(+/-)-methyl cis-2-(bromomethyl)-1-phenylcyclopropanecarboxylate | 105310-48-3

• 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: (+/-)-methyl cis-2-(bromomethyl)-1-phenylcyclopropanecarboxylate
• 英文别名: rel-Methyl (1R,2S)-2-(bromomethyl)-1-phenylcyclopropanecarboxylate；methyl (1R,2S)-2-(bromomethyl)-1-phenylcyclopropane-1-carboxylate
• CAS: 105310-48-3
• 化学式: C₁₂H₁₃BrO₂
• 分子量: 269.138
• InChiKey: IYFSSGZAXORCOG-PWSUYJOCSA-N

物化性质

• 沸点：
  322.6±25.0 °C(Predicted)
• 密度：
  1.433±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.51
• 重原子数：
  15.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  26.3
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (+/-)-methyl cis-2-(bromomethyl)-1-phenylcyclopropanecarboxylate 在 sodium hydroxide 、 potassium iodide 作用下， 以 甲苯 、 苯 为溶剂， 生成 环丙羧酸,2-[(二甲氨基)甲基]-1-苯基-,顺-
  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 10.0h， 生成 (+/-)-methyl cis-2-(bromomethyl)-1-phenylcyclopropanecarboxylate
  参考文献：
  名称：

  Synthesis of (+)- and (−)-cis-2-[(1-adamantylamino)-methyl]-1-phenylcyclopropane derivatives as high affinity probes for σ1 and σ2 binding sites

  摘要：

  Selective ligands for either sigma(1) (sigma(1)) or sigma(2) binding sites are potentially useful for gaining a better understanding of the physiological functions of these proteins. Moreover, potent and selective homochiral sigma(1) and sigma(2) binding site ligands represent leads to potential radioligands for tumour imaging with positron emission tomography (PET). On the basis of their structural similarity to previous leads, new (+)- and (-)-cis-2-[(1-adamantylamino)-methyl]-1-phenylcyclopropane derivatives were synthesised and their binding affinities for sigma(1) and sigma(2) binding sites were determined. Each enantiomer showed high affinity for both sigma(1) and sigma(2) binding sites, but only (-)-cis-methyl-2-{[1-adamantyl(methyl)amino]methyl}-1-phenylcyclopropane-carboxylate, (-)-4, showed appreciable selectivity for binding to sigma(1) versus sigma(2) sites. The enantiomers of cis-(2-{[1-adamantyl(methyl)amino]methyl}-1-phenylcyclopropyl)methanol, 6, expressed the highest affinity for sigma(1) and sigma(2) binding sites. Ligands (-)-4, (+)-6 and (-)-6 might be rapidly labelled in their N-methyl groups by methylation of the N-desmethyl analogues with [C-11]iodomethane to provide prospective radioligands for PET. The N-desmethyl analogues, which are also high affinity ligands, were prepared and shown to undergo satisfactory methylation with iodomethane. (C) 2002 Elsevier Science S.A. All rights reserved.

  DOI：

  10.1016/s0014-827x(01)01170-3

文献信息

• Synthesis and pharmacological evaluation of potent and enantioselective σ1 and σ2 ligands
  作者：Agostino Marrazzo、Orazio Prezzavento、Lorella Pasquinucci、Franco Vittorio、Giuseppe Ronsisvalle

  DOI：10.1016/s0014-827x(01)01039-4

  日期：2001.4

  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.
• 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.
• Novel Potent and Selective σ Ligands: Evaluation of Their Agonist and Antagonist Properties
  作者：Agostino Marrazzo、Enrique J. Cobos、Carmela Parenti、Giuseppina Aricò、Giuseppina Marrazzo、Simone Ronsisvalle、Lorella Pasquinucci、Orazio Prezzavento、Nicola A. Colabufo、Marialessandra Contino、Luis G. González、Giovanna M. Scoto、Giuseppe Ronsisvalle

  DOI：10.1021/jm200144j

  日期：2011.5.26

  Novel enantiomers and diastereoisomers structurally related to sigma ligand (+)-MR200 were synthesized to improve sigma(1)/sigma(2) subtype selectivity. The selective sigma(1) ligand (-)-8 showed an antagonist profile determined by phenytoin differential modulation of binding affinity in vitro, confirmed in vivo by an increase of kappa opioid analgesia. The sigma(2) ligand (-)-9 displayed agonist properties in an in vitro isolated organ bath assay and antiproliferative effects on LNCaP and PC3 prostate cancer cell lines.
• A De Novo Designed Inhibitor ofD-Ala-D-Ala Ligase fromE. coli
  作者：Gilbert E. Besong、Julieanne M. Bostock、Will Stubbings、Ian Chopra、David I. Roper、Adrian J. Lloyd、Colin W. G. Fishwick、A. Peter Johnson

  DOI：10.1002/anie.200501662

  日期：2005.10.7
• 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：——