trans-3-(4-methoxyphenyl)-4-nitro-1-(phenylmethyl)pyrrolidine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: trans-3-(4-methoxyphenyl)-4-nitro-1-(phenylmethyl)pyrrolidine
• 英文别名: 1-benzyl-3-(4-methoxyphenyl)-4-nitropyrrolidine；(3S,4R)-1-benzyl-3-(4-methoxyphenyl)-4-nitropyrrolidine
• 化学式: C₁₈H₂₀N₂O₃
• 分子量: 312.368
• InChiKey: IFUHSIULUFPYKO-MSOLQXFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  58.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  trans-3-(4-methoxyphenyl)-4-nitro-1-(phenylmethyl)pyrrolidine 在 乙醇 、 tin(ll) chloride 作用下， 以 乙酸乙酯 为溶剂， 生成 (3S,4R)-1-benzyl-4-(4-methoxyphenyl)pyrrolidin-3-amine
  参考文献：
  名称：

  Synthesis of a Drug-Like Focused Library of Trisubstituted Pyrrolidines Using Integrated Flow Chemistry and Batch Methods

  摘要：

  A combination of flow and batch chemistries has been successfully applied to the assembly of a series of trisub-stituted drug-like pyrrolidines. This study demonstrates the efficient preparation of a focused library of these pharmaceutically important structures using microreactor technologies, as well as classical parallel synthesis techniques, and thus exemplifies the impact of integrating innovative enabling tools within the drug discovery process.

  DOI：

  10.1021/co2000357
• 作为产物：
  描述：

  4-甲氧基-β-硝基苯乙烯 、 N-(甲氧甲基)-N-(三甲基硅甲基)苄胺 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 以81%的产率得到trans-3-(4-methoxyphenyl)-4-nitro-1-(phenylmethyl)pyrrolidine
  参考文献：
  名称：

  Synthesis and antimicrobial evaluation of a series of 7-[3-amino (or aminomethyl)-4-aryl (or cyclopropyl)-1-pyrrolidinyl]-4-quinolone and -1,8-naphthyridone-3-carboxylic acids

  摘要：

  A series of 6-fluoroquinolone- and 6-fluoro-1,8-naphthyridone-3-carboxylic acids possessing a [3-amino (or aminomethyl)-4-aryl (or cyclopropyl)-1-pyrrolidinyl] group at C-7 were synthesized and evaluated for their antimicrobial activity. The effect of the relative stereochemistry of the pyrrolidinyl substituents, as well as the presence of different functional groups on the 4-aryl (or cyclopropyl) moiety, was investigated in conjunction with their attachment to several quinolone or naphthyridone nuclei. In general, the incorporation of substituents on the aryl (or cyclopropyl) ring decreased in vitro and in vivo activity, regardless of the nature and relative position of the substituent. Bulky, lipophilic groups and substitution at the 2- and 3-position of the aromatic ring were particularly deleterious. Within a limited subset of derivatives, cis substitution of the pyrrolidine ring was less favorable than trans substitution. The majority of these effects were more apparent against the Enterobacteriaceae than against any other Gram-negative or Gram-positive organism and could be associated with negative interactions related to permeability or transport factors.

  DOI：

  10.1021/jm00078a002

文献信息

• [EN] THERAPEUTIC OXY-PHENYL-ARYL COMPOUNDS AND THEIR USE<br/>[FR] COMPOSÉS OXY-PHÉNYL-ARYLES THÉRAPEUTIQUES ET LEUR UTILISATION
  申请人：CANCER REC TECH LTD

  公开号：WO2009053694A1

  公开（公告）日：2009-04-30

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain oxy phenyl aryl compounds (referred to herein as OPA compounds), as described herein, which, inter alia, inhibit Checkpoint Kinase 2 (CHK2) kinase function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CHK2 kinase function, and in the treatment of diseases and conditions that are mediated by CHK2, that are ameliorated by the inhibition of CHK2 kinase function, etc., including proliferative conditions such as cancer, etc., optionally in combination with another agent, for example, (a) a DNA topoisomerase I or II inhibitor; (b) a DNA damaging agent; (c) an antimetabolite or TS inhibitor; (d) a microtubule targeted agent; and (e) ionising radiation.

  本发明总体涉及治疗化合物领域，更具体地涉及如本文所述的某些氧基苯基芳基化合物（以下简称OPA化合物），其中，抑制检查点激酶2（CHK2）激酶功能。本发明还涉及包含此类化合物的药物组合物，以及使用此类化合物和组合物，在体内外抑制CHK2激酶功能，以及治疗由CHK2介导的疾病和状况，包括通过抑制CHK2激酶功能而改善的疾病和状况，等等，包括诸如癌症等增殖性疾病，可选地与另一剂联合使用，例如，（a）DNA拓扑异构酶I或II抑制剂；（b）DNA损伤剂；（c）抗代谢物或TS抑制剂；（d）针对微管的药剂；（e）电离辐射。
• Synthesis of 3-Nitropyrrolidines via Dipolar Cycloaddition Reactions Using a Modular Flow Reactor
  作者：Steven Ley、Marcus Baumann、Ian Baxendale

  DOI：10.1055/s-0029-1219344

  日期：2010.3

  The generation and subsequent use of unstabilised azomethine ylides in dipolar cycloaddition reactions within a flow microreactor is demonstrated. The 3-nitropyrrolidines produced were furthermore subjected to chemoselective hydrogenation reac- tions using the H-Cube ® system. To ensure product purities in ex- cess of 90-95%, immobilised scavengers were successfully employed.

  演示了在流动微反应器内的偶极环加成反应中不稳定的偶氮甲碱叶立德的产生和随后的使用。使用 H-Cube ® 系统进一步对生产的 3-硝基吡咯烷进行化学选择性氢化反应。为确保产品纯度超过 90-95%，成功使用了固定化清除剂。
• Synthesis of Highly Substituted Nitropyrrolidines, Nitropyrrolizines and Nitropyrroles via Multicomponent-Multistep Sequences within a Flow Reactor
  作者：Steven V. Ley、Marcus Baumann、Ian R. Baxendale、Andreas Kirschning、Jens Wegner

  DOI：10.3987/com-10-s(e)77

  日期：——

  3-nitropyrrolidines via a flow chemistry sequence. This new work describes the development of a three-component coupling reaction between glycine esters, aldehydes and nitro alkenes. In order to further demonstrate the utility of flow technology in concert with heterogeneous reagents and scavengers for complex reaction sequences an in-line oxidation resulting in the conversion of tetra-substituted pyrrolidines

  我们扩展了最近关于不稳定的偶氮甲碱叶立德与硝基烯烃的偶极环加成反应通过流动化学序列生成 3-硝基吡咯烷的结果。这项新工作描述了甘氨酸酯、醛和硝基烯烃之间的三组分偶联反应的发展。为了进一步证明流动技术与多相试剂和清除剂一起用于复杂反应序列的效用，已经开发了一种在线氧化，从而导致四取代的吡咯烷转化为其吡咯同系物。‡本文献给 Albert Eschenmoser 教授 85 岁生日，并感谢他对化学的许多杰出贡献。引言现代药物发现计划的一个必要要求是灵活快速地访问大量不同的功能化构建块。这些核心结构通常是杂环基序，它们是通过大量稳健的化学转化获得的。此外，杂环框架提供了与生物靶标的易于调节的相互作用，以帮助筛选的最佳结合数据。在这些杂环结构中，吡咯烷环具有特别的药用意义。它不仅存在于许多肽模拟物中，而且还存在于许多 HETEROCYCLES，Vol. 2011年82期2号1297 此外，杂环框架提
• [EN] PYRROLIDINE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM, AND THEIR USE IN THERAPY<br/>[FR] DÉRIVÉS DE PYRROLIDINE, COMPOSITIONS PHARMACEUTIQUES LES CONTENANT, ET LEUR UTILISATION EN THÉRAPIE
  申请人：ABBVIE DEUTSCHLAND

  公开号：WO2014140310A1

  公开（公告）日：2014-09-18

  The present invention relates to pyrrolidine derivatives of formula (I), or a physiologically tolerated salt thereof. The invention relates to pharmaceutical compositions comprising such pyrrolidine derivatives, and the use of such pyrrolidine derivatives for therapeutic purposes. The pyrrolidine derivatives are GlyT1 inhibitors.

  本发明涉及式(I)的吡咯烷衍生物，或其生理耐受盐。该发明涉及包含此类吡咯烷衍生物的药物组合物，以及利用此类吡咯烷衍生物进行治疗的用途。这些吡咯烷衍生物是GlyT1抑制剂。
• Therapeutic Oxy-Phenyl-Aryl Compounds and Their Use
  申请人：Collins Ian

  公开号：US20110201592A1

  公开（公告）日：2011-08-18

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain oxy phenyl aryl compounds (referred to herein as OPA compounds), as described herein, which, inter alia, inhibit Checkpoint Kinase 2 (CHK2) kinase function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CHK2 kinase function, and in the treatment of diseases and conditions that are mediated by CHK2, that are ameliorated by the inhibition of CHK2 kinase function, etc., including proliferative conditions such as cancer, etc., optionally in combination with another agent, for example, (a) a DNA topoisomerase I or II inhibitor; (b) a DNA damaging agent; (c) an antimetabolite or TS inhibitor; (d) a microtubule targeted agent; and (e) ionising radiation.

  本发明涉及治疗化合物领域，更具体地涉及某些氧苯基芳基化合物（以下简称OPA化合物），如本文所述，该化合物在其中抑制检查点激酶2（CHK2）激酶功能。本发明还涉及包含这种化合物的制药组合物，以及在体外和体内使用这种化合物和组合物来抑制CHK2激酶功能，并治疗由CHK2介导，通过抑制CHK2激酶功能改善的疾病和病况，包括增殖性疾病，如癌症等，可选择与另一种药物一起使用，例如（a）DNA拓扑异构酶I或II抑制剂；（b）DNA损伤剂；（c）抗代谢物或TS抑制剂；（d）微管靶向药物；和（e）电离辐射。