4-chloro-1-phenylsulfonyl-1H-indole | 896137-68-1

• 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-chloro-1-phenylsulfonyl-1H-indole
• 英文别名: 1-(Benzenesulfonyl)-4-chloroindole
• CAS: 896137-68-1
• 化学式: C₁₄H₁₀ClNO₂S
• 分子量: 291.758
• InChiKey: FPWIBJOGIQYKCJ-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

反应信息

• 作为反应物：
  描述：

  4-chloro-1-phenylsulfonyl-1H-indole 在 正丁基锂 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.0h， 生成 (4-Chloro-1H-indol-2-yl)-(5-methoxy-1H-indol-2-yl)-methanone
  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：

  4-氯吲哚 、 苯磺酰氯 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以92%的产率得到4-chloro-1-phenylsulfonyl-1H-indole
  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

文献信息

• [EN] 5-AZAINDOLE COMPOUNDS WITH ANTICANCER AND ANTIANGIOGENIC ACTIVITIES<br/>[FR] COMPOSÉS 5-AZAINDOLE AYANT DES ACTIVITÉS ANTI-CANCER ET ANTI-ANGIOGÉNIQUE
  申请人：CENTRE NAT RECH SCIENT

  公开号：WO2014033597A1

  公开（公告）日：2014-03-06

  The present invention relates to 5-azaindole type compounds responding to the following formula (I): for their use as drugs, and more particularly for the prevention and/or the treatment of diseases and/or disorders chosen amongst cancers; angiogenesis related disorders; parasitic diseases; fungal diseases; autoimmune diseases; inflammatory diseases; warts such as warts caused by papilloma virus. The invention also relates to pharmaceutical compositions comprising such compounds of formula (I). The use of at least one compound of formula (I) as research tool for the cell-cycle synchronization of microtubule drugs resistant cell lines is also part of the invention. Finally, the invention also concerns the use of at least one compound of formula (I) as an herbicide and/or an algaecide.

  本发明涉及响应以下式（I）的5-氮杂吲哚类化合物的用途，用于药物，更具体地用于预防和/或治疗癌症等疾病和/或疾病，包括癌症；与血管生成相关的疾病；寄生虫病；真菌病；自身免疫性疾病；炎症性疾病；乳头状瘤病毒引起的疣等。该发明还涉及包含该式（I）化合物的药物组合物。至少一种式（I）化合物作为微管药物耐药细胞系细胞周期同步的研究工具的用途也是本发明的一部分。最后，该发明还涉及至少一种式（I）化合物作为除草剂和/或杀藻剂的用途。
• General asymmetric synthesis of 2,2,2-trifluoro-1-(1H-indol-3- and -2-yl)ethanamines
  作者：Lingmin Wu、Chen Xie、Jie Zhou、Haibo Mei、Vadim A. Soloshonok、Jianlin Han、Yi Pan

  DOI：10.1016/j.jfluchem.2015.01.001

  日期：2015.2

  functionalization of the pyrrole ring of an indole structure with (2,2,2-trifluoro)ethylamine moiety allowing for general access to two novel classes of trifluoromethyl-containing indoles. We found that under the Friedel–Crafts reaction conditions (S)-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimine (1) easily reacts with indole derivatives affording the target 3-substituted products, while LDA-promoted reactions

  这项工作描述了吲哚结构的吡咯环具有（2,2,2-三氟）乙胺部分的不对称官能化，该官能团使得能够普遍获得两类新的含三氟甲基的吲哚。我们发现，Friedel-Crafts反应条件下（小号） - ñ -叔丁基亚-3,3,3- trifluoroacetaldimine（1）发生反应容易用的吲哚衍生物，得到目标的3-取代的产品，而LDA促进的反应进行排他性在2位。我们证明这两种方法都具有广泛的底物范围，高化学收率和非对映选择性，这使得这些反应易于用于直接制备含有手性CF的生物学上感兴趣的化合物3 CH（NH 2）和吲哚基。提出了解释立体化学偏爱模式的机械原理。
• Discovery of a First-in-Class, Potent, Selective, and Orally Bioavailable Inhibitor of the p97 AAA ATPase (CB-5083)
  作者：Han-Jie Zhou、Jinhai Wang、Bing Yao、Steve Wong、Stevan Djakovic、Brajesh Kumar、Julie Rice、Eduardo Valle、Ferdie Soriano、Mary-Kamala Menon、Antonett Madriaga、Szerenke Kiss von Soly、Abhinav Kumar、Francesco Parlati、F. Michael Yakes、Laura Shawver、Ronan Le Moigne、Daniel J. Anderson、Mark Rolfe、David Wustrow

  DOI：10.1021/acs.jmedchem.5b01346

  日期：2015.12.24

  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.
• [EN] INDOLE SULFONAMIDES AS SFRP-1 MODULATORS<br/>[FR] SULFAMIDES D'INDOLE MODULATEURS DE SFRP-1
  申请人：WYETH CORP

  公开号：WO2008060998A1

  公开（公告）日：2008-05-22

  [EN] Indole sulfonamide compounds or pharmaceutically acceptable salts thereof, are provided, which are modulators of secreted frizzled related protein-1. The compounds, and compositions containing the compounds, can be used to treat a variety of disorders, including osteoporosis. (I) R¹ is alkyl, perfluoroalkyl, halo, cyano, or CO₂alkyl; R² is optionally substituted alkyl, cycloalkyl, heterocycloalkyl, or spiroheterocycloalkyl; R³ is optionally substituted aryl. R⁴ is optionally substituted alkyl, cycloalkyl, or heterocycloalkyl; R⁵ is hydrogen or alkyl; R⁶ is optionally substituted aryl or heteroaryl; R⁷ is alkyl, perfluoroalkyl, halo, cyano, or alkoxycarbonyl; and X is absent or SO₂.
  [FR] L'invention concerne des composés de sulfamides d'indole ou des sels pharmaceutiquement acceptables de ceux-ci, qui sont des modulateurs de la protéine 1 SFRP (secreted frizzled related protein). Les composés et les compositions contenant les composés peuvent être utilisés pour traiter divers troubles comprenant l'ostéoporose.
• Novel Bis(1<i>H</i>-indol-2-yl)methanones as Potent Inhibitors of FLT3 and Platelet-Derived Growth Factor Receptor Tyrosine Kinase
  作者：Siavosh Mahboobi、Andrea Uecker、Andreas Sellmer、Christophe Cénac、Heymo Höcher、Herwig Pongratz、Emerich Eichhorn、Harald Hufsky、Antje Trümpler、Marit Sicker、Florian Heidel、Thomas Fischer、Carol Stocking、Sigurd Elz、Frank-D. Böhmer、Stefan Dove

  DOI：10.1021/jm058033i

  日期：2006.6.1

  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.