(1R,3S)-5'-chloro-3-methyl-2,3,4,9-tetrahydrospiro[β-carboline-1,3'-indol]-2'(1'H)-one | 1193314-21-4

• 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: (1R,3S)-5'-chloro-3-methyl-2,3,4,9-tetrahydrospiro[β-carboline-1,3'-indol]-2'(1'H)-one
• 英文别名: Spiro[3H-indole-3,1'-[1H]pyrido[3,4-b]indol]-2(1H)-one,5-chloro-2',3',4',9'-tetrahydro-3'-methyl-,(1'R,3'S)-；(3R,3'S)-5-chloro-3'-methylspiro[1H-indole-3,1'-2,3,4,9-tetrahydropyrido[3,4-b]indole]-2-one
• CAS: 1193314-21-4
• 化学式: C₁₉H₁₆ClN₃O
• 分子量: 337.809
• InChiKey: QGMFKGFHTXZZHX-APBUJDDRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  56.9
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  5-氯靛红 、 (S) α-Methyltryptamine 在 对甲苯磺酸 作用下， 以 乙醇 为溶剂， 反应 16.0h， 以45%的产率得到(1R,3S)-5'-chloro-3-methyl-2,3,4,9-tetrahydrospiro[β-carboline-1,3'-indol]-2'(1'H)-one
  参考文献：
  名称：

  螺四氢 β-咔啉（螺吲哚酮）：一类新的强效口服有效化合物，用于治疗疟疾。

  摘要：

  描述了一系列螺四氢 β-咔啉的抗疟原虫活性。外消旋螺氮杂吲哚 (1) 是从野生型恶性疟原虫的表型筛选中鉴定出来的，体外 IC(50) 为 90 nM。介绍了优化 1 到化合物 20a (IC(50) = 0.2 nM) 的构效关系，包括识别活性 1R、3S 对映异构体和消除代谢负担。该系列药代动力学特征的改进在伯氏疟原虫感染的疟疾小鼠模型中转化为卓越的口服功效，在该模型中，五只小鼠中有四只每天服用 30 毫克/千克的剂量，完全治愈。

  DOI：

  10.1021/jm100410f

文献信息

• ORGANIC COMPOUNDS
  申请人：ANG Shi Hua

  公开号：US20090275560A1

  公开（公告）日：2009-11-05

  The invention relates to organic compounds which have interesting pharmaceutical properties. In particular, the compounds are useful in the treatment and/or prevention of infections such as those caused by Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale, Trypanosoma cruzi and parasites of the Leishmania genus such as, for example, Leishmania donovani . The invention also relates to pharmaceutical compositions containing the compounds, as well as processes for their preparation.

  这项发明涉及具有有趣药理特性的有机化合物。具体来说，这些化合物在治疗和/或预防由疟原虫、间日疟原虫、疟原虫、卵形疟原虫、克氏锥虫等引起的感染方面具有用途，以及像唐氏锥虫属的寄生虫，例如唐氏锥虫等。该发明还涉及含有这些化合物的药物组合物，以及它们的制备方法。
• Spiro-indole derivatives for the treatment of parasitic diseases.
  申请人：Novartis AG

  公开号：EP2722333A1

  公开（公告）日：2014-04-23

  The invention relates to organic compounds which have interesting pharmaceutical properties. In particular, the compounds are useful in the treatment and/or prevention of infections such as those caused by Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale, Trypanosoma cruzi and parasites of the Leishmania genus such as, for example, Leishmania donovani. The invention also relates to pharmaceutical compositions containing the compounds, as well as processes for their preparation.

  本发明涉及具有有趣药用特性的有机化合物。特别是，这些化合物可用于治疗和/或预防感染，如恶性疟原虫、间日疟原虫、疟疾疟原虫、卵形疟原虫、克鲁斯锥虫和利什曼属寄生虫（如唐氏利什曼原虫）引起的感染。本发明还涉及含有这些化合物的药物组合物及其制备工艺。
• Biocatalysts and methods for synthesizing derivatives of tryptamine and tryptamine analogs
  申请人：Codexis, Inc.

  公开号：US10544402B2

  公开（公告）日：2020-01-28

  The present disclosure provides engineered transaminase polypeptides for the production of amines, polynucleotides encoding the engineered transaminases, host cells capable of expressing the engineered transaminases, and methods of using the engineered transaminases to prepare compounds useful in the production of active pharmaceutical agents.

  本公开提供了用于生产胺的工程化转氨酶多肽、编码工程化转氨酶的多核苷酸、能够表达工程化转氨酶的宿主细胞，以及使用工程化转氨酶制备用于生产活性药剂的化合物的方法。
• SPIRO-INDOLE DERIVATIVES FOR THE TREATMENT OF PARASITIC DISEASES
  申请人：Novartis AG

  公开号：EP2285808B1

  公开（公告）日：2013-11-20
• BIOCATALYSTS AND METHODS FOR SYNTHESIZING DERIVATIVES OF TRYPTAMINE AND TRYPTAMINE ANALOGS
  申请人：Codexis, Inc.

  公开号：US20150072383A1

  公开（公告）日：2015-03-12

  The present disclosure provides engineered transaminase polypeptides for the production of amines, polynucleotides encoding the engineered transaminases, host cells capable of expressing the engineered transaminases, and methods of using the engineered transaminases to prepare compounds useful in the production of active pharmaceutical agents. The present disclosure provides engineered polypeptides having transaminase activity, polynucleotides encoding the polypeptides, methods of the making the polypeptides, and methods of using the polypeptides for the biocatalytic conversion of ketone substrates to amine products. The present enzymes have been engineered to have one or more residue differences as compared to the amino acid sequence of the naturally occurring transaminase of Vibrio fluvialis . In particular, the transaminases of the present disclosure have been engineered for efficient formation of chiral tryptamine derivatives from its corresponding prochiral ketone substrates.