6-氰基-2-甲基吲哚 | 18871-10-8

• 物质功能分类: 医药中间体 - 杂环化合物 - 吲哚类化合物
• 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
• 中文名称: 6-氰基-2-甲基吲哚
• 中文别名: 6-甲腈-2-甲基吲哚
• 英文名称: 2-Methyl-1H-indole-6-carbonitrile
• CAS: 18871-10-8
• 化学式: C₁₀H₈N₂
• mdl: MFCD09263949
• 分子量: 156.187
• InChiKey: NYCPCICJNXATMH-UHFFFAOYSA-N

物化性质

• 熔点：
  84-85 °C
• 沸点：
  353.9±22.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  39.6
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  N-tert-butyl 4-(benzylamino)-2-chloro-7,8-dihydropyrido-[4,3-d]pyrimidine-6(5H)-carboxylate 、 6-氰基-2-甲基吲哚 在 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 1,4-二氧六环 为溶剂， 生成
  参考文献：
  名称：

  Discovery of a First-in-Class, Potent, Selective, and Orally Bioavailable Inhibitor of the p97 AAA ATPase (CB-5083)

  摘要：

  The AAA-ATPase p97 plays vital roles in mechanisms of protein homeostasis, including ubiquitin proteasome system (ups) mediated protein degradation, endoplasmic reticulum-associated degradation (BRAD), and autophagy. Herein we describe our lead optimization efforts focused on in vitro potency, ADME, and pharmaceutical properties that led to the discovery of a potent, ATP-competitive, D2-selective, and orally bioavailable p97 inhibitor 71, CB-6083. Treatment of tumor cells with 71 leads to significant accumulation of markers associated with inhibition of UPS and ERAD functions, which induces irresolvable proteotoxic stress and cell, death. In tumor bearing mice, oral administration of 71 causes rapid accumulation Of markers of the unfolded protein response (UPR) and subsequently induces apoptosis leading to Sustained antitumor activity in in vivo, xenograft models of both solid and hematological tumors. 71 has been taken into phase I clinical trials in patients with multiple myeloma and solid tumors.

  DOI：

  10.1021/acs.jmedchem.5b01346
• 作为产物：
  描述：

  6-氰基吲哚 在 正丁基锂 、 sodium hydride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 生成 6-氰基-2-甲基吲哚
  参考文献：
  名称：

  Discovery of a First-in-Class, Potent, Selective, and Orally Bioavailable Inhibitor of the p97 AAA ATPase (CB-5083)

  摘要：

  The AAA-ATPase p97 plays vital roles in mechanisms of protein homeostasis, including ubiquitin proteasome system (ups) mediated protein degradation, endoplasmic reticulum-associated degradation (BRAD), and autophagy. Herein we describe our lead optimization efforts focused on in vitro potency, ADME, and pharmaceutical properties that led to the discovery of a potent, ATP-competitive, D2-selective, and orally bioavailable p97 inhibitor 71, CB-6083. Treatment of tumor cells with 71 leads to significant accumulation of markers associated with inhibition of UPS and ERAD functions, which induces irresolvable proteotoxic stress and cell, death. In tumor bearing mice, oral administration of 71 causes rapid accumulation Of markers of the unfolded protein response (UPR) and subsequently induces apoptosis leading to Sustained antitumor activity in in vivo, xenograft models of both solid and hematological tumors. 71 has been taken into phase I clinical trials in patients with multiple myeloma and solid tumors.

  DOI：

  10.1021/acs.jmedchem.5b01346

文献信息

• [EN] CXCR4 RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DU RÉCEPTEUR CXCR4
  申请人：PROXIMAGEN LTD

  公开号：WO2012049277A1

  公开（公告）日：2012-04-19

  The compounds of formula (I) are antagonists of the CXCR4 receptor Wherein R1 , X, Y and R2 are as defined in the claims.

  式(I)的化合物是CXCR4受体的拮抗剂，其中R1、X、Y和R2如权利要求中所定义。
• METHOD FOR PREPARING ALECTINIB
  申请人：SUZHOU MIRACPHARMA TECHNOLPGY CO., LTD.

  公开号：US20170247352A1

  公开（公告）日：2017-08-31

  A method for preparing Alectinib (Alectinib, I), comprising the preparation steps: subjecting 6-cyano-1H-indole-3-carboxylate and 4-ethyl-3-(4-morpholine-4-yl-piperidine-1-yl)-α,α-dimethylbenzyl alcohol to condensation, hydrolyzing and cyclization reaction so as to prepare Alectinib (I). The preparation method has easily available raw materials and a simple process, and is economical and environmentally friendly and suitable for industrial production.

  一种制备阿雷替尼（Alectinib, I）的方法，包括以下制备步骤：将6-氰基-1H-吲哚-3-甲酸酯和4-乙基-3-(4-吗啡啉-4-基哌啶-1-基)-α,α-二甲基苄醇进行缩合、水解和环化反应，以制备阿雷替尼（I）。该制备方法具有原料易得、工艺简单、经济环保且适合工业生产的特点。
• [EN] 6-SUBSTITUTED 2,3,4,5-TETRAHYDRO-1H-BENZO[D]AZEPINES AS 5-HT2C RECEPTOR AGONISTS<br/>[FR] 2,3,4,5-TETRAHYDRO-1H-BENZO[D]AZEPINES SUBSTITUES EN POSITION 6 EN TANT QU'AGONISTES DE RECEPTEUR 5-HT2C
  申请人：LILLY CO ELI

  公开号：WO2005082859A1

  公开（公告）日：2005-09-09

  The present invention provides 6-substituted 2,3,4,5-tetrahydro-1H-benzo[d]azepines of Formula I as selective 5-HT2C receptor agonists for the treatment of 5-HT2C associated disorders including obesity, obsessive/compulsive disorder, depression, and anxiety: I where: R6 is -C=C-R10, -O-R12, -S-R14, or -NR24R25; and other substituents are as defined in the specification.

  本发明提供了公式I中的6-取代的2,3,4,5-四氢-1H-苯并[d]氮杂环庚烯作为选择性5-HT2C受体激动剂，用于治疗与5-HT2C相关的疾病，包括肥胖症、强迫症/强迫性障碍、抑郁症和焦虑症：I其中：R6为-C=C-R10，-O-R12，-S-R14或-NR24R25；其他取代基如规范中所定义。
• [EN] INDOLE DERIVATIVES USEFUL AS ENDOTHELIN RECEPTOR ANTAGONISTS<br/>[FR] DERIVES D'INDOLE UTILES EN TANT QU'ANTAGONISTES DU RECEPTEUR DE L'ENDOTHELINE
  申请人：PFIZER INC.

  公开号：WO1997043260A1

  公开（公告）日：1997-11-20

  (EN) Compounds of formula (I), and their pharmaceutically acceptable derivatives, wherein R1 and R2 are optional substituents and independently represent C1-6 alkyl, C2-6 alkenyl [optionally substituted by CO2H or CO2(C1-6 alkyl)], C2-6 alkynyl, halogen, C1-3 perfluoroalkyl, (CH2)mAr1, (CH2)mHet1, (CH2)mCONR7R8, (CH2)mCO2R8, O(CH2)qCO2R8, (CH2)mCOR8, (CH2)mOR8, O(CH2)pOR8, (CH2)mNR7R8, CO2(CH2)qNR7R8, (CH2)mCN, S(O)nR8, SO2NR7R8, CONH(CH2)mAr1 or CONH(CH2)mHet1; R3 represents H, C1-6 alkyl, (CH2)pNR9R10, SO2R10, SO2NR9R10, (CH2)mCOR10, C2-6 alkenyl, C2-6 alkynyl, (CH2)mCONR9R10, (CH2)mCO2R10, (CH2)pCN, (CH2)pR10 or (CH2)pOR10; R4 represents H or C1-6 alkyl; R5 represents H or OH; R6 represents phenyl optionally fused to a heterocyclic ring, the group as a whole being optionally substituted; R7-10 are fully defined herein and may independently represent Ar2 or Het2; Z represents CO2H, CONH(tetrazol-5-yl), CONHSO2O(C1-4 alkyl), CO2Ar3, CO2(C1-6 alkyl), tetrazol-5-yl, CONHSO2Ar3, CONHSO2(CH2)qAr3 or CONHSO2(C1-6 alkyl); Ar1-3 independently represent phenyl, naphthyl, or an aromatic heterocycle, which groups are optionally fused and optionally substituted; and Het1 and Het2 independently represent a non-aromatic heterocycle which is optionally substituted; are useful in the treatment of restenosis, renal failure and pulmonary hypertension.(FR) Composés de formule (I) et leurs dérivés acceptables sur le plan pharmaceutique. Dans ladite formule, R1 et R2 sont des substituants optionnels et représentent indépendamment alkyle C1-6, alcényle C2-6 [éventuellement substitué par CO2H ou CO2(alkyle C1-6)], alcynyle C2-6, halogène, perfluoroalkyle C1-3, (CH2)mAR1, (CH2)mHet1, (CH2)mCONR7R8, (CH2)mCO2R8, O(CH2)qCO2R8, (CH2)mCOR8, (CH2)mOR8, O(CH2)pOR8, (CH2)mNR7R8, CO2(CH2)qNR7R8, (CH2)mCN, S(O)nR8,SO2NR7R8, CONH(CH2)mAr1 ou CONH(CH2)mHet1; R3 représente H, alkyle C1-6, (CH2)pNR9R10, SO2R10, SO2NR9R10, (CH2)mCOR10, alcényle C2-6, alcynyle C2-6, (CH2)mCONR9R10, (CH2)mCO2R10, (CH2)pCN, (CH2)pR10 ou (CH2)pOR10; R4 représente H ou alkyle C1-6; R5 représente H ou OH; R6 représente phényle éventuellement fusionné à un noyau hétérocyclique, le groupe dans son intégralité étant éventuellement substitué; R7-10 sont intégralement définis dans la description et peuvent représenter indépendamment Ar2 ou Het2; Z représente CO2H, CONH(tétrazol-5-yle), CONHSO2O(alkyle C1-4), CO2Ar3, CO2(alkyle C1-6), tétrazol-5-yle, CONHSO2Ar3, CONHSO2(CH2)qAr3 ou CONHSO2(alkyle C1-6); Ar1-3 représente indépendamment phényle, naphtyle ou un hérétocycle non aromatique dont les groupes sont éventuellement fusionnés et substitués; et Het1 et Het2 représentent indépendamment un hétérocycle aromatique éventuellement substitué. Les composés selon l'invention sont utiles dans le traitement de la resténose, de l'insuffisance rénale et de l'hypertension pulmonaire.

  化合物公式（I）及其药学上可接受的衍生物，其中R1和R2为可选取代基团，独立地表示C1-6烷基，C2-6烯基[可选取代为CO2H或CO2（C1-6烷基）]，C2-6炔基，卤素，C1-3全氟烷基，（CH2）mAr1，（CH2）mHet1，（CH2）mCONR7R8，（CH2）mCO2R8，O（CH2）qCO2R8，（CH2）mCOR8，（CH2）mOR8，O（CH2）pOR8，（CH2）mNR7R8，CO2（CH2）qNR7R8，（CH2）mCN，S（O）nR8，SO2NR7R8，CONH（CH2）mAr1或CONH（CH2）mHet1；R3表示H，C1-6烷基，（CH2）pNR9R10，SO2R10，SO2NR9R10，（CH2）mCOR10，C2-6烯基，C2-6炔基，（CH2）mCONR9R10，（CH2）mCO2R10，（CH2）pCN，（CH2）pR10或（CH2）pOR10；R4表示H或C1-6烷基；R5表示H或OH；R6表示苯基，可选地融合到杂环环上，整个基团可选地取代；R7-10在此完全定义，可以独立地表示Ar2或Het2；Z表示CO2H，CONH（四唑-5-基），CONHSO2O（C1-4烷基），CO2Ar3，CO2（C1-6烷基），四唑-5-基，CONHSO2Ar3，CONHSO2（CH2）qAr3或CONHSO2（C1-6烷基）；Ar1-3独立地表示苯基，萘基或芳香杂环，这些基团可选地融合和可选地取代；Het1和Het2独立地表示非芳香杂环，可选地取代；在治疗再狭窄、肾衰竭和肺动脉高压方面具有用处。
• RHO KINASE INHIBITORS
  申请人：Cook Brian Nicholas

  公开号：US20120165322A1

  公开（公告）日：2012-06-28

  The present invention relates to compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein R 1 and R 2 are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

  本发明涉及式(I)的化合物和其药学上可接受的盐，其中R1和R2的定义如本文所述。本发明还涉及包含这些化合物的药物组合物、使用这些化合物治疗各种疾病和障碍的方法、制备这些化合物的过程以及在这些过程中有用的中间体。