5,6,8,9-四氢-2-硝基-7H-苯并-7-环庚酮 | 740842-50-6

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 中文名称: 5,6,8,9-四氢-2-硝基-7H-苯并-7-环庚酮
• 中文别名: 2-硝基-5,6,8,9-四氢-苯并7-环庚酮；2-硝基-8,9-二氢-5H-苯并[7]轮烯-7(6H)-酮
• 英文名称: 2-nitro-5,6,8,9-tetrahydrobenzo[7]annulen-7-one
• 英文别名: 2-Nitro-8,9-dihydro-5H-benzo[7]annulen-7(6H)-one；3-nitro-5,6,8,9-tetrahydrobenzo[7]annulen-7-one
• CAS: 740842-50-6
• 化学式: C₁₁H₁₁NO₃
• 分子量: 205.213
• InChiKey: YQPLEYWTKAXWAD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  62.9
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 储存条件：
  存放于室温、避光且在惰性气体环境中

反应信息

• 作为反应物：
  描述：

  5,6,8,9-四氢-2-硝基-7H-苯并-7-环庚酮 在 palladium on activated charcoal 、 氢气 、 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 甲醇 、 1,2-二氯乙烷 、 异丙醇 为溶剂， 生成 1-(6,7-二氢-5H-苯并[6,7]环庚烷并[1,2-c]哒嗪-3-基)-N3-[(7S)-6,7,8,9-四氢-7-(1-吡咯烷基)-5H-苯并环庚烯-2-基]-1H-1,2,4-三唑-3,5-二胺
  参考文献：
  名称：

  Bemcentinib. Tyrosine-protein kinase receptor UFO (Axl) inhibitor, Treatment of cancer

  摘要：

  Increased expression of Axl has been reported in various cancers including colon, esophageal, thyroid, breast, lung, liver and astrocytoma-glioblastoma. Cancer resistance to tyrosine kinase inhibitors and other chemotherapeutics has been correlated with aberrant expression of Axl. These findings support the development of Axl inhibitors in combination with targeted agents to tackle acquired resistance and high Axl levels. Bemcentinib (BGB-324, R-428) is an oral, potent and selective small-molecule inhibitor of Axl kinase in vitro with IC50 values in the low nanomolar range. In preclinical studies, bemcentinib demonstrated efficacy across multiple cancer models. It has also shown a favorable safety profile in clinical studies in cancer patients, and encouraging activity in acute myeloid leukemia (AML) and non-small cell lung cancer (NSCLC). Currently, there are phase II studies with bemcentinib ongoing in advanced NSCLC, triple-negative breast cancer, AML and myelodysplastic syndromes, and metastatic melanoma. Orphan drug designation was granted by the U.S. Food and Drug Administration for the treatment of AML.

  DOI：

  10.1358/dof.2018.043.09.2808543
• 作为产物：
  描述：

  5,6,8,9-四氢-苯并环庚烯-7-酮 在 硫酸 、 potassium nitrate 作用下， 以79 %的产率得到5,6,8,9-四氢-2-硝基-7H-苯并-7-环庚酮
  参考文献：
  名称：

  [EN] TRICYCLIC HPK1 INHIBITOR AND USE THEREOF
  [FR] INHIBITEUR DE HPK1 TRICYCLIQUE ET SON UTILISATION
  [ZH] 三并环类HPK1抑制剂及其用途

  摘要：

  本发明属于医药技术领域，具体涉及一类三并环类HPK1抑制剂化合物、其药学上可接受的盐或其立体异构体，含有所述化合物、其药学上可接受的盐或其异构体的药物组合物及制剂，制备所述化合物、其药学上可接受的盐或其立体异构体的方法，以及所述化合物、其药学上可接受的盐或其立体异构体的用途。

  公开号：

  WO2022188823A1

文献信息

• AXL INHIBITORS FOR USE IN COMBINATION THERAPY FOR PREVENTING, TREATING OR MANAGING METASTATIC CANCER
  申请人：Rigel Pharmaceuticals, Inc.

  公开号：US20190336500A1

  公开（公告）日：2019-11-07

  This invention is directed to methods of preventing, treating or managing cancer, preferably metastatic cancer, in a patient. The methods comprise administering an effective amount of an Axl inhibitor in combination with the administration of an effective amount of one or more chemotherapeutic agents.

  这项发明旨在针对患者预防、治疗或管理癌症，最好是转移性癌症的方法。该方法包括在给予有效剂量的Axl抑制剂的同时，联合给予一个或多个化疗药物的有效剂量。
• [EN] OXAZOLIDINONE DERIVATIVES N-SUBSTITUTED BY A BICYCLIC RING, FOR USE AS ANTIBACTERIAL AGENTS<br/>[FR] DERIVES D'OXAZOLIDINONE N-SUBSTITUES PAR UN NOYAU BICYCLIQUE, UTILISES COMME AGENTS ANTIBACTERIENS
  申请人：WARNER LAMBERT CO

  公开号：WO2004069244A1

  公开（公告）日：2004-08-19

  Compounds of formula (I) and methods for their preparation are disclosed. Further disclosed are methods of making biologically active compounds of formula (I) as well as pharmaceutically acceptable compositions comprising compounds of formula (I). Compounds of formula (I) as disclosed herein can be used in a variety of applications including use as antibacterial agents. P is a bicyclic ring system as defined in claim 1.

  公式（I）的化合物及其制备方法已被披露。进一步披露了制备公式（I）生物活性化合物的方法，以及包含公式（I）化合物的药用可接受组合物的方法。本文披露的公式（I）化合物可用于各种应用，包括用作抗菌剂。P是如权利要求1所定义的双环环系统。
• [EN] BRIDGED BICYCLIC HETEROARYL SUBSTITUTED TRIAZOLES USEFUL AS AXL INHIBITORS<br/>[FR] TRIAZOLES SUBSTITUÉS PAR HÉTÉROARYLE BICYCLIQUES PONTÉS UTILES COMME INHIBITEURS DE AXL
  申请人：RIGEL PHARMACEUTICALS INC

  公开号：WO2010005879A1

  公开（公告）日：2010-01-14

  Bridged bicyclic heteroaryl substituted triazoles and pharmaceutical compositions containing the compounds are disclosed as being useful in inhibiting the activity of the receptor protein tyrosine kinase AxI. Methods of using the compounds in treating diseases or conditions associated with AxI activity are also disclosed.

  本文披露了桥接的双环杂环取代三唑和含有这些化合物的药物组合物，可用于抑制受体蛋白酪氨酸激酶AxI的活性。还披露了使用这些化合物治疗与AxI活性相关的疾病或病况的方法。
• Structure–Affinity Relationships of 2,3,4,5-Tetrahydro-1<i>H</i>-3-benzazepine and 6,7,8,9-Tetrahydro-5<i>H</i>-benzo[7]annulen-7-amine Analogues and the Discovery of a Radiofluorinated 2,3,4,5-Tetrahydro-1<i>H</i>-3-benzazepine Congener for Imaging GluN2B Subunit-Containing <i>N</i>-Methyl-<scp>d</scp>-aspartate Receptors
  作者：Hazem Ahmed、Ahmed Haider、Jasmine Varisco、Maja Stanković、Rahel Wallimann、Stefan Gruber、Irina Iten、Surya Häne、Adrienne Müller Herde、Claudia Keller、Roger Schibli、Dirk Schepmann、Linjing Mu、Bernhard Wünsch、Simon M. Ametamey

  DOI：10.1021/acs.jmedchem.9b00812

  日期：2019.11.14

  Aspiring to develop a positron emission tomography (PET) imaging agent for the GluN2B subunits of the N-methyl-d-aspartate receptor (NMDAR), a key therapeutic target for drug development toward several neurological disorders, we synthesized a series of 2,3,4,5-tetrahydro-1H-3-benzazepine and 6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-amine analogues. After in vitro testing via competition binding assay

  渴望开发一种正电子发射断层摄影（PET）成像剂用于的GluN2B亚基Ñ甲基d天冬氨酸受体（NMDAR），用于药物开发的朝向几个神经病症的关键的治疗靶，我们合成了一系列的2,3 ，4，5-四氢-1 H -3-苯并ze庚因和6,7,8,9-四氢-5 H-苯并[7] Annulen-7-胺类似物。通过竞争结合测定和放射自显影进行体外测试后，[ 18就对σ1和σ2受体的特异性和选择性而言，F] PF-NB1成为表现最佳的示踪剂，因此被选择用于进一步的体内评估。铜介导的放射性氟化以良好的放射化学收率和较高的摩尔活度完成。在Wistar大鼠中进行了广泛的体内表征，包括PET成像，生物分布，受体占有率和代谢产物研究。[ 18 F] PF-NB1结合对富含GluN2B的前脑区域具有选择性，并且被GluN2B拮抗剂CP-101606特异性阻断，没有剂量依赖性，且没有脑放射性代谢物。[ 18 F] PF-NB1是一种很有前途的氟18
• Design, Synthesis, Pharmacological Evaluation and Docking Studies of GluN2B-Selective NMDA Receptor Antagonists with a Benzo[7]annulen-7-amine Scaffold
  作者：Sandeep Gawaskar、Louisa Temme、Julian A. Schreiber、Dirk Schepmann、Alessandro Bonifazi、Dina Robaa、Wolfgang Sippl、Nathalie Strutz-Seebohm、Guiscard Seebohm、Bernhard Wünsch

  DOI：10.1002/cmdc.201700311

  日期：2017.8.8

  Antagonists that selectively target GluN2B-subunit-containing N-methyl-d-aspartate (NMDA) receptors are of major interest for the treatment of various neurological disorders. In this study, relationships between variously substituted benzo[7]annulen-7-amines and their GluN2B affinity were investigated. 2-Nitro-5,6,8,9-tetrahydrobenzo[7]annulen-7-one (8) represents the central building block for the

  选择性靶向含GluN2B亚基的N-甲基-d-天冬氨酸（NMDA）受体的拮抗剂是治疗各种神经系统疾病的主要兴趣。在这项研究中，研究了各种取代的苯并[7]年环七胺与它们的GluN2B亲和力之间的关系。2-硝基-5,6,8,9-四氢苯并[7]环戊烯-7-（8）表示在2位上引入各种取代基和各种7-氨基部分的中心结构单元。具有2-NO 2（7 c），2-Cl（15 c）或2-的N-（3-苯基丙基）-6,7,8,9-四氢-5H-苯并[7]年戊烯-7-胺OBn组（22 c）显示出很高的GluN2B亲和力（Ki = 1.6-3.6 nm）。对接研究表明，在GluN1b和GluN2B亚基的界面上，苯并[7]环戊烯7-胺和艾芬地尔具有相同的结合姿势。22 c的较大的2-OBn部分占据了以前无法识别的子口袋，这解释了其较高的GluN2B亲和力（Ki = 3.6 nm）。在两电极电压钳实验和细胞保护试验中，高亲和