((1R)-1-{5-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-3-fluoropyridin-2-yl}ethyl)amine | 864710-29-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: ((1R)-1-{5-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-3-fluoropyridin-2-yl}ethyl)amine
• 英文别名: (R)-1-{5-[3,5-dichloro-2-(2,2-difluoro-ethoxy)-phenyl]-3-fluoro-pyridin-2-yl}-ethylamine；2-[(R)-1-Aminoethyl]-3-fluoro-5-[2-(2,2-difluoroethoxy)-3,5-dichlorophenyl]pyridine；(1R)-1-[5-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-3-fluoropyridin-2-yl]ethanamine
• CAS: 864710-29-2
• 化学式: C₁₅H₁₃Cl₂F₃N₂O
• 分子量: 365.182
• InChiKey: DRSCUBFQVHMJRK-SSDOTTSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  48.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ((1R)-1-{5-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-3-fluoropyridin-2-yl}ethyl)amine 、 Boc-1-氨基环丙基甲酸 在 N-羟基-7-氮杂苯并三氮唑 、 TEA 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 tert-butyl 1-{[((1R)-1-{5-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-3-fluoropyridin-2-yl}ethyl)amino]carbonyl}cyclopropyl carbamate
  参考文献：
  名称：

  A new class of bradykinin B1 receptor antagonists with high oral bioavailability and minimal PXR activity

  摘要：

  The design and synthesis of a novel class of human bradykinin B, antagonists featuring difluoroethyl ether and isoxazole carboxamide moieties are disclosed. Compound 7g displayed excellent pharmacokinetic properties, efficient ex vivo receptor occupancy, and low potential for P450 induction via PXR activation. (c) 2008 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2007.11.057
• 作为产物：
  描述：

  (R)-N-((R)-1-(5-(3,5-dichloro-2-(2,2-difluoroethoxy)phenyl)-3-fluoropyridin-2-yl)ethyl)-2-methylpropane-2-sulfinamide 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 ((1R)-1-{5-[3,5-dichloro-2-(2,2-difluoroethoxy)phenyl]-3-fluoropyridin-2-yl}ethyl)amine
  参考文献：
  名称：

  A new class of bradykinin B1 receptor antagonists with high oral bioavailability and minimal PXR activity

  摘要：

  The design and synthesis of a novel class of human bradykinin B, antagonists featuring difluoroethyl ether and isoxazole carboxamide moieties are disclosed. Compound 7g displayed excellent pharmacokinetic properties, efficient ex vivo receptor occupancy, and low potential for P450 induction via PXR activation. (c) 2008 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2007.11.057

文献信息

• [EN] NEW BIARYL AMIDE DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS DE BIARYLAMIDE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012089601A1

  公开（公告）日：2012-07-05

  The invention provides novel compounds having the general formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12 and A are as described herein, compositions including the compounds and methods of using the compounds.

  这项发明提供了具有通式（I）的新化合物，其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12和A如本文所述，包括这些化合物的组合物以及使用这些化合物的方法。
• NEW BIARYL AMIDE DERIVATIVES
  申请人：Aebi Johannes

  公开号：US20120165338A1

  公开（公告）日：2012-06-28

  The invention provides novel compounds having the general formula (I) wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and A are as described herein, compositions including the compounds and methods of using the compounds.

  这项发明提供了具有一般式（I）的新化合物，其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12和A如本文所述，包括这些化合物的组合物以及使用这些化合物的方法。
• Biaryl amide derivatives
  申请人：Aebi Johannes

  公开号：US08912221B2

  公开（公告）日：2014-12-16

  The invention provides novel compounds having the general formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12 and A are as described herein, compositions including the compounds and methods of using the compounds.

  本发明提供了一种具有一般式(I)的新化合物，其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12和A如本文所述，包括该化合物的组合物和使用该化合物的方法。
• Practical Synthesis of a Potent Bradykinin B₁ Antagonist via Enantioselective Hydrogenation of a Pyridyl <i>N</i>-Acyl Enamide
  作者：Paul D. O’Shea、Danny Gauvreau、Francis Gosselin、Greg Hughes、Christian Nadeau、Amélie Roy、C. Scott Shultz

  DOI：10.1021/jo802772d

  日期：2009.6.19

  A practical and efficient synthesis of bradykinin B I antagonist I is described. A convergent strategy was utilized which involved synthesis of three fragments: 3, 6, and 7. Cross coupling of fragments 6 and 7 followed by amidation with 3 enabled efficient synthesis of I in 19 steps total, a 35% overall yield from commercially available pyridine 10. The key to the success of the synthesis was the development of a fluorodenitration step to install the fluorine in pyridine 7 and a catalytic enantioselective hydrogenation of N-acyl enamide 9 to set the stereochemistry.
• Novel small molecule bradykinin B1 receptor antagonists. Part 1: Benzamides and semicarbazides
  作者：Marco Schaudt、Elsa Locardi、Gunther Zischinsky、Roland Stragies、Jochen R. Pfeifer、Christoph Gibson、Dirk Scharn、Uwe Richter、Holger Kalkhof、Klaus Dinkel、Karsten Schnatbaum

  DOI：10.1016/j.bmcl.2009.11.119

  日期：2010.2

  The synthesis and SAR of two series of bradykinin B-1 receptor antagonists is described. The benzamide moiety proved to be a suitable replacement for the aryl ester functionality of biaryl based antagonists. In addition, it was found that semicarbazides can effectively replace cyclopropyl amino acids. The compounds with the best overall pro. le were biaryl semicarbazides which display high antagonistic activity, low Caco-2 efflux and high oral bioavailability in the rat. (C) 2009 Elsevier Ltd. All rights reserved.