ethyl (+/-)-cis-2-(bromomethyl)-1-phenylcyclopropanecarboxylate | 105310-49-4

• 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: ethyl (+/-)-cis-2-(bromomethyl)-1-phenylcyclopropanecarboxylate
• 英文别名: (Z)-ethyl 1-phenyl-2-(bromomethyl)cyclopropanecarboxylate；ethyl (1R,2S)-2-(bromomethyl)-1-phenylcyclopropane-1-carboxylate
• CAS: 105310-49-4
• 化学式: C₁₃H₁₅BrO₂
• 分子量: 283.165
• InChiKey: ACZOETNIVCDANN-YPMHNXCESA-N

物化性质

• 沸点：
  105-110 °C(Press: 0.1 Torr)
• 密度：
  1.386±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  甲基丁胺 、 ethyl (+/-)-cis-2-(bromomethyl)-1-phenylcyclopropanecarboxylate 在 potassium iodide 作用下， 生成 ethyl (1R,2S)-2-[[butyl(methyl)amino]methyl]-1-phenylcyclopropane-1-carboxylate
  参考文献：
  名称：

  1-芳基-2-（氨基甲基）环丙烷羧酸衍生物。一系列潜在的抗抑郁药。

  摘要：

  合成了一系列的1-芳基-2-（氨基甲基）环丙烷羧酸衍生物，并将其评估为潜在的抗抑郁药。具有Z构型的化合物由1-芳基-2-氧代-3-氧杂双环[3.1.0]己烷合成，具有E构型的化合物由（E）-1-苯基-2-（羟甲基）环丙烷羧酸合成。在动物试验中对化合物进行了评估，旨在揭示其潜在的抗抑郁活性和不良副作用的存在。几种衍生物比丙咪嗪和地昔帕明更具活性。根据其在抗抑郁药理动物实验中的活性及其潜在的无副作用，选择了1-苯基-1-[（（二乙基氨基）羰基] -2-（氨基甲基）环丙烷盐酸盐，中alcipranan（INN）。进一步的发展。

  DOI：

  10.1021/jm00385a013
• 作为产物：
  描述：

  (1R,2S)-2-(bromomethyl)-1-phenylcyclopropanecarboxylic acid 在 盐酸 、 氯化亚砜 作用下， 以 苯 为溶剂， 反应 5.0h， 生成 ethyl (+/-)-cis-2-(bromomethyl)-1-phenylcyclopropanecarboxylate
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of potent and enantioselective σ1 and σ2 ligands

  摘要：

  In a previous study we found that substitutions of the (+)-cis-N-normetazocine nucleus of (+)-MPCB with 1-adamantanamine provide the compound (+/-)-10 with high affinity and selectivity for sigma receptors. Starting with this result we have synthesized a new series of eight 1-phenyl-2-cyclopropylmethylamines structurally related to (+/-)-10, and binding affinities, with respect to sigma(1), sigma(2), opioid and dopaminergic D-2 receptors, have been reported. All compounds showed a negligible opioid and dopaminergic affinity and high selectivity for sigma receptors. Modifications on the amino moiety and methylcarboxyester group of 10 provide compounds with different sigma(1), and sigma(2) binding affinity and selectivity. Moreover, we have also synthesized the respective enantiomers of componds (+/-)-10 and (+/-)-18 in order to evaluate the enantioselectivity for sigma(1) and sigma(2) receptors. The binding data showed that carboxymethylester on the cyclopropane ring was more critical for enantioselectivity than the hydroxymethylenic group. In fact, the (-)-10 enantionter showed a preference for sigma(1) whereas (+)-10 showed a preference for sigma(2), (C) 2001 Elsevier Science S.A. All rights reserved.

  DOI：

  10.1016/s0014-827x(01)01039-4

文献信息

• (+)-Methyl (1<i>R</i>,2<i>S</i>)-2-{[4-(4-Chlorophenyl)-4-hydroxypiperidin-1-yl]methyl}-1-phenylcyclopropanecarboxylate [(+)-MR200] Derivatives as Potent and Selective Sigma Receptor Ligands: Stereochemistry and Pharmacological Properties
  作者：Emanuele Amata、Antonio Rescifina、Orazio Prezzavento、Emanuela Arena、Maria Dichiara、Valeria Pittalà、Ángeles Montilla-García、Francesco Punzo、Pedro Merino、Enrique J. Cobos、Agostino Marrazzo

  DOI：10.1021/acs.jmedchem.7b01584

  日期：2018.1.11

  Methoxycarbonyl-1-phenyl-2-cyclopropylmethyl based derivatives cis-(+)-1a [cis-(+)-MR200], cis-(−)-1a [cis-(−)-MR201], and trans-(±)-1a [trans-(±)-MR204], have been identified as new potent sigma (σ) receptor ligands. In the present paper, novel enantiomerically pure analogues were synthesized and optimized for their σ receptor affinity and selectivity. Docking studies rationalized the results obtained

  基于甲氧羰基-1-苯基-2-环丙基甲基的衍生物cis -（+）- 1a [ cis -（+）-MR200]，cis -（-）- 1a [ cis -（-）-MR201]和反式-（± ） - 1A [反式- （±）-MR204]，已被确定为新的有效西格玛（σ）受体配体。在本文中，合成了新颖的对映体纯类似物，并针对其σ受体亲和力和选择性进行了优化。对接研究使在放射性配体结合测定中获得的结果合理化。通过对前体反式-（+）- 5a作为樟脑磺酰基衍生物的X射线分析明确建立了绝对立体化学9。最有前途的化合物反式（（+）- 1d）在超过15种受体上显示出显着的选择性，并在人血浆中具有良好的化学和酶稳定性。体内评价证明该反式- （+） - 1D，而相比之下，反式- （ - ） - 1D，顺式- （+） - 1D，或顺式- （ - ） - 1D，其表现为σ 1拮抗剂，表现出一个σ 1激动剂曲线。这些数据清楚地表明，化合物反式-
• Substituted 1-phenyl-2-cyclopropylmethylamines with high affinity and selectivity for sigma sites
  作者：Giuseppe Ronsisvalle、Agostino Marrazzo、Orazio Prezzavento、Lorella Pasquinucci、Barbara Falcucci、Rosanna Di Toro、Santi Spampinato

  DOI：10.1016/s0968-0896(00)00072-9

  日期：2000.6

  A series of 1-phenyl-2-cyclopropylmethylamines structurally related to (+)- and (-)-MPCB were synthesized and their binding affinities for or, oz, opioid and dopamine (D-2) receptors were evaluated. Substitution of the cis-N-normetazocine with different aminic moieties provided compounds with high affinity and selectivity for sigma binding sites with respect to opioid and dopamine (D2) receptors. The observed increase in sigma(2) affinity as compared to the parent(+)-MPCB, supports the idea that the particular stereochemistry of (+)-cis-N-normetazocine affects sigma(1) selectivity but does not affect ol affinity. The (+/-)-cis isomers of methyl 2-[(1-adamantylamino)methyl]-1-phenylcyclopropane-1-carboxylate (18) displayed a higher affinity and selectivity for the ol and sigma(2) receptor subtypes compared to the (+/-)-trans 19. interestingly, the enantiomer (-)-cis 18 displayed a preference for ol receptor subtype whereas the (+)-cis 18 did for sigma(2). These results prompt us to synthesize compounds with modification of nitrogen and carboxyl groups. The compounds obtained showed high affinities and selectivity for sigma sites. Moreover, modifications of carboxyl groups provided compounds with the highest affinities in the series. In particular, compound 25 with reverse-type ester showed a K-i of 0.6 and 4.05 nM for sigma(1) and sigma(2) binding sites, respectively. (C) 2000 Elsevier Science Ltd. All rights reserved.
• BONNAUD B.; COUSSE H.; MOUZIN G.; BRILEY M.; STENGER A.; FAURAN F.; COUZI+, J. MED. CHEM., 30,(1987) N 2, 318-325
  作者：BONNAUD B.、 COUSSE H.、 MOUZIN G.、 BRILEY M.、 STENGER A.、 FAURAN F.、 COUZI+

  DOI：——

  日期：——