1-(2-nitro-6,7,8,9-tetrahydro-5H-benzo[7]annulene-7-yl)pyrrolidine | 1037627-93-2

• 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
• 英文名称: 1-(2-nitro-6,7,8,9-tetrahydro-5H-benzo[7]annulene-7-yl)pyrrolidine
• 英文别名: 1-(2-nitro-6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl)pyrrolidine；1-(3-nitro-6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl)pyrrolidine
• CAS: 1037627-93-2
• 化学式: C₁₅H₂₀N₂O₂
• 分子量: 260.336
• InChiKey: HTMSXWOFIDKOON-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  19
• 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：
  49.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-nitro-6,7,8,9-tetrahydro-5H-benzo[7]annulene-7-yl)pyrrolidine 在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 、 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-2-硝基-7H-苯并-7-环庚酮 以85的产率得到1-(2-nitro-6,7,8,9-tetrahydro-5H-benzo[7]annulene-7-yl)pyrrolidine
  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，给予一种Axl抑制剂的有效剂量。

  公开号：

  US20170042891A1

文献信息

• 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。
• SUBSTITUTED TRIAZOLES USEFUL AS AXL INHIBITORS
  申请人：Goff Dane

  公开号：US20080188474A1

  公开（公告）日：2008-08-07

  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.

  本发明揭示了替代三唑和含有该化合物的制药组合物，其在抑制受体蛋白酪氨酸激酶Axl的活性方面是有用的。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。
• Polycyclic heteroaryl substituted triazoles useful as Axl inhibitors
  申请人：Rigel Pharmaceuticals, Inc.

  公开号：US08168636B2

  公开（公告）日：2012-05-01

  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.

  本文披露了多环杂芳基取代的三唑和含有该化合物的药物组合物，其可用于抑制受体蛋白酪氨酸激酶Axl的活性。同时，本文还披露了使用该化合物治疗与Axl活性相关的疾病或病况的方法。