(+/-)-methyl endo-7-(tert-butoxycarbonyl)-7-azabicyclo[2.2.1]heptane-2-carboxylate

• 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: (+/-)-methyl endo-7-(tert-butoxycarbonyl)-7-azabicyclo[2.2.1]heptane-2-carboxylate
• 英文别名: methyl 7-(tert-butoxycarbonyl)-7-azabicyclo[2.2.1]heptane-2-carboxylate；7-tert-butyl 2-methyl endo-7-azabicyclo[2.2.1]heptane-7-carboxylate；7-tert-butyl 2-methyl 7-azabicyclo[2.2.1]heptane-2,7-dicarboxylate；(+/-) endo-7-tert-butyl 2-methyl 7-azabicyclo[2.2.1]heptane-2,7-dicarboxylate；(+/-)-endo-7-tert-butyl-2-methyl-7-azabicyclo[2.2.1]heptane-2,7-dicarboxylate；7-O-tert-butyl 2-O-methyl (1R,2R,4S)-7-azabicyclo[2.2.1]heptane-2,7-dicarboxylate
• 化学式: C₁₃H₂₁NO₄
• 分子量: 255.314
• InChiKey: ZBESKVIRYNQXCD-IVZWLZJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+/-)-methyl endo-7-(tert-butoxycarbonyl)-7-azabicyclo[2.2.1]heptane-2-carboxylate 在 4-二甲氨基吡啶 、 lithium hydroxide 、 草酰氯 、 sodium hydride 、 sodium carbonate 、 N,N-二甲基甲酰胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 66.5h， 生成 7-Azabicyclo[2.2.1]heptane-2,7-dicarboxylic acid,7-(9H-fluoren-9-ylmethyl) 2-(phenylmethyl) ester, (1R,2R,4S)-
  参考文献：
  名称：

  Oligomers of β-amino acid bearing non-planar amides form ordered structures

  摘要：

  In this report, we explore the feasibility of using bicyclic chiral beta-amino acids, (1R,2R,4S)- and (1S,2S,4R)-7-azabicyclo[2.2.1]-heptane-2-carboxylic acid (R-Ah2c and S-Ah2c, respectively), to prepare novel peptides with unique properties. Facile cis-trans isomerization of the non-planar amide bonds of these beta-amino acids should result in great flexibility of the backbone structure of beta-peptides containing them. Indeed, oligomers of these amino acids showed thermostability and characteristic CD absorptions, which were not concentration-dependent, suggesting that the oligomers remained monomeric. The results indicated the formation of self-organized monomeric structures with chain-length-dependent stabilization. Energy calculations suggested that the peptides can take helical structures in which the energy barriers to cis-trans isomerization are greater for the central amide bonds than for the terminal amides. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2006.09.062
• 作为产物：
  描述：

  1-吡咯甲酸叔丁酯 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 甲醇 为溶剂， 90.0~95.0 ℃ 、101.33 kPa 条件下， 反应 30.0h， 生成 (+/-)-methyl endo-7-(tert-butoxycarbonyl)-7-azabicyclo[2.2.1]heptane-2-carboxylate
  参考文献：
  名称：

  Cheng; Izenwasser; Wade, Medicinal Chemistry Research, 2001, vol. 10, # 6, p. 356 - 365

  摘要：

  DOI：

文献信息

• Design, synthesis, structure–activity relationship, and in vivo activity of azabicyclic aryl amides as α7 nicotinic acetylcholine receptor agonists
  作者：Daniel P. Walker、Donn G. Wishka、David W. Piotrowski、Shaojuan Jia、Steven C. Reitz、Karen M. Yates、Jason K. Myers、Tatiana N. Vetman、Brandon J. Margolis、E. Jon Jacobsen、Brad A. Acker、Vincent E. Groppi、Mark L. Wolfe、Bruce A. Thornburgh、Paula M. Tinholt、Luz A. Cortes-Burgos、Rodney R. Walters、Matthew R. Hester、Eric P. Seest、Lester A. Dolak、Fusen Han、Barbara A. Olson、Laura Fitzgerald、Brian A. Staton、Thomas J. Raub、Mihaly Hajos、William E. Hoffmann、Kai S. Li、Nicole R. Higdon、Theron M. Wall、Raymond S. Hurst、Erik H.F. Wong、Bruce N. Rogers

  DOI：10.1016/j.bmc.2006.09.019

  日期：2006.12

  A novel set of azabicyclic aryl amides have been identified as potent and selective agonists of the alpha7 nAChR. A two-pronged approach was taken to improve the potential hERG liability of previously disclosed alpha7 nAChR agonist, PNU-282,987, while maintaining the compound's other desirable pharmacological properties. The first approach involved further exploration of the aryl carboxylic acid fragment

  一组新的氮杂双环芳基酰胺已被鉴定为α7nAChR的有效和选择性激动剂。采取了两管齐下的方法来改善先前公开的alpha7 nAChR激动剂PNU-282,987的潜在hERG耐受性，同时保持该化合物的其他所需药理特性。第一种方法涉及对PNU-282,987的芳基羧酸片段的进一步研究，而第二种方法则侧重于对PNU-282,987的氮杂双环胺部分的修饰。每个系列中最好的化合物的特点是脑部快速渗透，在大鼠中具有良好的口服生物利用度，并在大鼠P50听觉感觉门控试验中显示出体内功效。每个系列（1h，1o，2a，9a和18a）中至少有一个类似物表现出比PNU-282,987更高的hERG安全性。
• COMPOUNDS AND USES THEREOF FOR THE MODULATION OF HEMOGLOBIN
  申请人：Global Blood Therapeutics, Inc.

  公开号：US20150141465A1

  公开（公告）日：2015-05-21

  Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.

  本文提供了适用作为血红蛋白调节剂的化合物和药物组合物，它们的制备方法和中间体，以及在治疗由血红蛋白介导的疾病和需要组织和/或细胞氧合的疾病中使用它们的方法。
• [EN] 1H-PYRAZOLE AND 1H-PYRROLE-AZABICYCLIC COMPOUNDS WITH ALFA-7 NACHR ACTIVITY<br/>[FR] COMPOSES AZABICYCLIQUE DE 1H-PYRAZOLE ET 1H-PYRROLE SERVANT A EFFECTUER UN TRAITEMENT THERAPEUTIQUE
  申请人：UPJOHN CO

  公开号：WO2004013137A1

  公开（公告）日：2004-02-12

  The invention provides compounds of Formula (I), wherein Azabicyclo is Formula (I, II, III, IV, V, VI, VII); W is Formula (m); where the variables have the definitions discussed herein. These compounds may be in the form of pharmaceutical salts or compositions, may be in pure enantiomeric form or racemic mixtures, and are useful in pharmaceuticals to treat a disease or condition in which α7 is known to be involved.

  这项发明提供了Formula (I)的化合物，其中Azabicyclo是Formula (I, II, III, IV, V, VI, VII); W是Formula (m); 其中变量的定义如本文所述。这些化合物可以是药用盐或组合物的形式，可以是纯对映体形式或混合物，对于治疗已知涉及α7的疾病或症状的药物具有用处。
• Visible-Light-Triggered Release of Nitric Oxide from N-Pyramidal Nitrosamines
  作者：Fumika Karaki、Yoji Kabasawa、Takahiro Yanagimoto、Nobuhiro Umeda、Firman、Yasuteru Urano、Tetsuo Nagano、Yuko Otani、Tomohiko Ohwada

  DOI：10.1002/chem.201101427

  日期：2012.1.23

  many organic/inorganic compounds that release nitric oxide (NO) upon photoirradiation (phototriggered caged‐NOs) have been reported, their photoabsorption wavelengths mostly lie in the UV region, because XNO bonds (X=heteroatom and metal) generally have rather strong π‐bond character. Thus, it is intrinsically difficult to generate organic compounds that release NO under visible light irradiation. Herein

  虽然（phototriggered笼-NOS）已经被报道，释放一氧化氮（NO）在光照射许多有机/无机化合物，它们的光吸收波长大多位于紫外区，因为X  NO键（X =杂原子和金属）通常具有相当强大的π键性格。因此，本质上难以产生在可见光照射下释放NO的有机化合物。在此，描述了在可见光照射下释放NO的7-氮杂双环[2.2.1]庚烷的N-锥体亚硝胺衍生物的结构和性质。这些亚硝胺的吸收的红移，这归因于HOMO（N）-LUMO（π*）与N的非平面结构相关联的过渡NO部分使分子能够吸收可见光，从而导致NNO键断裂。因此，这些化合物是先天性有机笼状NO，不会被可见光束缚。
• [EN] COMPOUNDS AS RADIOLIGANDS FOR THE DIAGNOSIS OF DISEASE<br/>[FR] COMPOSES UTILISES COMME LIGANDS RADIOACTIFS POUR DIAGNOSTIQUER UNE MALADIE
  申请人：UPJOHN CO

  公开号：WO2004052889A1

  公开（公告）日：2004-06-24

  Radiolabeled ligands useful as probes for determining the relative abundance, receptor occupancy, and/or function of nicotinic acetylcholine receptors. The compounds of Formula I as described herein are labeled with a radioactive isotopic moiety such as 11C, 18F, 76Br, 123I or 125I. Disorders are diagnosed by administering to a mammal a detectably labeled compound and detecting the binding of that compound to the nAChR. The compounds that have been administered are detected using methods including, but not limited to, position emission topography and single-photon to emission computed tomography. The present invention is useful in diagnosing a wide variety of diseases and disorders as discussed herein.

  放射性标记的配体可用作探针，用于确定尼古丁乙酰胆碱受体的相对丰度、受体占有率和/或功能。本文描述的式I化合物标记有放射性同位素基团，如11C、18F、76Br、123I或125I。通过向哺乳动物注射可检测标记的化合物，并检测该化合物与nAChR的结合来诊断疾病。已经注射的化合物可使用包括但不限于正电子发射断层扫描和单光子发射计算机断层扫描在内的方法进行检测。本发明在诊断各种疾病和障碍方面具有实用性，如本文所述。