1-(5-phenylethynyl-furan-2-yl)carbonyl-5'-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-spiro[piperidine-4,3'-(2H)-benzo[b]furan] | 1025688-04-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 1-(5-phenylethynyl-furan-2-yl)carbonyl-5'-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-spiro[piperidine-4,3'-(2H)-benzo[b]furan]
• 英文别名: 2-[[1'-[5-(2-phenylethynyl)furan-2-carbonyl]spiro[2H-1-benzofuran-3,4'-piperidine]-5-yl]methyl]isoindole-1,3-dione
• CAS: 1025688-04-3
• 化学式: C₃₄H₂₆N₂O₅
• 分子量: 542.591
• InChiKey: OUNWNQRBHWZDGZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  41
• 可旋转键数：
  5
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  80.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(5-phenylethynyl-furan-2-yl)carbonyl-5'-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-spiro[piperidine-4,3'-(2H)-benzo[b]furan] 在 甲基肼 作用下， 以 乙醇 为溶剂， 生成 JNJ-27390467 free base
  参考文献：
  名称：

  Potent, nonpeptide inhibitors of human mast cell tryptase. Synthesis and biological evaluation of novel spirocyclic piperidine amide derivatives

  摘要：

  We have explored a series of spirocyclic piperidine amide derivatives ( 5) as tryptase inhibitors. Thus, 4 (JNJ-27390467) was identified as a potent, selective tryptase inhibitor with oral efficacy in two animal models of airway inflammation ( sheep and guinea pig asthma models). An X-ray co-crystal structure of 4 tryptase revealed a hydrophobic pocket in the enzyme's active site, which is induced by the phenylethynyl group and is comprised of amino acid residues from two different monomers of the tetrameric protein. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.01.093
• 作为产物：
  描述：

  5-(2-苯基乙-1-炔基)-2-呋喃甲酸 、 5'-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-spiro[piperidine-4,3'-benzo[b]furan] hydrochloride 在 双(2-氧代-3-恶唑烷基)次磷酰氯 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.25h， 以99%的产率得到1-(5-phenylethynyl-furan-2-yl)carbonyl-5'-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-spiro[piperidine-4,3'-(2H)-benzo[b]furan]
  参考文献：
  名称：

  [EN] SPIROPIPERIDINES FOR USE AS TRYPTASE INHIBITORS
  [FR] SPIROPIPÉRIDINES UTILISABLES EN TANT QU'INHIBITEURS DE LA TRYPTASE

  摘要：

  本发明涉及一种化合物，其化学式为（I）：（I）或其形式，其中X1、X2、X3、X4、R1、R2和R3如本文所定义，可用作色氨酸蛋白酶抑制剂。

  公开号：

  WO2009067202A1

文献信息

• [EN] SPIROPIPERIDINES FOR USE AS TRYPTASE INHIBITORS<br/>[FR] SPIROPIPÉRIDINES UTILISABLES EN TANT QU'INHIBITEURS DE LA TRYPTASE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2009067202A1

  公开（公告）日：2009-05-28

  The present invention is directed to a compound of Formula (I): (I) or a form thereof, wherein X1, X2, X3, X4, R1, R2 and R3 are as defined herein, useful as tryptase inhibitors.

  本发明涉及一种化合物，其化学式为（I）：（I）或其形式，其中X1、X2、X3、X4、R1、R2和R3如本文所定义，可用作色氨酸蛋白酶抑制剂。
• SPIROPIPERIDINES FOR USE AS TRYPTASE INHIBITORS
  申请人：Janssen Pharmaceutica N.V.

  公开号：EP2224803A1

  公开（公告）日：2010-09-08
• US8158792B2
  申请人：——

  公开号：US8158792B2

  公开（公告）日：2012-04-17
• Potent, nonpeptide inhibitors of human mast cell tryptase. Synthesis and biological evaluation of novel spirocyclic piperidine amide derivatives
  作者：Michael J. Costanzo、Stephen C. Yabut、Han-Cheng Zhang、Kimberley B. White、Lawrence de Garavilla、Yuanping Wang、Lisa K. Minor、Brett A. Tounge、Alexander N. Barnakov、Frank Lewandowski、Cynthia Milligan、John C. Spurlino、William M. Abraham、Victoria Boswell-Smith、Clive P. Page、Bruce E. Maryanoff

  DOI：10.1016/j.bmcl.2008.01.093

  日期：2008.3

  We have explored a series of spirocyclic piperidine amide derivatives ( 5) as tryptase inhibitors. Thus, 4 (JNJ-27390467) was identified as a potent, selective tryptase inhibitor with oral efficacy in two animal models of airway inflammation ( sheep and guinea pig asthma models). An X-ray co-crystal structure of 4 tryptase revealed a hydrophobic pocket in the enzyme's active site, which is induced by the phenylethynyl group and is comprised of amino acid residues from two different monomers of the tetrameric protein. (c) 2008 Elsevier Ltd. All rights reserved.