7-(吡咯烷-1-基)-6,7,8,9-四氢-5H-苯并[7]轮烯-2-胺 | 1037627-94-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 7-(吡咯烷-1-基)-6,7,8,9-四氢-5H-苯并[7]轮烯-2-胺
• 英文名称: 7-(pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-amine
• 英文别名: 1-(2-amino-6,7,8,9-tetrahydro-5H-benzo[7]annulene-7-yl)pyrrolidine；7-pyrrolidin-1-yl-6,7,8,9-tetrahydro-5H-benzo[7]annulen-3-amine
• CAS: 1037627-94-3
• 化学式: C₁₅H₂₂N₂
• 分子量: 230.353
• InChiKey: QYLOOOSMNDHSEP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  7-(吡咯烷-1-基)-6,7,8,9-四氢-5H-苯并[7]轮烯-2-胺 以 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：

  1-(2-nitro-6,7,8,9-tetrahydro-5H-benzo[7]annulene-7-yl)pyrrolidine 在 钯 氢气 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以to afford 7-(pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-amine as an oil (quantitative yield)的产率得到7-(吡咯烷-1-基)-6,7,8,9-四氢-5H-苯并[7]轮烯-2-胺
  参考文献：
  名称：

  AXL INHIBITORS FOR USE IN COMBINATION THERAPY FOR PREVENTING, TREATING OR MANAGING METASTATIC CANCER

  摘要：

  本发明旨在提供一种用于预防、治疗或管理患者的癌症，特别是转移性癌症的方法。该方法包括在给予一种或多种化疗药物的有效剂量的同时，给予有效剂量的Axl抑制剂的组合。

  公开号：

  US20130338161A1

文献信息

• [EN] HETEROCYCLIC COMPOUNDS AS AXL INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES EN TANT QU'INHIBITEURS D'AXL
  申请人：CHANGZHOU JIEKAI PHARMATECH CO LTD

  公开号：WO2015143692A1

  公开（公告）日：2015-10-01

  Compounds of Formula I and their uses of effective AXL inhibitors and for the treatment of physical condition mediated by AXL.

  Formula I的化合物及其用途是有效的AXL抑制剂，用于治疗由AXL介导的身体状况。
• 一类多取代的吡嗪/三嗪酰胺类化合物及其制备方法和应用
  申请人：中国科学院上海药物研究所

  公开号：CN109384774B

  公开（公告）日：2023-02-17

  本发明公开了一类多取代的吡嗪/三嗪酰胺类化合物及其制备方法和应用，该多取代的吡嗪/三嗪酰胺类化合物的结构如通式I所示，各取代基的定义如说明书和权利要求书所述。本发明的多取代的吡嗪/三嗪酰胺类化合物具有卓越的AXL抑制活性，能够用作AXL抑制剂。
• POLYCYCLIC HETEROARYL SUBSTITUTED TRIAZOLES USEFUL AS AXL INHIBITORS
  申请人：RIGEL PHARMACEUTICALS, INC.

  公开号：US20140323490A1

  公开（公告）日：2014-10-30

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

  本发明涉及多环杂芳基取代的三唑化合物以及含有这些化合物的制药组合物，这些化合物被揭示为在抑制受体蛋白酪氨酸激酶Axl的活性方面有用。还揭示了使用这些化合物治疗与Axl活性相关的疾病或病状的方法。
• [EN] AXL INHIBITORS FOR USE IN COMBINATION THERAPY FOR PREVENTING, TREATING OR MANAGING METASTATIC CANCER<br/>[FR] INHIBITEURS DE AXL POUR UNE UTILISATION DANS UNE THÉRAPIE DE COMBINAISON POUR PRÉVENIR, TRAITER OU GÉRER UN CANCER MÉTASTASIQUE
  申请人：RIGEL PHARMACEUTICALS INC

  公开号：WO2010083465A1

  公开（公告）日：2010-07-22

  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 AxI inhibitor in combination with the administation of an effective amount of one or more chemotherapeutic agents.

  本发明涉及一种预防、治疗或管理患者癌症，特别是转移性癌症的方法。该方法包括在给患者适当剂量的AxI抑制剂的同时，与一个或多个化疗药物的适当剂量联合使用。
• POLYCYCLIC HETEROARYL SUBSTITUTED TRIAZOLES USEFUL AS AXL INHIBITORS
  申请人：Goff Dane

  公开号：US20080188455A1

  公开（公告）日：2008-08-07

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

  本发明揭示了多环杂芳基取代的三唑类化合物及含有该化合物的制药组合物，用于抑制受体蛋白酪氨酸激酶Axl的活性。还揭示了使用该化合物治疗与Axl活性相关的疾病或病况的方法。