tert-butyl (1-(phenylsulfonyl)-1H-indol-5-yl)carbamate | 1345012-46-5

• 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: tert-butyl (1-(phenylsulfonyl)-1H-indol-5-yl)carbamate
• 英文别名: tert-butyl N-[1-(benzenesulfonyl)indol-5-yl]carbamate
• CAS: 1345012-46-5
• 化学式: C₁₉H₂₀N₂O₄S
• 分子量: 372.445
• InChiKey: XVIVIOMTXFHXAN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  85.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (1-(phenylsulfonyl)-1H-indol-5-yl)carbamate 在 叔丁基锂 、 三乙酰氧基硼氢化钠 、 potassium carbonate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 溶剂黄146 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 水 、 1,2-二氯乙烷 为溶剂， 反应 23.08h， 生成 (5-(1-((2-((4-methoxybenzyl)(pyridin-2-yl)amino)ethyl)(methyl)amino)propan-2-ylamino)-1H-indol-2-yl)(4-methylpiperazin-1-yl)methanone
  参考文献：
  名称：

  Mepyramine–JNJ7777120-hybrid compounds show high affinity to hH1R, but low affinity to hH4R

  摘要：

  In literature, a synergism between histamine H-1 and H-4 receptor is discussed. Furthermore, it was shown, that the combined application of mepyramine, a H-1 antagonist and JNJ7777120, a H-4 receptor ligand leads to a synergistic effect in the acute murine asthma model. Thus, the aim of this study was to develop new hybrid ligands, containing one H-1 and one H-4 pharmacophor, connected by an appropriate spacer, in order to address both, H1R and H4R. Within this study, we synthesized nine hybrid compounds, which were pharmacologically characterized at hH(1)R and hH(4)R. The new compounds revealed (high) affinity to hH(1)R, but showed only low affinity to hH(4)R. Additionally, we performed molecular dynamic studies for some selected compounds at hH(1)R, in order to obtain information about the binding mode of these compounds on molecular level. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.001
• 作为产物：
  描述：

  吲哚啉 在 4-二甲氨基吡啶 、 manganese(IV) oxide 、 tin(II) chloride dihdyrate 、 硝酸 、 三乙胺 作用下， 以 四氢呋喃 、 硝基甲烷 、 乙醇 、 二氯甲烷 为溶剂， 反应 43.0h， 生成 tert-butyl (1-(phenylsulfonyl)-1H-indol-5-yl)carbamate
  参考文献：
  名称：

  Mepyramine–JNJ7777120-hybrid compounds show high affinity to hH1R, but low affinity to hH4R

  摘要：

  In literature, a synergism between histamine H-1 and H-4 receptor is discussed. Furthermore, it was shown, that the combined application of mepyramine, a H-1 antagonist and JNJ7777120, a H-4 receptor ligand leads to a synergistic effect in the acute murine asthma model. Thus, the aim of this study was to develop new hybrid ligands, containing one H-1 and one H-4 pharmacophor, connected by an appropriate spacer, in order to address both, H1R and H4R. Within this study, we synthesized nine hybrid compounds, which were pharmacologically characterized at hH(1)R and hH(4)R. The new compounds revealed (high) affinity to hH(1)R, but showed only low affinity to hH(4)R. Additionally, we performed molecular dynamic studies for some selected compounds at hH(1)R, in order to obtain information about the binding mode of these compounds on molecular level. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.001

文献信息

• [EN] SYNTHESIS, PHARMACOLOGY AND USE OF NEW AND SELECTIVE FMS-LIKE TYROSINE KINASE 3 (FLT3) FLT3 INHIBITORS<br/>[FR] SYNTHÈSE, PHARMACOLOGIE ET UTILISATION DE NOUVEAUX INHIBITEURS SÉLECTIFS DE LA TYROSINE KINASE 3 DE TYPE FMS FLT3 (FLT3)
  申请人：UNIV REGENSBURG

  公开号：WO2019034538A1

  公开（公告）日：2019-02-21

  The present invention relates to small molecule compounds of formula (I) and their use as FLT3 inhibitors for the treatment of various diseases, such as acute myeloid leukemia (AML). The present invention further relates to methods of synthesizing the compounds and methods of treatment.

  本发明涉及式(I)的小分子化合物及其作为FLT3抑制剂用于治疗各种疾病，如急性髓系白血病（AML）。本发明还涉及合成这些化合物的方法和治疗方法。
• Synthesis, pharmacology and use of new and selective FMS-like tyrosine kinase 3 (FLT3) FLT3 inhibitors
  申请人：UNIVERSITÄT REGENSBURG

  公开号：US11384076B2

  公开（公告）日：2022-07-12

  The present invention relates to small molecule compounds of formula (I) and their use as FLT3 inhibitors for the treatment of various diseases, such as acute myeloid leukemia (AML). The present invention further relates to methods of synthesizing the compounds and methods of treatment.

  本发明涉及式（I）的小分子化合物及其作为FLT3抑制剂用于治疗各种疾病，如急性髓性白血病（AML）。本发明进一步涉及化合物的合成方法和治疗方法。
• A series of novel aryl-methanone derivatives as inhibitors of FMS-like tyrosine kinase 3 (FLT3) in FLT3-ITD-positive acute myeloid leukemia
  作者：Andreas Sellmer、Bernadette Pilsl、Mandy Beyer、Herwig Pongratz、Lukas Wirth、Sigurd Elz、Stefan Dove、Sven Julian Henninger、Karsten Spiekermann、Harald Polzer、Susan Klaeger、Bernhard Kuster、Frank D. Böhmer、Heinz-Herbert Fiebig、Oliver H. Krämer、Siavosh Mahboobi

  DOI：10.1016/j.ejmech.2020.112232

  日期：2020.5

  Mutants of the FLT3 receptor tyrosine kinase (RTK) with duplications in the juxtamembrane domain (FLT3-ITD) act as drivers of acute myeloid leukemia (AML). Potent tyrosine kinase inhibitors (TKi) of FLT3-ITD entered clinical trials and showed a promising, but transient success due to the occurrence of secondary drug-resistant AML clones. A further caveat of drugs targeting FLT3-ITD is the co-targeting of other RTKs which are required for normal hematopoiesis. This is observed quite frequently. Therefore, novel drugs are necessary to treat AML effectively and safely. Recently bis(1H-indol-2-yl)methanones were found to inhibit FLT3 and PDGFR kinases. In order to optimize these agents we synthesized novel derivatives of these methanones with various substituents. Methanone 16 and its carbamate derivative 17b inhibit FLT3-ITD at least as potently as the TKi AC220 (quizartinib). Models indicate corresponding interactions of 16 and quizartinib with FLT3. The activity of 16 is accompanied by a high selectivity for FLT3-ITD. (c) 2020 Elsevier Masson SAS. All rights reserved.
• SYNTHESIS, PHARMACOLOGY AND USE OF NEW AND SELECTIVE FMS-LIKE TYROSINE KINASE 3 (FLT3) FLT3 INHIBITORS
  申请人：UNIVERSITÄT REGENSBURG

  公开号：US20200190075A1

  公开（公告）日：2020-06-18

  The present invention relates to small molecule compounds of formula (I) and their use as FLT3 inhibitors for the treatment of various diseases, such as acute myeloid leukemia (AML). The present invention further relates to methods of synthesizing the compounds and methods of treatment.