6-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole | 3464-80-0

• 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: 6-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole
• 英文别名: 6-Methyl-1H,2H,3H,4H,9H-pyrido[3,4-b]indole
• CAS: 3464-80-0
• 化学式: C₁₂H₁₄N₂
• mdl: MFCD07364640
• 分子量: 186.257
• InChiKey: LYHQPJGFWRVZED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  27.8
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  6-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole 在 sodium hydride 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 4.25h， 生成 tert-butyl 6,9-dimethyl-3,4-dihydro-1H-pyrido[3,4-b]indole-2-carboxylate
  参考文献：
  名称：

  Temozolomide analogs with improved brain/plasma ratios – Exploring the possibility of enhancing the therapeutic index of temozolomide

  摘要：

  Temozolomide is a chemotherapeutic agent that is used in the treatment of glioblastoma and other malignant gliomas. It acts through DNA alkylation, but treatment is limited by its systemic toxicity and neutralization of DNA alkylation by upregulation of the O-6-methylguanine-DNA methyltransferase gene. Both of these limiting factors can be addressed by achieving higher concentrations of TMZ in the brain. Our research has led to the discovery of new analogs of temozolomide with improved brain: plasma ratios when dosed in vivo in rats. These compounds are imidazotetrazine analogs, expected to act through the same mechanism as temozolomide. With reduced systemic exposure, these new agents have the potential to improve efficacy and therapeutic index in the treatment of glioblastoma. (C) 2016 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2016.08.064
• 作为产物：
  描述：

  4-甲基苯肼盐酸盐 在 盐酸 、 potassium hydroxide 、 zinc(II) chloride 作用下， 以 水 、 甲苯 为溶剂， 反应 1.0h， 生成 6-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole
  参考文献：
  名称：

  Temozolomide analogs with improved brain/plasma ratios – Exploring the possibility of enhancing the therapeutic index of temozolomide

  摘要：

  Temozolomide is a chemotherapeutic agent that is used in the treatment of glioblastoma and other malignant gliomas. It acts through DNA alkylation, but treatment is limited by its systemic toxicity and neutralization of DNA alkylation by upregulation of the O-6-methylguanine-DNA methyltransferase gene. Both of these limiting factors can be addressed by achieving higher concentrations of TMZ in the brain. Our research has led to the discovery of new analogs of temozolomide with improved brain: plasma ratios when dosed in vivo in rats. These compounds are imidazotetrazine analogs, expected to act through the same mechanism as temozolomide. With reduced systemic exposure, these new agents have the potential to improve efficacy and therapeutic index in the treatment of glioblastoma. (C) 2016 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2016.08.064

文献信息

• One-Pot Synthesis of Chromone-Fused Pyrrolo[2,1-<i>a</i>]isoquinolines and Indolizino[8,7-<i>b</i>]indoles: Iodine-Promoted Oxidative [2 + 2 + 1] Annulation of <i>O</i>-Acetylphenoxyacrylates with Tetrahydroisoquinolines and Noreleagnines
  作者：Zhi-Hao Shang、Xiang-Jin Zhang、Yi-Ming Li、Rui-Xue Wu、Hui-Ru Zhang、Lu-Ying Qin、Xue Ni、Yu Yan、An-Xin Wu、Yan-Ping Zhu

  DOI：10.1021/acs.joc.1c01682

  日期：2021.11.5

  An iodine-promoted one-pot cascade oxidative annulation reaction has been developed for the synthesis of chromone-fused-pyrrolo[2,1-a]isoquinolines and indolizino[8,7-b]indoles from o-acetylphenoxyacrylates, tetrahydroisoquinolines, and noreleagnines. This process underwent a logical approach to both chromone-fused-pyrrolo[2,1-a]isoquinolines and chromone-fused-indolizino[8,7-b]indoles isolamellarin

  已开发出碘促进的一锅级联氧化环化反应，用于从邻乙酰苯氧基丙烯酸酯、四氢异喹啉和去甲列宁合成色酮稠合吡咯并[2,1 - a ]异喹啉和吲哚并[8,7- b ]吲哚. 该过程对色酮稠合的吡咯并[2,1- a ]异喹啉和色酮稠合的吲哚嗪[8,7- b ]吲哚异层板林衍生物均采用了合乎逻辑的方法。的手法升-薄荷醇和DL -α生育酚证明这种策略的应用。
• Catalytic Enantioselective Synthesis of Spirooxindoles by Oxidative Rearrangement of Indoles
  作者：Chenxiao Qian、Pengfei Li、Jianwei Sun

  DOI：10.1002/anie.202015175

  日期：2021.3.8

  rearrangement of indoles to access oxindoles has been used as a key step in complex molecule synthesis. We report a catalytic enantioselective variant of this transformation by chiral phosphoric acid catalysis, providing rapid access to a range of enantioenriched spirooxindoles. The high enantioselectivity is controlled by dynamic kinetic resolution.

  吲哚的氧化重排以接近羟吲哚已被用作复杂分子合成中的关键步骤。我们报告了通过手性磷酸催化这种转化的催化对映选择性变体，提供了对一系列对映体富集的螺氧oo的快速访问。高对映选择性是由动态动力学拆分控制的。
• [EN] METHOD FOR TREATING 5HT2B RECEPTOR RELATED CONDITIONS<br/>[FR] METHODE DE TRAITEMENT D'ETATS ASSOCIES AU RECEPTEUR 5HT2B
  申请人：ELI LILLY AND COMPANY

  公开号：WO1995024200A1

  公开（公告）日：1995-09-14

  (EN) The present invention provides methods for binding a 5-HT2B receptor in mammals using both known and novel compounds. Further, the invention provides a method for treating or preventing 5-HT2B related conditions. Finally, the invention provides an article of manufacture.(FR) L'invention concerne des méthodes de fixation du récepteur 5-HT2B chez les mammifères au moyen de composés connus et nouveaux, ainsi qu'une méthode de traitement ou de prévention d'états associés à 5-HT2B. Un article manufacturé est également décrit.

  (EN) 本发明提供了一种使用已知和新颖化合物来结合哺乳动物中的5-HT2B受体的方法。此外，本发明还提供了一种用于治疗或预防5-HT2B相关疾病的方法。最后，本发明提供了一种制品。 (FR) La présente invention concerne des méthodes de fixation du récepteur 5-HT2B chez les mammifères au moyen de composés connus et nouveaux, ainsi qu'une méthode de traitement ou de prévention d'états associés à 5-HT2B. Un article manufacturé est également décrit.
• Indazole compound and pharmaceutical use thereof
  申请人：Takemiya Akihiro

  公开号：US20070173537A1

  公开（公告）日：2007-07-26

  The present invention can provide a cancer treatment drug containing, as an active ingredient, a substance selected from the group consisting of an indazole compound of the following formula (I), a pharmaceutically acceptable salt, a hydrate, a water adduct and a solvate:

  本发明可以提供一种癌症治疗药物，其包含以下公式（I）中的吲唑化合物、药用可接受盐、水合物、水加合物和溶剂化物等物质中所选的一种作为活性成分：
• Copper-Catalyzed Aerobic Selective Oxidation of Tetrahydrocarbolines
  作者：Jun Shi、Rui-An Wang、Wei Wu、Jun-Rong Song、Qin Chi、Wei-Dong Pan、Hai Ren

  DOI：10.1021/acs.orglett.2c01059

  日期：2022.5.13

  safe and convenient open-flask copper-catalyzed selective oxidation/functionalization methodology for tetrahydrocarbolines and tetrahydro-β-carbolines that employs atmospheric O2 as the terminal oxidant. The system is applicable to oxidative rearrangement of tetrahydro-β-carbolines, tetrahydrocarboline oxidation to α-alkoxy carbazoles and spirooxindoles, and Witkop oxidation. Mechanistic experiments indicated

  我们报告了一种使用大气 O 2作为终端氧化剂的四氢咔啉和四氢-β-咔啉的安全且方便的开瓶铜催化选择性氧化/功能化方法。该体系适用于四氢-β-咔啉的氧化重排，四氢咔啉氧化成α-烷氧基咔唑和螺氧吲哚，以及Witkop氧化。机械实验表明，单电子氧化过程负责可调选择性控制。这种铜催化协议代表了吲哚氧化领域的重大进步。