelis–Menten kinetic parameters were determined: V max,1 = 0.046 ± 0.005 (S.E.) nmol/min/mg protein, K m,1 = 19.0 ± 4.2 μ M, V max,2 = 0.22 ± 0.04 nmol/min/mg protein, and K m,2 = 1953 ± 761 μ M; the low-capacity and high-affinity contribution was assigned to the activity of CYP2D6. Additionally, a time-dependent loss of CYP2D6 activity was observed when the enzyme was preincubated with methylone, reaching a maximum rate of inactivation at high methylone concentrations, indicating that methylone is a mechanism-based inhibitor of CYP2D6. The inactivation parameters were determined to be K I = 15.1 ± 3.4 (S.E.) μ M and k inact = 0.075 ± 0.005 minute−1.

  世界大部分地区都有滥用兴奋剂特制药物甲酮（亚甲二氧基甲卡西酮）的记录。与非法药物市场上不断出现的许多新型特制药物一样，人们对甲酮的药代动力学知之甚少。通过体外研究，确定 CYP2D6 是代谢甲酮的主要酶，CYP1A2、CYP2B6 和 CYP2C19 对其代谢作用较小。主要代谢物被确定为二羟基甲卡西酮，次要代谢物为 N -羟基甲酮、去甲甲酮和二氢甲酮。通过测定主要代谢物的形成过程，确定了双相迈克尔-门顿动力学参数：V max,1 = 0.046 ± 0.005 (S.E.) nmol/min/mg 蛋白质，K m,1 = 19.0 ± 4.2 μ M，V max,2 = 0.22 ± 0.04 nmol/min/mg 蛋白质，K m,2 = 1953 ± 761 μ M；低能力和高亲和力的贡献归因于 CYP2D6 的活性。此外，当 CYP2D6 与甲缩醛预孵育时，观察到 CYP2D6 活性的丧失与时间有关，在高浓度甲缩醛时达到最大失活率，这表明甲缩醛是一种基于机制的 CYP2D6 抑制剂。灭活参数被确定为 K I = 15.1 ± 3.4 (S.E.) μ M 和 k inact = 0.075 ± 0.005 minute-1。
• [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.