4-bromo-1-(phenylsulfonyl)-1H-indole | 412048-77-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-bromo-1-(phenylsulfonyl)-1H-indole
• 英文别名: 1-(benzenesulfonyl)-4-bromo-1H-indole；1-(benzenesulfonyl)-4-bromoindole
• CAS: 412048-77-2
• 化学式: C₁₄H₁₀BrNO₂S
• 分子量: 336.209
• InChiKey: HCVHHKPCZJWQCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  47.4
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P305+P351+P338,P330,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  存储条件：密封、干燥、避光、在惰性气体中保存，适宜温度为2-8°C。

反应信息

• 作为反应物：
  描述：

  4-bromo-1-(phenylsulfonyl)-1H-indole 在 氯化亚砜 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正庚烷 为溶剂， 反应 3.0h， 生成 1-benzenesulfonyl-4-bromo-1H-indole-2-carbonyl chloride
  参考文献：
  名称：

  Novel Bis(1H-indol-2-yl)methanones as Potent Inhibitors of FLT3 and Platelet-Derived Growth Factor Receptor Tyrosine Kinase

  摘要：

  FLT3 receptor tyrosine kinase is aberrantly active in many cases of acute myeloid leukemia (AML). Recently, bis(1H-indol-2-yl) methanones were found to inhibit FLT3 and PDGFR kinases. To optimize FLT3 activity and selectivity, 35 novel derivatives were synthesized and tested for inhibition of FLT3 and PDGFR autophosphorylation. The most potent FLT3 inhibitors 98 and 102 show IC50 values of 0.06 and 0.04 mu M, respectively, and 1 order of magnitude lower PDGFR inhibiting activity. The derivatives 76 and 82 are 20- to 40- fold PDGFR selective. Docking at the recent FLT3 structure suggests a bidentate binding mode with the backbone of Cys-694. Activity and selectivity can be related to interactions of one indole moiety with a hydrophobic pocket including Phe-691, the only different binding site residue (PDGFR Thr-681). Compound 102 inhibited the proliferation of 32D cells expressing wildtype FLT3 or FLT3-ITD similarly as FLT3 autophosphorylation, and induced apoptosis in primary AML patient blasts.

  DOI：

  10.1021/jm058033i
• 作为产物：
  描述：

  苯磺酰氯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 生成 4-bromo-1-(phenylsulfonyl)-1H-indole
  参考文献：
  名称：

  WO2007/61694

  摘要：

  公开号：

文献信息

• Structural Modification of the 3,4,5-Trimethoxyphenyl Moiety in the Tubulin Inhibitor VERU-111 Leads to Improved Antiproliferative Activities
  作者：Qinghui Wang、Kinsie E. Arnst、Yuxi Wang、Gyanendra Kumar、Dejian Ma、Hao Chen、Zhongzhi Wu、Jinliang Yang、Stephen W. White、Duane D. Miller、Wei Li

  DOI：10.1021/acs.jmedchem.8b00827

  日期：2018.9.13

  Colchicine binding site inhibitors (CBSIs) hold great potential in developing new generations of antimitotic drugs. Unlike existing tubulin inhibitors such as paclitaxel, they are generally much less susceptible to resistance caused by the overexpression of drug efflux pumps. The 3,4,5-trimethoxyphenyl (TMP) moiety is a critical component present in many CBSIs, playing an important role in maintaining

  秋水仙碱结合位点抑制剂（CBSI）在开发新一代抗有丝分裂药物方面具有巨大潜力。与现有的微管蛋白抑制剂（例如紫杉醇）不同，它们通常不易受到药物外排泵过表达引起的耐药性的影响。3,4,5-三甲氧基苯基（TMP）部分是许多CBSI中存在的关键组分，在维持CBSI的合适分子构象并促进其与微管蛋白的高结合亲和力中起重要作用。先前报道的各种CBSI支架中TMP部分的修饰通常导致抗增殖能力降低。我们之前曾报道过一种有效的CBSI，即VERU-111，它也含有TMP部分。在此，我们报告发现VERU-111类似物13f比VERU-111更有力。与微管蛋白复合的13f的X射线晶体结构证实了其与秋水仙碱位点的直接结合。另外，13f在体内对肿瘤生长表现出强烈的抑制作用。
• Novel compounds, their use and preparation
  申请人：——

  公开号：US20020165251A1

  公开（公告）日：2002-11-07

  The invention provides 2, 3-, 4- or 5-substituted-N1-(arylsulfonyl)indole and (heteroaryl)indole compounds of the general formula (I): 1 in which Ar, R 2 , R 3 , R 4 and R 5 are as defined in the specification. The compounds bind to the 5-HT 6 receptor and are useful for the treatment and prophylaxis of disorders mediated by the 5-HT 6 receptor, such as obesity and CNS disorders.

  这项发明提供了一般式(I)中的2,3-,4-或5-取代-N1-(芳基磺酰基)吲哚和(杂环基)吲哚化合物： 其中Ar，R2，R3，R4和R5如规范中定义。这些化合物与5-HT6受体结合，并可用于治疗和预防由5-HT6受体介导的疾病，如肥胖和中枢神经系统疾病。
• ETHYNYLINDOLE COMPOUNDS
  申请人：OHMOTO Kazuyuki

  公开号：US20100160647A1

  公开（公告）日：2010-06-24

  As a compound having a potent oral activity and a long-lasting cysLT 1 /cysLT 2 receptor antagonistic activity, the compound of the formula (I): which exhibits potent antagonistic activity against the cysLT 1 /cysLT 2 receptor, and have long-lasting effects even in case of oral administration, and therefore is useful as an oral agent for preventing and/or treating a variety of diseases, for example, respiratory disease (for example, asthma (bronchial asthma, etc.), chronic obstructive pulmonary disease (COPD), pulmonary emphysema, chronic bronchitis, pneumonia (interstitial pneumonia, etc.), severe acute respiratory syndrome (SARS), acute respiratory distress syndrome (ARDS), apnea syndrome, allergic rhinitis, sinusitis (acute sinusitis, chronic sinusitis, etc.), pulmonary fibrosis, coughing (chronic coughing, etc.), and the like) was developed.

  作为一种具有强效口服活性和长效cysLT1/cysLT2受体拮抗活性的化合物，具有公式(I)的化合物表现出对cysLT1/cysLT2受体的强效拮抗活性，并且即使口服后也具有长效作用，因此可用作口服药剂预防和/或治疗各种疾病，例如呼吸道疾病（例如哮喘（支气管哮喘等）、慢性阻塞性肺病（COPD）、肺气肿、慢性支气管炎、肺炎（间质性肺炎等）、严重急性呼吸综合征（SARS）、急性呼吸窘迫综合征（ARDS）、呼吸暂停综合征、过敏性鼻炎、鼻窦炎（急性鼻窦炎、慢性鼻窦炎等）、肺纤维化、咳嗽（慢性咳嗽等）等）。
• [EN] INHIBITORS OF BRUTON'S TYROSINE KINASE<br/>[FR] INHIBITEURS DE LA TYROSINE KINASE DE BRUTON
  申请人：HOFFMANN LA ROCHE

  公开号：WO2015086635A1

  公开（公告）日：2015-06-18

  This application discloses compounds according to generic Formula (I): wherein all variables are defined as described herein, which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are useful for the treatment of oncological, auto-immune, and inflammatory diseases caused by aberrant B-cell activation. Also disclosed are compositions containing compounds of Formula (I) and at least one carrier, diluent or excipient.

  本申请揭示了根据通用式（I）定义的化合物，其中所有变量如本文所述，这些化合物抑制Btk。本文披露的化合物可用于调节Btk的活性并治疗与过度Btk活性相关的疾病。这些化合物可用于治疗由异常B细胞激活引起的肿瘤学、自身免疫和炎症性疾病。还披露了包含通用式（I）化合物和至少一种载体、稀释剂或赋形剂的组合物。
• [EN] FUSED PYRIMIDINES AS INHIBITORS OF p97 COMPLEX<br/>[FR] PYRIMIDINES FUSIONNÉES EN TANT QU'INHIBITEURS DU COMPLEXE P97
  申请人：ZHOU HAN-JIE

  公开号：WO2014015291A1

  公开（公告）日：2014-01-23

  Fused pyrimidine compounds having a saturated, unsaturated or aromatic A ring fused to a pyrimidine ring and having a complex substituents at the 2 position and a substituted amine at the 4 position of the pyrimidine ring as well as optional aliphatic, functional and/or aromatic components substituted at other positions of the pyrimidine ring and A ring are disclosed. These compounds are inhibitors of the AAA proteasome complex containing p97 and are effective medicinal agents for treatment of diseases associated with p97 bioactivity such as cancer.

  本发明揭示了一种融合嘧啶化合物，其具有饱和、不饱和或芳香性A环与嘧啶环融合，并在嘧啶环的2位具有复杂的取代基，在4位具有取代胺基，以及在其他位置可选地具有取代的脂肪族、功能性和/或芳香性组分的嘧啶环和A环。这些化合物是包含p97的AAA蛋白酶复合物的抑制剂，是治疗与p97生物活性相关的疾病如癌症的有效药物。