methyl (1R,3R)-1-(benzo[d][1,3]dioxol-5-yl)-2-((S)-2-(((benzyloxy)carbonyl)amino)-5-(tert-butoxy)-5-oxopentanoyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate | 395665-88-0

• 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: methyl (1R,3R)-1-(benzo[d][1,3]dioxol-5-yl)-2-((S)-2-(((benzyloxy)carbonyl)amino)-5-(tert-butoxy)-5-oxopentanoyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate
• CAS: 395665-88-0
• 化学式: C₃₇H₃₉N₃O₉
• 分子量: 669.731
• InChiKey: JHKIQGJQCLMGHK-QSOCVKKASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.33
• 重原子数：
  49.0
• 可旋转键数：
  9.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  145.49
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  methyl (1R,3R)-1-(benzo[d][1,3]dioxol-5-yl)-2-((S)-2-(((benzyloxy)carbonyl)amino)-5-(tert-butoxy)-5-oxopentanoyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate 在 palladium 10% on activated carbon 氢气 作用下， 以 甲醇 、 溶剂黄146 为溶剂， 反应 3.0h， 以44%的产率得到(3R,6R,12aR)-6-benzo[1,3]dioxo-5-yl-3-hydroxymethyl-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：

  Fused heterocyclic derivatives as phosphodiesterase inhibitors

  摘要：

  通用结构式(I)的化合物及其盐和溶剂合物的用途，作为治疗药物。

  公开号：

  US20030207867A1
• 作为产物：
  描述：

  胡椒醛 在 吡啶 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 methyl (1R,3R)-1-(benzo[d][1,3]dioxol-5-yl)-2-((S)-2-(((benzyloxy)carbonyl)amino)-5-(tert-butoxy)-5-oxopentanoyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate
  参考文献：
  名称：

  Drug to Genome to Drug: Discovery of New Antiplasmodial Compounds

  摘要：

  The dominant strategy for discovery of new antimalarial drugs relies on cell-free assays on specific biochemical pathways of Plasmodium falciparum . However, it appears that screening directly on the parasite is a more rewarding approach. The "drug to genome to drug" approach consists of testing a small set of structural analogues of a drug acting on human proteins that have plasmodial orthologues. Both man and plasmodium possess cyclic nucleotide phosphodiesterases (PDEs) that are key players of cell homeostasis. We synthesized and tested 40 analogues of tadalafil, a human PDE5 inhibitor, on P. falciparum in culture and obtained potent inhibitors of parasite growth. We discuss the structure-activity relationships, which support the hypothesis that our compounds kill the parasite via inhibition of plasmodial PDE activity. We also prove that antiplasmodial derivatives inhibit the hydrolysis of cyclic nucleotides of the parasite, validating the cAMP/cGMP pathways as therapeutic targets against Plasmodium falciparum .

  DOI：

  10.1021/jm1014617