1,2,3,4,10,10a-Hexahydropyrazino[1,2-a]indole | 43005-54-5

• 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: 1,2,3,4,10,10a-Hexahydropyrazino[1,2-a]indole
• 英文别名: 1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole；(+/-)-1,2,3,4,10,10a-Hexahydropyrazino[1,2-a]indole
• CAS: 43005-54-5
• 化学式: C₁₁H₁₄N₂
• 分子量: 174.246
• InChiKey: IHEUMUFUCLLBOD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1,2,3,4,10,10a-Hexahydropyrazino[1,2-a]indole 在 N-甲基吗啉 、 盐酸羟胺 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 (6S,7S)-N-hydroxy-6-(3,4,10,10a-tetrahydropyrazino[1,2-a]indol-2(1H)-ylcarbonyl)-5-azaspiro[2.5]octane-7-carboxamide
  参考文献：
  名称：

  Discovery of a Potent, Selective, and Orally Active Human Epidermal Growth Factor Receptor-2 Sheddase Inhibitor for the Treatment of Cancer

  摘要：

  The design, synthesis, evaluation, and identification of a novel class of (6S,7S)-N-hydroxy-6-carboxamide-5-azaspiro[2.5]octane-7-carboxamides as the first potent and selective inhibitors of human epidermal growth factor receptor-2 (HER-2) sheddase is described. Several compounds were identified that possess excellent pharmacodynamic and pharmacokinetic properties and were shown to decrease tumor size, cleaved HER-2 extracellular domain plasma levels, and potentiate the effects of the humanized anti-HER-2 monoclonal antibody (trastuzumab) in vivo in a HER-2 overexpressing cancer murine xenograft model.

  DOI：

  10.1021/jm061344o
• 作为产物：
  描述：

  1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole hydrochloride 在 sodium hydroxide 作用下， 以 水 为溶剂， 生成 1,2,3,4,10,10a-Hexahydropyrazino[1,2-a]indole
  参考文献：
  名称：

  Novel, Versatile Three-Step Synthesis of 1,2,3,4,10,10a-Hexahydro­pyrazino[1,2-a]indoles by Intramolecular Carbene-Mediated C-H Insertion

  摘要：

  开发了一种新的便捷三步合成特权中枢神经系统骨架1,2,3,4,10,10a-六氢吡嗪并[1,2-a]吲哚的方法。该方法利用了由2-氟苯醛制得的苯基哌嗪衍生的托磺酰肼中发生的分子内碳烯介导的C-H插入。值得注意的是，哌嗪可以被其他环状氮碱替代，该方法成功扩展到了吡咯烷、哌啶、七元环胺、吗啉和同哌嗪。

  DOI：

  10.1055/s-0030-1258967

文献信息

• Synthesis and biological effects of novel 2-amino-3-(4-chlorobenzoyl)-4-substituted thiophenes as allosteric enhancers of the A1 adenosine receptor
  作者：Romeo Romagnoli、Pier Giovanni Baraldi、Maria Dora Carrion、Carlota Lopez Cara、Maria Kimatrai Salvador、Delia Preti、Mojgan Aghazadeh Tabrizi、Allan R. Moorman、Fabrizio Vincenzi、Pier Andrea Borea、Katia Varani

  DOI：10.1016/j.ejmech.2013.07.002

  日期：2013.9

  fused indole nuclei corresponding to 1,2,3,4-tetrahydropyrazino[1,2-a]indole, 1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole, tetrahydro-γ-carboline, tetrahydroisoquinoline, spiro-1,3-benzodioxolepiperidine, aliphatic tertiary amine, N-alkylaniline, aryl ether and aryl thioether templates. The 1,2,3,4-tetrahydropyrazino[1,2-a]indole derivatives 3a–c and 3e were the most active compounds in binding (saturation

  A 1腺苷受体的变构增强剂代表一种新颖且独特的药物设计策略，可以以位点和事件特定的方式增强对内源性腺苷的反应。我们先前已经研究了围绕一系列2-氨基-3-芳酰基-4-[（4-芳基哌嗪-1-基）甲基]噻吩衍生物作为A 1腺苷受体的有效变构增强剂的详细的结构-活性关系研究。。在这份手稿中，我们报告了我们对2-氨基-3-（4-氯苯甲酰基）-噻吩系统的4-位进一步取代对变构增强剂活性的影响的研究，以探索通过用芳基哌嗪部分取代芳基哌嗪部分来测定体积耐受性1,2,3,4-四氢吡嗪并[1,2- a]的一系列稠合吲哚核]吲哚，1,2,3,4,10,10a-六氢吡嗪并[1,2- a ]吲哚，四氢-γ-咔啉，四氢异喹啉，螺-1,3-苯并二氧戊哌啶，脂族叔胺，N-烷基苯胺，芳基醚和芳基硫醚模板。1,2,3,4-四氢吡嗪并[1,2- a ]吲哚衍生物3a – c和3e是结合（饱和和竞争）和功能性cAMP研究中最活跃的化合物，能够增强激动剂[
• Anti-obesity 1,2,3,4,10,10-a-hexahydropy razino [1,2-a] indoles
  申请人：——

  公开号：US20020035110A1

  公开（公告）日：2002-03-21

  The present invention is directed to 1,2,3,4,10,10a,-hexahydropyrazino[1,2-a] indole derivatives as well as pharmaceutically acceptable salts, solvates and esters thereof, wherein R 1 to R 8 have the significance given in claim 1 be used in the form of pharmaceutical preparations for the treatment or prevention of disorders of the central nervous system, damage to the central nervous system, cardiovascular disorders, gastrointestinal disorders, diabetes insipidus, obesity and sleep apnea.

  本发明涉及1,2,3,4,10,10a,-六氢吡唑[1,2-a]吲哚衍生物以及药用可接受的盐、溶剂合物和酯，其中R1至R8具有如权利要求1中所述的意义，用于以药物制剂的形式治疗或预防中枢神经系统疾病、中枢神经系统损伤、心血管疾病、胃肠疾病、尿崩症、肥胖和睡眠呼吸暂停。
• [EN] PYRAZINO[1,2-a]INDOLE COMPOUNDS, THEIR PREPARATION AND USE IN MEDICAMENTS<br/>[FR] COMPOSÉS DE PYRAZINO[1,2-A]INDOLE, LEUR PRÉPARATION ET LEUR UTILISATION DANS DES MÉDICAMENTS
  申请人：ESTEVE LABOR DR

  公开号：WO2014173903A1

  公开（公告）日：2014-10-30

  The invention refers to compounds of general formula (I) wherein the variables take the various meanings, pharmaceutical compositions containing them and their use in medicine, particularly in pain therapy.

  该发明涉及通式（I）的化合物，其中变量具有不同的含义，包括它们的制药组合物以及在医学中的使用，特别是在疼痛治疗中的应用。
• ANNELATED CARBAMOYLASE-HETEROCYCLES, FOCUSED LIBRARY, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR THE PRODUCTION THEREOF
  申请人："Chemical diversity Research Institute", Ltd.

  公开号：EP1746100A1

  公开（公告）日：2007-01-24

  This invention relates to novel annellated carbamyl-aza-heterocyclic compounds that are potential physiologically active compounds (agonists, antagonists, and receptor modulators, enzyme inhibitors, oncolytics, antibacterial and antiparasitic agents, and so on), to a focused library comprising annellated carbamyl-aza-heterocyclic compounds, a pharmaceutical composition comprising annellated carbamyl-aza-heterocyclic compounds as the active ingredient, and to methods of producing and using the same. The invention relates to annellated carbamyl-aza-heterocyclic compounds of general formula 1: wherein: W is 6-oxopiperazine, [1,4]diazepan, [1,4]thiazepan or [1,4]oxazepan compound annellated to at least one optionally substituted and optionally condensed heterocyclic compound Q; R1, R2 and R3 are, independently of one another, a hydrogen atom, an inert substituent, an optionally substituted C1-C6 alkyl, an optionally substituted C3-C8 cycloalkyl, an optionally substituted phenyl, an optionally substituted aryl, or an optionally substituted heterocyclyl; and Q is a pyrrole, pyrazole, imidazole, thiazole, pyrrolidine, indole, benzofuran, 4,5,6,7-tetrahydrobenzothiophene, thieno[3,2-b]pyrrole, furo[3,2-b]pyrrole, thieno[2,3-b]pyrrole, benzimidazole, pyridine, quinoline, or 1,2,3,4-tetrahydroisoquinoline cyclic compound.

  本发明涉及新型的环化碳酰胺-氮杂杂环化合物，这些化合物是潜在的生理活性化合物（激动剂、拮抗剂和受体调节剂、酶抑制剂、抗肿瘤剂、抗菌和抗寄生虫剂等），还涉及一种包括环化碳酰胺-氮杂杂环化合物的焦点库、一种包括环化碳酰胺-氮杂杂环化合物作为活性成分的制药组合物，以及制备和使用这些化合物的方法。本发明涉及一般式1的环化碳酰胺-氮杂杂环化合物：其中：W是6-氧代哌嗪、[1,4]二氮杂环、[1,4]硫杂环或[1,4]噁唑杂环化合物，环化到至少一个可选取代和可选缩合的杂环化合物Q；R1、R2和R3独立地是氢原子、惰性取代基、可选取代的C1-C6烷基、可选取代的C3-C8环烷基、可选取代的苯基、可选取代的芳基或可选取代的杂环基；Q是吡咯、吡唑、咪唑、噻唑、吡咯烷、吲哚、苯并呋喃、4,5,6,7-四氢苯并噻吩、噻吩[3,2-b]吡咯、呋吒[3,2-b]吡咯、噻吩[2,3-b]吡咯、苯并咪唑、吡啶、喹啉或1,2,3,4-四氢异喹啉环化合物。
• Anti-obesity 1,2,3,4,10,10a-hexahydropyrazino[1,2-a] indoles
  申请人：Bentley Mark Jonathan

  公开号：US20050239789A1

  公开（公告）日：2005-10-27

  The present invention is directed to 1,2,3,4,10,10a,-hexahydropyrazino[1,2-a]indole derivatives as well as pharmaceutically acceptable salts, solvates and esters thereof, wherein R 1 to R 8 have the significance given in claim 1 be used in the form of pharmaceutical preparations for the treatment or prevention of disorders of the central nervous system, damage to the central nervous system, cardiovascular disorders, gastrointestinal disorders, diabetes insipidus, obesity and sleep apnea.

  本发明涉及1,2,3,4,10,10a,-六氢吡嗪并[1,2-a]吲哚衍生物，以及其药学上可接受的盐、溶剂和酯，其中R1至R8在权利要求书中所给出的意义下使用，用于制备药物制剂，用于治疗或预防中枢神经系统疾病、中枢神经系统损伤、心血管疾病、胃肠道疾病、尿崩症、肥胖症和睡眠呼吸暂停。