1-(2-phenylethyl)-8-Boc-1,3,8-triazaspiro[4.5]decan-4-one-3-acetic acid | 180386-40-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: 1-(2-phenylethyl)-8-Boc-1,3,8-triazaspiro[4.5]decan-4-one-3-acetic acid
• 英文别名: 8-[(1,1-Dimethylethoxy)carbonyl]-4-oxo-1-(2-phenylethyl)-1,3,8-triazaspiro[4.5]decane-3-acetic acid；2-[8-[(2-methylpropan-2-yl)oxycarbonyl]-4-oxo-1-(2-phenylethyl)-1,3,8-triazaspiro[4.5]decan-3-yl]acetic acid
• CAS: 180386-40-7
• 化学式: C₂₂H₃₁N₃O₅
• 分子量: 417.505
• InChiKey: MSOFRAVVAPEZBG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  90.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-叔丁氧羰基-N'-甲苯磺酰基-L-精氨酸 、 BOC-对甲基苯磺酰-D-精氨酸 、 叔丁氧羰基-L-八氢化吲哚-2-羧酸 、 1-(2-phenylethyl)-8-Boc-1,3,8-triazaspiro[4.5]decan-4-one-3-acetic acid 、 alkaline earth salt of/the/ methylsulfuric acid 生成
  参考文献：
  名称：

  Synthesis and Characterization of Pseudopeptide Bradykinin B2 Receptor Antagonists Containing the 1,3,8-Triazaspiro[4.5]decan-4-one Ring System

  摘要：

  A series of pseudopeptides containing alkyl-, cycloalkyl-, aryl-, and aralkyl-substituted 1,3,8-triazaspiro[4.5]decan-4-one-3-acetic acids as amino acid surrogates to replace the Pro(2)-Pro(3)-Gly(4)-Phe(5) section of the peptide bradykinin B2 receptor antagonist [Pro(3), Phe(5)]HOE 140 (D-Arg(0)-Arg(1)-Pro(2)-Pro(3)-Gly(4)-Phe(5)-Ser(6)-D-Tic(7)-Oic(8)-Arg(9)) were prepared. These psuedopeptides were examined in vitro for their B2 receptor affinities as well as for their ability to block bradykinin mediated actions in, vivo. Two compounds in particular, NPC 18521 (I) and NPC 18688 (V) were quite potent in these latter assays, indicating that a significant portion of this prototypical second generation decapeptide antagonist can be replaced with a more compact nonpeptide molecule.

  DOI：

  10.1021/jm950676i
• 作为产物：
  描述：

  1-Benzyl-4-(phenethylamino)piperidine-4-carbonitrile 在 palladium on activated charcoal 盐酸 、 硫酸 、 氢气 、 sodium hydride 、 sodium carbonate 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 甲苯 为溶剂， 25.0 ℃ 、310.27 kPa 条件下， 反应 162.5h， 生成 1-(2-phenylethyl)-8-Boc-1,3,8-triazaspiro[4.5]decan-4-one-3-acetic acid
  参考文献：
  名称：

  Synthesis and Characterization of Pseudopeptide Bradykinin B2 Receptor Antagonists Containing the 1,3,8-Triazaspiro[4.5]decan-4-one Ring System

  摘要：

  A series of pseudopeptides containing alkyl-, cycloalkyl-, aryl-, and aralkyl-substituted 1,3,8-triazaspiro[4.5]decan-4-one-3-acetic acids as amino acid surrogates to replace the Pro(2)-Pro(3)-Gly(4)-Phe(5) section of the peptide bradykinin B2 receptor antagonist [Pro(3), Phe(5)]HOE 140 (D-Arg(0)-Arg(1)-Pro(2)-Pro(3)-Gly(4)-Phe(5)-Ser(6)-D-Tic(7)-Oic(8)-Arg(9)) were prepared. These psuedopeptides were examined in vitro for their B2 receptor affinities as well as for their ability to block bradykinin mediated actions in, vivo. Two compounds in particular, NPC 18521 (I) and NPC 18688 (V) were quite potent in these latter assays, indicating that a significant portion of this prototypical second generation decapeptide antagonist can be replaced with a more compact nonpeptide molecule.

  DOI：

  10.1021/jm950676i

文献信息

• A Rational Approach to the Design and Synthesis of a New Bradykinin B₁ Receptor Antagonist
  作者：Philippe Bedos、Muriel Amblard、Gilles Subra、Pierre Dodey、Jean-Michel Luccarini、Jean-Luc Paquet、Didier Pruneau、André Aumelas、Jean Martinez

  DOI：10.1021/jm990962k

  日期：2000.6.1

  We have previously synthesized a potent and selective B-1 bradykinin receptor antagonist, JMV1645 (H-Lys-Arg-Pro-Hyp-Gly-Igl-Ser-D-BT-OH), containing a dipeptide mimetic ((3S)-amino-5-carbonylmethyl-2,3-dihydro-1,5-benzothiazepin-4(5H)-one (D-BT) moiety) at the C-terminal. Analogues of this potent B1 bradykinin receptor antagonist in which the central Pro(2)-Hyp(3)-Gly(4)-Igl(5) tetrapeptide has been replaced by constrained N-1-substituted-1,3,8-triazaspirol[4.5]decan-4-one ring system were synthesized. Among these analogues, compound JMV1640 (1) was found to have an affinity of 24.10 +/- 9.48 nM for the human cloned B-1 receptor. It antagonized the [des-Arg(10)]-kallidin-induced contraction of the human umbilical vein (pA(2) = 6.1 +/- 0.1). Compound 1 was devoid of agonist activity at the kinin B-1 receptor. Moreover, it did not bind to the human cloned B-2 receptor. Therefore, JMV1640 constitutes a lead compound for the rational search of nonpeptide B-1 receptor analogues based on the BK sequence.
• Synthesis and Characterization of Pseudopeptide Bradykinin B2 Receptor Antagonists Containing the 1,3,8-Triazaspiro[4.5]decan-4-one Ring System
  作者：Babu J. Mavunkel、Zhijian Lu、R. Richard Goehring、Songfeng Lu、Sarvajit Chakravarty、John Perumattam、Elizabeth A. Novotny、Maureen Connolly、Heather Valentine、Donald J. Kyle

  DOI：10.1021/jm950676i

  日期：1996.1.1

  A series of pseudopeptides containing alkyl-, cycloalkyl-, aryl-, and aralkyl-substituted 1,3,8-triazaspiro[4.5]decan-4-one-3-acetic acids as amino acid surrogates to replace the Pro(2)-Pro(3)-Gly(4)-Phe(5) section of the peptide bradykinin B2 receptor antagonist [Pro(3), Phe(5)]HOE 140 (D-Arg(0)-Arg(1)-Pro(2)-Pro(3)-Gly(4)-Phe(5)-Ser(6)-D-Tic(7)-Oic(8)-Arg(9)) were prepared. These psuedopeptides were examined in vitro for their B2 receptor affinities as well as for their ability to block bradykinin mediated actions in, vivo. Two compounds in particular, NPC 18521 (I) and NPC 18688 (V) were quite potent in these latter assays, indicating that a significant portion of this prototypical second generation decapeptide antagonist can be replaced with a more compact nonpeptide molecule.