1-(2-phenylethyl)-8-Boc-1,3,8-triazaspiro[4.5]dec-2-en-4-one | 288154-21-2

• 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]dec-2-en-4-one
• 英文别名: Tert-butyl 4-oxo-1-(2-phenylethyl)-1,3,8-triazaspiro[4.5]dec-2-ene-8-carboxylate
• CAS: 288154-21-2
• 化学式: C₂₀H₂₇N₃O₃
• 分子量: 357.453
• InChiKey: MTVPXDHJBWWAED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  62.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-phenylethyl)-8-Boc-1,3,8-triazaspiro[4.5]dec-2-en-4-one 在 盐酸 、 sodium tetrahydroborate 、 sodium hydride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.25h， 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：

  A Rational Approach to the Design and Synthesis of a New Bradykinin B₁ Receptor Antagonist

  摘要：

  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of this potent B1 bradykinin receptor antagonist in which the central Pro(2)-Hyp(3)-Gly(4)-Igl(5) tetrapeptide has been replaced by constrained N-1-substituted-1,3,8-triazaspirol[4.5]decan-4-one ring system were synthesized.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.

  DOI：

  10.1021/jm990962k
• 作为产物：
  描述：

  4-氨基-1-boc-哌啶-4-羧酰胺 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 16.0h， 生成 1-(2-phenylethyl)-8-Boc-1,3,8-triazaspiro[4.5]dec-2-en-4-one
  参考文献：
  名称：

  A Rational Approach to the Design and Synthesis of a New Bradykinin B₁ Receptor Antagonist

  摘要：

  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.

  DOI：

  10.1021/jm990962k

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.