1-methyl-6-(trifluoromethyl)-1H-indole-2-carboxylic acid

• 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-methyl-6-(trifluoromethyl)-1H-indole-2-carboxylic acid
• 英文别名: 1-methyl-6-(trifluoromethyl)indole-2-carboxylic acid
• 化学式: C₁₁H₈F₃NO₂
• 分子量: 243.185
• InChiKey: AMEXIMIMYPKTCV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  42.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-溴-N-甲基苯胺 、 1-methyl-6-(trifluoromethyl)-1H-indole-2-carboxylic acid 在 光气 、 sodium formate 、 palladium diacetate 、 tricyclohexylphosphine tetrafluoroborate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 21.0h， 生成 1,1'-dimethyl-6'-(trifluoromethyl)-2,3'-spirobi[indolin]-2-one
  参考文献：
  名称：

  通过钯催化的脱芳香性还原-Heck反应 合成螺氧杂吲哚†

  摘要：

  开发了钯催化的C2取代的吲哚分子内脱芳香性还原-Heck反应，该反应可提供结构上不同的3,2'-螺吡咯烷氧吲哚。通过将氢化物来源更改为AcONa碱，可以得到高产率的直接C3-芳基化产物[2,3- b ]喹啉酮。还实现了C 2-取代的苯并呋喃的反应，提供了所需的螺产物。

  DOI：

  10.1039/c7ob00146k
• 作为产物：
  描述：

  6-(三氟甲基)吲哚-2-羧酸 在 sodium hydride 、 lithium hydroxide 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.67h， 生成 1-methyl-6-(trifluoromethyl)-1H-indole-2-carboxylic acid
  参考文献：
  名称：

  Discovery of 2-oxopiperazine dengue inhibitors by scaffold morphing of a phenotypic high-throughput screening hit

  摘要：

  A series of 2-oxopiperazine derivatives were designed from the pyrrolopiperazinone cell-based screening hit 4 as a dengue virus inhibitor. Systematic investigation of the structure-activity relationship (SAR) around the piperazinone ring led to the identification of compound (S)-29, which exhibited potent anti-dengue activity in the cell-based assay across all four dengue serotypes with EC50 < 0.1 mu M. Cross resistant analysis confirmed that the virus NS4B protein remained the target of the new oxopiperazine analogs obtained via scaffold morphing from the HTS hit 4. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.02.005

文献信息

• [EN] ARYL SUBSTITUTED CARBOXAMIDE DERIVATIVES AS CALCIUM OR SODIUM CHANNEL BLOCKERS<br/>[FR] DÉRIVÉS DE CARBOXAMIDE SUBSTITUÉS PAR ARYLE COMME INHIBITEURS DES CANAUX CALCIQUES OU SODIQUES
  申请人：RAQUALIA PHARMA INC

  公开号：WO2010137351A1

  公开（公告）日：2010-12-02

  The present invention relates to aryl substituted carboxamide derivatives of formula (I) or a pharmaceutically acceptable salt thereof, which have blocking activities of T-type calcium channels or voltage gated sodium channels as the tetrodotoxin-sensitive (TTX-S)blockers such as NaV1.3 and NaV1.7, and which are useful in the treatment or prevention of disorders and diseases in which T-type calcium channels or voltage gated sodium channels are involved. The invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which T-type calcium channels or voltage gated sodium channels are involved.

  本发明涉及式(I)或其药物可接受的盐的芳基取代羧酰胺衍生物，其具有T型钙通道或电压门控钠通道的阻断活性，如NaV1.3和NaV1.7等Tetrodotoxin敏感（TTX-S）阻断剂，适用于治疗或预防涉及T型钙通道或电压门控钠通道的疾病和紊乱。本发明还涉及包含这些化合物的药物组合物以及在预防或治疗涉及T型钙通道或电压门控钠通道的疾病中使用这些化合物和组合物的用途。
• ARYL SUBSTITUTED CARBOXAMIDE DERIVATIVES AS CALCIUM OR SODIUM CHANNEL BLOCKERS
  申请人：Inoue Tadashi

  公开号：US20120101105A1

  公开（公告）日：2012-04-26

  The present invention relates to aryl substituted carboxamide derivatives of formula (I) or a pharmaceutically acceptable salt thereof, which have blocking activities of T-type calcium channels or voltage gated sodium channels as the tetrodotoxin-sensitive (TTX-S) blockers such as Na v1.3 and Na v1.7 , and which are useful in the treatment or prevention of disorders and diseases in which T-type calcium channels or voltage gated sodium channels are involved. The invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which T-type calcium channels or voltage gated sodium channels are involved.

  本发明涉及公式(I)或其药学上可接受的盐的芳基取代羧酰胺衍生物，其具有T型钙通道或电压门控钠通道的阻滞活性，如Nav1.3和Nav1.7等Tetrodotoxin敏感(TTX-S)阻滞剂，并且在涉及T型钙通道或电压门控钠通道的疾病或疾病的治疗或预防中有用。本发明还涉及包含这些化合物的制药组合物以及在涉及T型钙通道或电压门控钠通道的疾病或疾病的预防或治疗中使用这些化合物和组合物的用途。
• Aryl substituted carboxamide derivatives as calcium or sodium channel blockers
  申请人：Inoue Tadashi

  公开号：US09101616B2

  公开（公告）日：2015-08-11

  The present invention relates to aryl substituted carboxamide derivatives of formula (I) or a pharmaceutically acceptable salt thereof, which have blocking activities of T-type calcium channels or voltage gated sodium channels as the tetrodotoxin-sensitive (TTX-S) blockers such as NaV1.3 and NaV1.7, and which are useful in the treatment or prevention of disorders and diseases in which T-type calcium channels or voltage gated sodium channels are involved. The invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which T-type calcium channels or voltage gated sodium channels are involved.

  本发明涉及式（I）的芳基取代羧酰胺衍生物或其药学上可接受的盐，其具有T型钙通道或电压门控钠通道的阻滞活性，如NaV1.3和NaV1.7这样的四环素敏感（TTX-S）阻滞剂，并且在治疗或预防涉及T型钙通道或电压门控钠通道的疾病和疾病方面是有用的。本发明还涉及包含这些化合物的制药组合物以及在预防或治疗涉及T型钙通道或电压门控钠通道的疾病中使用这些化合物和组合物的用途。
• [EN] MODULATORS OF THE INTEGRATED STRESS RESPONSE PATHWAY<br/>[FR] MODULATEURS DE LA VOIE DE RÉPONSE DE STRESS INTÉGRÉE
  申请人：EVOTEC INT GMBH

  公开号：WO2022084447A1

  公开（公告）日：2022-04-28

  The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts, solvates, hydrates, tautomers or stereoisomers thereof, wherein R1, R2, R3, R4a, R4b, R4c, R4d, R4f, X1, X2have the meaning as indicated in the description and claims. The invention further relates to pharmaceutical compositions comprising said compounds, their use as medicament and in a method for treating or preventing of one or more diseases or disorders associated with integrated stress response.

  本发明涉及公式（I）的化合物或其药学上可接受的盐，溶剂化合物，水合物，互变异构体或立体异构体，其中R1，R2，R3，R4a，R4b，R4c，R4d，R4f，X1，X2的含义如说明书和权利要求所示。本发明还涉及包含所述化合物的制药组合物，它们作为药物的使用以及用于治疗或预防与综合应激反应相关的一种或多种疾病或障碍的方法。
• US9101616B2
  申请人：——

  公开号：US9101616B2

  公开（公告）日：2015-08-11