(rac.)-(1R*,5S*)-8-methyl-3-trifluoromethanesulfonyloxy-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylic acid 2-methyl ester

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磺酸及其衍生物
• 英文名称: (rac.)-(1R*,5S*)-8-methyl-3-trifluoromethanesulfonyloxy-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylic acid 2-methyl ester
• 英文别名: (rac.)-(1R*,5S*)-8-methyl-3-trifluoromethanesulfonyloxy-8-aza-bicyclo[3.2.1]oct-2-ene-2-carboxylic acid methyl ester；(rac.)-(1R*,5S*)-8-methyl-3-trifluoromethanesulfonyloxy-8-azabicyclo-[3.2.1]oct-2-ene-2-carboxylic acid methyl ester；(rac)-(1RS,5SR)-8-methyl-3-trifluoromethanesulfonyloxy-8-azabicyclo-[3.2.1]oct-2-ene-2-carboxylic acid methyl ester；(rac)-(1R,5S)-8-methyl-3-trifluoromethanesulfonyloxy-8-azabicyclo-[3.2.1]oct-2-ene-2-carboxylic acid methyl ester；methyl (1S,5R)-8-methyl-3-(trifluoromethylsulfonyloxy)-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate
• 化学式: C₁₁H₁₄F₃NO₅S
• 分子量: 329.297
• InChiKey: BFMAWIWAQIOLMT-RQJHMYQMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  81.3
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (rac.)-(1R*,5S*)-8-methyl-3-trifluoromethanesulfonyloxy-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylic acid 2-methyl ester 在 甲醇 、 正丁基锂 、 1-氯乙基氯甲酸酯 、 碳酸氢钠 、 magnesium 作用下， 以 四氢呋喃 、 正己烷 、 1,2-二氯乙烷 为溶剂， 反应 27.98h， 生成 (rac.)-(1R*,2R*,3S*,5S*)-3-(4-(2-(2,6-dichloro-4-methylphenoxy)ethoxy)phenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2,8-dicarboxylic acid 8-tert-butyl ester 2-methyl ester
  参考文献：
  名称：

  WO2007/88514

  摘要：

  公开号：
• 作为产物：
  描述：

  tropinone 在 sodium hydride 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 生成 (rac.)-(1R*,5S*)-8-methyl-3-trifluoromethanesulfonyloxy-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylic acid 2-methyl ester
  参考文献：
  名称：

  New classes of potent and bioavailable human renin inhibitors

  摘要：

  New classes of de novo designed renin inhibitors are reported. Some of these compounds display excellent in vitro and in vivo activities toward human renin in a TGR model. The synthesis of these new types of mono- and bicyclic scaffolds are reported, and properties of selected compounds discussed. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.09.104

文献信息

• Secondary Amines as Renin Inhibitors
  申请人：Bezencon Olivier

  公开号：US20090176823A1

  公开（公告）日：2009-07-09

  The invention relates to novel secondary amine derivatives of formula (I) and the use thereof as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as inhibitors of renin.

  这项发明涉及公式（I）的新型二级胺衍生物及其作为药物组成物中的活性成分的用途。该发明还涉及相关方面，包括制备这些化合物的过程、含有其中一个或多个这些化合物的药物组成物，特别是它们作为肾素抑制剂的用途。
• 3-Aryl-2-carbomethoxybicyclo[3.2.1]oct-2-enes inhibit WIN 35,428 binding potently and selectively at the dopamine transporter
  作者：Peter C. Meltzer、Paul Blundell、Hong Huang、Shanghao Liu、Yaw F. Yong、Bertha K. Madras

  DOI：10.1016/s0968-0896(99)00322-3

  日期：2000.3

  design of potential cocaine antagonists or cocaine substitutes which interact at the dopamine transporter of mammalian systems. This manuscript describes the synthesis and biological evaluation of 8-substituted 2-carbomethoxy-3-arylbicyclo[3.2.1]oct-2-enes. These compounds prove potent and selective inhibitors of the dopamine transporter. Their selectivity results primarily from a reduced inhibitory potency

  寻找可卡因滥用的药物的重点在于设计在哺乳动物系统多巴胺转运蛋白上相互作用的潜在可卡因拮抗剂或可卡因替代品。该手稿描述了8-取代的2-碳甲氧基-3-芳基双环[3.2.1]辛-2-烯的合成及生物学评估。这些化合物证明是多巴胺转运蛋白的有效和选择性抑制剂。它们的选择性主要是由于降低了对5-羟色胺转运蛋白的抑制能力。这项工作支持这样的观点，即在双环[3.2.1]辛烷体系中3-芳基环的取向对这些分子与5-羟色胺转运蛋白的相互作用的影响远比对与多巴胺转运蛋白的相互作用的影响更显着。
• [EN] DIAZABICYCLONONENE AND TETRAHYDROPYRIDINE DERIVATIVES AS RENIN INHIBITORS<br/>[FR] DERIVES DE DIAZABICYCLONONENE ET DE TETRAHYDROPYRIDINE UTILISES COMME INHIBITEURS DE LA RENINE
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2005040173A1

  公开（公告）日：2005-05-06

  The invention relates to novel bicyclic derivatives and related compounds and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as inhibitors of renin.

  本发明涉及新型的双环衍生物及相关化合物，以及它们作为活性成分在制备药物组合物中的应用。本发明还涉及相关方面，包括制备这些化合物的方法、含有一种或多种这些化合物的药物组合物，尤其是它们作为肾素抑制剂的应用。
• [EN] TROPANE DERIVATIVES AND THEIR USE AS ACE INHIBITORS<br/>[FR] DERIVES DE TROPANE ET LEUR UTILISATION COMME INHIBITEURS D'ACE
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2004096799A1

  公开（公告）日：2004-11-11

  The invention relates to novel tropane derivatives and related compounds and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as inhibitors of renin.

  本发明涉及新型的莨菪衍生物及相关化合物，以及它们作为活性成分在制备药物组合物中的用途。本发明还涉及相关方面，包括制备这些化合物的过程，含有一种或多种这些化合物的药物组合物，尤其是它们作为肾素抑制剂的用途。
• Synthesis and Ligand Binding of Tropane Ring Analogues of Paroxetine
  作者：Kathryn I. Keverline-Frantz、John W. Boja、Michael J. Kuhar、Philip Abraham、Jason P. Burgess、Anita H. Lewin、F. Ivy Carroll

  DOI：10.1021/jm970669p

  日期：1998.1.1

  binding were not the (1R)-2 beta, 3 beta-isomers but rather (1R)-2 beta, 3 alpha-4c and (1S)-2 beta, 3 alpha-4f. Conformational analyses show that these isomers exist in a flattened boat conformation with pseudoequatorial substituents. Thus, the binding data show that this conformation is recognized by the DAT-associated binding site and also suggest that this conformation of paroxetine is recognized by

  （3S，4R）-4-（4-氟苯基）-3-[[3,4-（亚甲基二氧基）苯氧基]甲基]哌啶[（3S，9R）-3，帕罗西汀]是选择性5-羟色胺再摄取抑制剂（SSRI）在人类中用作抗抑郁药。在以前的研究中，我们报道了某些（1R）-3β-（取代的苯基）降冰片烷2β-羧酸甲酯（2a）对5-羟色胺转运蛋白（5-HTT）表现出高亲和力和合理的选择性。2a和（3S，4R）-3之间的主要结构差异是2a具有不同的绝对立体化学，并具有3中不存在的亚乙基桥。此外，2a具有与芳基环相邻的碳甲氧基取代基，而（3S， 4R）-3含有[3，4-（亚甲基二氧基）苯氧基]甲基。在这项研究中，我们介绍了3-（4-氟苯基）-2-[[3，4-（亚甲基二氧基）苯氧基]甲基]降冰片烷++（4）。抑制[3H]帕罗西汀结合的数据表明，具有与帕罗西汀相同的立体化学的（1R）-2 beta，3 alpha-4c对5-HTT具有最高的亲和力。令人惊讶的是，抑制[3H]