(R)-tert-butyl (6-(iodomethyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate | 883997-62-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (R)-tert-butyl (6-(iodomethyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate
• 英文别名: (R)-tert-butyl 6-(iodomethyl)-1,2,3,4-tetrahydronaphthalen-1-yl-carbamate；(R)-tert-butyl 6-(iodomethyl)-1,2,3,4-tetrahydronaphthalen-1-ylcarbamate；tert-butyl N-[(1R)-6-(iodomethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]carbamate
• CAS: 883997-62-4
• 化学式: C₁₆H₂₂INO₂
• 分子量: 387.261
• InChiKey: VUVDWAJHLXPSPO-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-tert-butyl (6-(iodomethyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 在 potassium carbonate 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 6.0h， 生成 (R)-N-(1-((5-amino-5,6,7,8-tetrahydronaphthalen-2-yl)methyl)piperidin-4-yl)-N-phenylpropionamide trifluoroacetate
  参考文献：
  名称：

  发现 5-取代四氢萘-2基-甲基与 N-苯基-N-(哌啶-4-基)丙酰胺衍生物作为有效的阿片受体配体

  摘要：

  基于含有5-取代四氢萘-2基)甲基的4-苯胺哌啶支架和不同的N-苯基-N- (哌啶-4-基)丙酰胺衍生物，设计并合成了一系列新型阿片配体，以研究其这些取代基对 μ 和 δ 阿片受体相互作用的生物学影响。最近，我们课题组报道了新型4-苯胺哌啶类似物，其中几个含有芳香环的氨基酸与N-苯基-N- (哌啶-4-基)丙酰胺缀合，并检测了它们对μ和δ阿片受体的生物活性。为了继续我们在这些新型4-苯胺哌啶类似物方面的努力，我们在本设计中采用了肽模拟方法，其中我们用四氢萘-2基甲基部分取代了芳香族氨基酸，并在第5位上进行了氨基、酰胺和羟基取代。在体外测定中，这些配体显示出非常好的结合亲和力和对μ阿片受体的高度选择性。其中，先导配体20对 μ 阿片受体表现出优异的结合亲和力 (2 nM) 和 5000 倍的选择性，以及 GPI 测定中的功能选择性 (55.20 ± 4.30 nM) 和 MVD 测定中的弱或

  DOI：

  10.1016/j.bmc.2015.07.071
• 作为产物：
  描述：

  (R)-tert-butyl 6-(hydroxymethyl)-1,2,3,4-tetrahydronaphthalen-1-ylcarbamate 在 咪唑 、 碘 、 三苯基膦 作用下， 以 乙醚 、 1,2-二氯乙烷 为溶剂， 反应 0.33h， 生成 (R)-tert-butyl (6-(iodomethyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate
  参考文献：
  名称：

  [EN] SUBSTITUTED SULFONAMIDOPROPIONAMIDES AND METHODS OF USE
  [FR] SULFONAMIDOPROPIONAMIDES SUBSTITUES ET PROCEDES D'UTILISATION

  摘要：

  这项发明属于药物代理领域，具体涉及化合物、组合物、用途和治疗与炎症相关的疾病，包括疼痛的方法。

  公开号：

  WO2006036664A1

文献信息

• 1,2,3,4-Tetrahydropyrazin-2-yl acetamides and methods of use
  申请人：Askew C. Benny

  公开号：US20060025400A1

  公开（公告）日：2006-02-02

  Selected compounds are effective for treatment of pain and diseases, such as inflammation mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable derivatives thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving pain, inflammation, and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

  所选化合物对于治疗疼痛和疾病，如炎症介导的疾病，具有有效性。该发明涵盖了新颖的化合物、类似物、前药和其药学上可接受的衍生物，药物组合物以及用于预防和治疗涉及疼痛、炎症等疾病和其他不适或情况的方法。该发明还涉及制备此类化合物的方法，以及在此类过程中有用的中间体。
• Substituted sulfones and methods of use
  申请人：Askew C. Benny

  公开号：US20060111347A1

  公开（公告）日：2006-05-25

  Selected compounds are effective for treatment of pain and diseases, such as inflammation mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable derivatives thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving pain, inflammation, and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

  所选化合物对于治疗疼痛和炎症介导的疾病有效。本发明涵盖新颖的化合物、类似物、前药和其药学上可接受的衍生物、制备这些化合物的药物组合物以及预防和治疗涉及疼痛、炎症等疾病和其他不适或病况的方法。本发明还涉及制备这些化合物的过程，以及在这些过程中有用的中间体。
• [EN] SUBSTITUTED ARYL OR HETEROARYLSULFONYLBUTANAMIDES FOR USE AS ANTI-INFLAMMATORY AGENTS<br/>[FR] SULFONES SUBSTITUES ET LEURS METHODES D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2006041888A3

  公开（公告）日：2007-09-07
• Aryl sulfonamides containing tetralin allylic amines as potent and selective bradykinin B1 receptor antagonists
  作者：Qingyian Liu、Wenyuan Qian、Aiwen Li、Kaustav Biswas、Jian Jeffrey Chen、Christopher Fotsch、Nianhe Han、Chester Yuan、Leyla Arik、Gloria Biddlecome、Eileen Johnson、Gondi Kumar、Dianna Lester-Zeiner、Gordon Y. Ng、Randall W. Hungate、Benny C. Askew

  DOI：10.1016/j.bmcl.2010.06.010

  日期：2010.8

  The bradykinin B1 receptor has been shown to mediate pain response and is rapidly induced upon injury. Blocking this receptor may provide a promising treatment for inflammation and pain. We previously reported tetralin benzyl amines as potent B1 antagonists. Here we describe the synthesis and SAR of B1 receptor antagonists with homobenzylic amines. The SAR of different linkers led to the discovery of tetralin allylic amines as potent and selective B1 receptor antagonists (hB1 IC(50) = 1.3 nM for compound 16). Some of these compounds showed modest oral bioavailability in rats. (C) 2010 Elsevier Ltd. All rights reserved.
• Design synthesis and structure–activity relationship of 5-substituted (tetrahydronaphthalen-2yl)methyl with N-phenyl-N-(piperidin-2-yl)propionamide derivatives as opioid ligands
  作者：Srinivas Deekonda、David Rankin、Peg Davis、Josephine Lai、Todd. W. Vanderah、Frank Porecca、Victor J. Hruby

  DOI：10.1016/j.bmc.2015.11.030

  日期：2016.1

  Here, we report the design, synthesis and structure activity relationship of novel small molecule opioid ligands based on 5-amino substituted (tetrahydronaphthalen-2-yl)methyl moiety with N-phenyl-N-(piperidin-2-yl)propionamide derivatives. We synthesized various molecules including amino, amide and hydroxy substitution on the 5th position of the (tetrahydronaphthalen-2-yl) methyl moiety. In our further designs we replaced the (tetrahydronaphthalen-2-yl)methyl moiety with benzyl and phenethyl moiety. These N-phenyl-N-(piperidin-2-yl)propionamide analogues showed moderate to good binding affinities (850-4 nM) and were selective towards the mu opioid receptor over the delta opioid receptors. From the structure activity relationship studies, we found that a hydroxyl substitution at the 5th position of (tetrahydronapthalen-2yl)methyl group, ligands 19 and 20, showed excellent binding affinities 4 and 5 nM, respectively, and 1000 fold selectivity towards the mu opioid relative to the delta opioid receptor. The ligand 19 showed potent agonist activities 75 +/- 21 nM, and 190 +/- 42 nM in the GPI and MVD assays. Surprisingly the fluoro analogue 20 showed good agonist activities in MVD assays 170 +/- 42 nM, in contrast to its binding affinity results. (C) 2015 Elsevier Ltd. All rights reserved.