(+/-) cis-2-butyl-5-(3-pyridinyl)-5,6,11,11a-tetrahydro-1H-imidazo[1',5':1,6]pyrido[3,4-b]indole-1,3(2H)-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (+/-) cis-2-butyl-5-(3-pyridinyl)-5,6,11,11a-tetrahydro-1H-imidazo[1',5':1,6]pyrido[3,4-b]indole-1,3(2H)-dione
• 英文别名: (10R,15R)-13-butyl-10-pyridin-3-yl-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraene-12,14-dione
• 化学式: C₂₂H₂₂N₄O₂
• 分子量: 374.442
• InChiKey: VCUNYYADQMZADS-UYAOXDASSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  69.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  DL-tryptophan ethyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 、 丁酮 为溶剂， 生成 (+/-) cis-2-butyl-5-(3-pyridinyl)-5,6,11,11a-tetrahydro-1H-imidazo[1',5':1,6]pyrido[3,4-b]indole-1,3(2H)-dione
  参考文献：
  名称：

  The Discovery of Tadalafil:  A Novel and Highly Selective PDE5 Inhibitor. 1: 5,6,11,11a-Tetrahydro-1H-imidazo[1‘,5‘:1,6]pyrido[3,4-b]indole-1,3(2H)-dione Analogues

  摘要：

  Starting from ethyl beta-carboline-3-carboxylate (beta-CCE), 1, a modest inhibitor of type 5 phosphodiesterase (PDE5), a series of functionalized tetrahydro-p-carboline derivatives has been identified as a novel chemical class of potent and selective PDE5 inhibitors. Optimization of the side chain on the hydantoin ring of initial lead compound 2 and of the aromatic ring on position 5 led to the identification of compound 6e, a highly potent and selective PDE5 inhibitor, with greater selectivity for PDE5 vs PDE1-4 than sildenafil. Compound 6e demonstrated a long-lasting and significant blood pressure lowering effect after iv administration in the spontaneously hypertensive rat model but showed only moderate oral in vivo efficacy.

  DOI：

  10.1021/jm030056e

文献信息

• Microwave-assisted traceless synthesis of hydantion-fused β-carboline scaffold
  作者：Wen-Pin Yeh、Wong-Jin Chang、Mei-Lian Sun、Chung-Ming Sun

  DOI：10.1016/j.tet.2007.09.054

  日期：2007.11

  Multistep microwave-assisted reactions toward the synthesis of hydantoin-fused tricyclic tetrahydro-β-carbolines on the soluble polymer support have been developed. Polymer-bound tryptophan with various aldehydes has been subjected to Pictet–Spengler reaction to obtain tricyclic β-carboline conjugates. The terminal hydantoinyl moiety is constructed across polymer-bound β-carbolines by the reaction

  已经开发了在可溶性聚合物载体上进行多步微波辅助反应，以合成乙内酰脲的三环四氢-β-咔啉。聚合物与各种醛结合的色氨酸已进行Pictet-Spengler反应，以获得三环β-咔啉共轭物。通过在微波辐射下与各种异氰酸酯反应形成脲中间体，跨聚合物结合的β-咔啉构建末端乙内酰脲部分。尿素的同时分子内环化，然后裂解聚合物载体，导致高产率和高纯度的无痕合成四环支架。
• The Discovery of Tadalafil:  A Novel and Highly Selective PDE5 Inhibitor. 1: 5,6,11,11a-Tetrahydro-1<i>H</i>-imidazo[1‘,5‘:1,6]pyrido[3,4-<i>b</i>]indole-1,3(2<i>H</i>)-dione Analogues
  作者：Alain Daugan、Pascal Grondin、Cécile Ruault、Anne-Charlotte Le Monnier de Gouville、Hervé Coste、Jorge Kirilovsky、François Hyafil、Richard Labaudinière

  DOI：10.1021/jm030056e

  日期：2003.10.1

  Starting from ethyl beta-carboline-3-carboxylate (beta-CCE), 1, a modest inhibitor of type 5 phosphodiesterase (PDE5), a series of functionalized tetrahydro-p-carboline derivatives has been identified as a novel chemical class of potent and selective PDE5 inhibitors. Optimization of the side chain on the hydantoin ring of initial lead compound 2 and of the aromatic ring on position 5 led to the identification of compound 6e, a highly potent and selective PDE5 inhibitor, with greater selectivity for PDE5 vs PDE1-4 than sildenafil. Compound 6e demonstrated a long-lasting and significant blood pressure lowering effect after iv administration in the spontaneously hypertensive rat model but showed only moderate oral in vivo efficacy.