(+/-) cis-ethyl 1-(3-thienyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylate

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: (+/-) cis-ethyl 1-(3-thienyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylate
• 英文别名: ethyl (1R,3R)-1-thiophen-3-yl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate
• 化学式: C₁₈H₁₈N₂O₂S
• 分子量: 326.419
• InChiKey: YOIKEZXZYFTTJV-HZPDHXFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  82.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  异氰酸正丁酯 、 (+/-) cis-ethyl 1-(3-thienyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylate 以 丁酮 为溶剂， 以22%的产率得到(+/-) cis-2-butyl-5-(3-thienyl)-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
• 作为产物：
  描述：

  3-噻吩甲醛 、 DL-tryptophan ethyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以51%的产率得到(+/-) cis-ethyl 1-(3-thienyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylate
  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

• 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.