(12aS)-2-methyl-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-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: (12aS)-2-methyl-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione
• 英文别名: (8S)-6-methyl-3,6,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),11,13,15-tetraene-4,7-dione
• 化学式: C₁₅H₁₅N₃O₂
• 分子量: 269.303
• InChiKey: CIWAQKMRYNKWFA-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  56.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  potassium (5-ethylthiophene-2-yl)trifluoroborate 、 (12aS)-2-methyl-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione 在 2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 、 水 为溶剂， 反应 4.0h， 生成 (S)-3-((2-(5-ethylthiophene-2-carbonyl)-1H-indol-3-yl)methyl)-1-methylpiperazine-2,5-dione
  参考文献：
  名称：

  Discovery of furyl/thienyl β-carboline derivatives as potent and selective PDE5 inhibitors with excellent vasorelaxant effect

  摘要：

  Based on our previous studies and predictive docking results, furans and thiophenes were introduced to the privileged tetrahydro-beta-carboline scaffold to generate more potent and selective PDE5 inhibitors. A total of 66 novel furyl/thienyl tetrahydro-beta-carboline derivatives were designed, synthesized and evaluated for PDE5 inhibition. Tetrahydro-beta-carboline-piperazinedione 19f and tetrahydro-beta-carboline-hydantoin 26b with optimized pendant 5-ethylfuran/5-ethylthiophene were identified as the most potent PDE5 inhibitors, and showed high selectivity towards PDE5 versus other PDE isozymes, especially PDE6 and PDE11. Further vasorelaxant activity assessments revealed that these PDE5 inhibitors also exhibited significant angiectasis on the norepinephrine-precontracted 3rd-order mesenteric arteries (110-150 mu m) via NO-sGC-cGMP pathway, implying their further application for the treatment of vascular diseases. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.09.028
• 作为产物：
  描述：

  (S)-2,3,4,9-四氢-1H-吡啶[3,4-b]吲哚-3-羧酸 在 磺酰氯 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 (12aS)-2-methyl-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione
  参考文献：
  名称：

  Discovery of furyl/thienyl β-carboline derivatives as potent and selective PDE5 inhibitors with excellent vasorelaxant effect

  摘要：

  Based on our previous studies and predictive docking results, furans and thiophenes were introduced to the privileged tetrahydro-beta-carboline scaffold to generate more potent and selective PDE5 inhibitors. A total of 66 novel furyl/thienyl tetrahydro-beta-carboline derivatives were designed, synthesized and evaluated for PDE5 inhibition. Tetrahydro-beta-carboline-piperazinedione 19f and tetrahydro-beta-carboline-hydantoin 26b with optimized pendant 5-ethylfuran/5-ethylthiophene were identified as the most potent PDE5 inhibitors, and showed high selectivity towards PDE5 versus other PDE isozymes, especially PDE6 and PDE11. Further vasorelaxant activity assessments revealed that these PDE5 inhibitors also exhibited significant angiectasis on the norepinephrine-precontracted 3rd-order mesenteric arteries (110-150 mu m) via NO-sGC-cGMP pathway, implying their further application for the treatment of vascular diseases. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.09.028

文献信息

• Discovery of furyl/thienyl β-carboline derivatives as potent and selective PDE5 inhibitors with excellent vasorelaxant effect
  作者：Hongbo Zheng、Yifeng Wu、Bin Sun、Chuanle Cheng、Yanan Qiao、Yuehua Jiang、Shengtian Zhao、Zhiyu Xie、Jing Tan、Hongxiang Lou

  DOI：10.1016/j.ejmech.2018.09.028

  日期：2018.10

  Based on our previous studies and predictive docking results, furans and thiophenes were introduced to the privileged tetrahydro-beta-carboline scaffold to generate more potent and selective PDE5 inhibitors. A total of 66 novel furyl/thienyl tetrahydro-beta-carboline derivatives were designed, synthesized and evaluated for PDE5 inhibition. Tetrahydro-beta-carboline-piperazinedione 19f and tetrahydro-beta-carboline-hydantoin 26b with optimized pendant 5-ethylfuran/5-ethylthiophene were identified as the most potent PDE5 inhibitors, and showed high selectivity towards PDE5 versus other PDE isozymes, especially PDE6 and PDE11. Further vasorelaxant activity assessments revealed that these PDE5 inhibitors also exhibited significant angiectasis on the norepinephrine-precontracted 3rd-order mesenteric arteries (110-150 mu m) via NO-sGC-cGMP pathway, implying their further application for the treatment of vascular diseases. (C) 2018 Elsevier Masson SAS. All rights reserved.