2-methyl-8-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole | 17223-49-3

• 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: 2-methyl-8-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole
• 英文别名: 8-Trifluormethyl-2-methyl-2,3,4,5-tetrahydro-1H-pyrido<4,3-b>indol；2-methyl-8-(trifluoromethyl)-1,3,4,5-tetrahydropyrido[4,3-b]indole
• CAS: 17223-49-3
• 化学式: C₁₃H₁₃F₃N₂
• 分子量: 254.255
• InChiKey: QAAGPGRGDSPHQO-UHFFFAOYSA-N

物化性质

• 熔点：
  168-170 °C
• 沸点：
  334.1±37.0 °C(Predicted)
• 密度：
  1.315±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  19
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-methyl-8-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 、 1-(3-溴丙氧基)-4-氯苯 在 potassium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 反应 0.25h， 以63.9%的产率得到5-(3-(4-chlorophenoxy)propyl)-2-methyl-8-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole
  参考文献：
  名称：

  Novel Carboline Derivatives as Potent Antifungal Lead Compounds: Design, Synthesis, and Biological Evaluation

  摘要：

  A series of novel antifungal carboline derivatives was designed and synthesized, which showed broad-spectrum antifungal activity. Particularly, compound C38 showed comparable in vitro antifungal activity to fluconazole without toxicity to human embryonic lung cells. It also exhibited good fungicidal activity against both fluconazole-sensitive and -resistant Candida albicans cells and had potent inhibition activity against Candida albicans biofilm formation and hyphal growth. Moreover, C38 showed good synergistic antifungal activity in combination with fluconazole (FLC) against FLC-resistant Candida species. Preliminary mechanism studies revealed that C38 might act by inhibiting the synthesis of fungal cell wall.

  DOI：

  10.1021/ml400492t
• 作为产物：
  描述：

  3-(2-azido-5-trifluoromethylphenyl)pyridine 在 sodium tetrahydroborate 、 水合三氯化钌 作用下， 以 甲醇 、 二氯甲烷 、 醋酸异丙酯 、 水 为溶剂， 反应 15.0h， 生成 2-methyl-8-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole
  参考文献：
  名称：

  钌催化芳基叠氮化物形成 γ-碳鎓离子；二甲酚的合成

  摘要：

  通过 3-吡啶基取代的芳基叠氮化物的钌 (III) 催化反应，立体选择性地生产一系列 γ-咔啉。其他催化剂和条件既没有那么选择性，也没有那么高产率。该方法用于简洁、高效地合成二甲苯啉。

  DOI：

  10.1021/ol2008268

文献信息

• [EN] PYRIDO (4,3-B) INDOLES CONTAINING RIGID MOIETIES<br/>[FR] PYRIDO[4,3-B]INDOLES CONTENANT DES FRAGMENTS RIGIDES
  申请人：MEDIVATION TECHNOLOGIES INC

  公开号：WO2010051501A1

  公开（公告）日：2010-05-06

  This disclosure is directed to pyrido[4,3-b]indoles having rigid moieties. The compounds in one embodiment are pyrido[4,3-b]indoles having an unsaturated hydrocarbon moiety. The compounds in another embodiment are pyrido[4,3-b]indoles having a cycloalkyl, cycloalkenyl or heterocyclyl moiety. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder.

  本公开涉及具有刚性基团的吡啶并[4,3-b]吲哚化合物。在一个实施例中，这些化合物是具有不饱和碳氢基团的吡啶并[4,3-b]吲哚化合物。在另一个实施例中，这些化合物是具有环烷基、环烯基或杂环基团的吡啶并[4,3-b]吲哚化合物。还提供了包括这些化合物的药物组合物，以及使用这些化合物在各种治疗应用中的方法，包括治疗认知障碍、精神障碍、神经递质介导的障碍和/或神经元障碍。
• COMPOUNDS AND METHODS FOR TREATMENT OF HYPERTENSION
  申请人：Medivation Technologies, Inc.

  公开号：US20150266884A1

  公开（公告）日：2015-09-24

  Hydrogenated pyrido[4,3-b]indoles, pyrido[3,4-b]indoles and azepino[4,5-b]indoles are described. The compounds may bind to and are adrenergic receptor α 2B antagonists. The compounds may also bind to and antagonize adrenergic receptor α 1B . The compounds may find use in therapy, e.g., to (i) reduce blood pressure and/or (ii) promote renal blood flow and/or (iii) decrease or inhibit sodium reabsorption. The compounds may also be used to treat diseases or conditions that are, or are expected to be, responsive to a decrease in blood pressure. Use of the compounds to treat cardiovascular and renal disorders is particularly described.

  氢化吡啶并[4,3-b]吲哚，吡啶[3,4-b]吲哚和氮杂七元[4,5-b]吲哚被描述。这些化合物可能与肾上腺素受体α2B结合并拮抗。这些化合物也可能与肾上腺素受体α1B结合并拮抗。这些化合物可能在治疗中发挥作用，例如（i）降低血压和/或（ii）促进肾脏血流和/或（iii）减少或抑制钠重吸收。这些化合物也可用于治疗对降低血压有反应或预期会有反应的疾病或症状。特别描述了使用这些化合物治疗心血管和肾脏疾病。
• 1,2,3,4-Tetrahydro-γ-carbolinium salts: novel reactions with thiols, mediated by polymer-supported reagents
  作者：Mike E. Lizarzaburu、Stephen J. Shuttleworth

  DOI：10.1016/j.tetlet.2004.04.078

  日期：2004.6

  A series of dialkyl-[2-(3-alkylsulfanylmethyl-1H-indol-2-yl)-ethyl]amines was produced using a novel route involving nucleophilic ring opening of 2,2-dialkyl-1,2,3,4-tetrahydro-γ-carbolinium salts with thiols. The insertion reaction was mediated by a strong, polymer-supported base, and the purification of the target compounds was facilitated using resin-bound sulfonic acid.

  使用涉及2,2-二烷基-1,2,3,4的亲核开环的新途径制备了一系列二烷基-[2-（3-烷基硫烷基甲基-1 H-吲哚-2-基）-乙基]胺-四氢-γ-碳鎓盐与硫醇。插入反应由牢固的聚合物支撑的碱介导，并且使用树脂结合的磺酸促进目标化合物的纯化。
• Synthesis and biological evaluation of novel γ-carboline analogues of Dimebon as potent 5-HT6 receptor antagonists
  作者：Alexandre V. Ivachtchenko、Eugene B. Frolov、Oleg D. Mitkin、Volodymyr M. Kysil、Alexander V. Khvat、Ilya M. Okun、Sergey E. Tkachenko

  DOI：10.1016/j.bmcl.2009.04.128

  日期：2009.6

  Synthesis, biological evaluation and structure–activity relationships for a series of novel γ-carboline analogues of Dimebon™ are described. Among the studied compounds, γ-carbolines 38} and 314} have been identified as potent small molecule antagonists of histamine H1 (IC50 = 0.1 μM) and serotonin 5-HT6 (IC50 = 0.37 μM) receptors, respectively.

  描述了一系列新的Dimebon ™ γ-咔啉类似物的合成，生物学评估和结构-活性关系。在研究的化合物中，已确定γ-咔啉3 8}和3 14 }是组胺H 1（IC 50  = 0.1μM）和5-羟色胺5-HT 6（IC 50  = 0.37μM）受体的有效小分子拮抗剂。， 分别。
• [EN] METHODS AND COMPOSITIONS FOR TREATING PSYCHOTIC DISORDERS USING ANTIPSYCHOTIC COMBINATION THERAPY<br/>[FR] PROCÉDÉS ET COMPOSITIONS POUR TRAITER DES TROUBLES PSYCHOTIQUES UTILISANT UNE THÉRAPIE D'ASSOCIATION ANTIPSYCHOTIQUE
  申请人：MEDIVATION TECHNOLOGIES INC

  公开号：WO2011103448A1

  公开（公告）日：2011-08-25

  The present invention provides methods, compositions, and kits for use in combination therapy for treating, preventing, delaying the onset and/or delaying the development of (i) a psychotic disorder in an individual in need thereof, (ii) a psychotic disorder in an individual who is also in need of improved cognition, or (iii) a disorder characterized by causing at least one psychotic symptom and at least one cognitive symptom in an individual in need thereof, comprising compound I and a second agent (e.g., an antipsychotic) or pharmaceutically acceptable salt of any of the foregoing.

  本发明提供了用于联合治疗的方法、组合物和试剂盒，用于治疗、预防、延缓发病和/或延缓发展 (i) 需要治疗的个体中的精神疾患，(ii) 需要改善认知的个体中的精神疾患，或 (iii) 需要治疗的个体中表现为至少一种精神症状和至少一种认知症状的疾病，包括化合物 I 和第二药剂（例如，抗精神病药物）或上述任何药物的药学上可接受的盐。