1-[6,7-Bis(difluoromethoxy)naphthalen-2-yl]-2-methyl-1-[1-(2-trimethylsilylethoxymethyl)triazol-4-yl]propan-1-ol | 1375603-92-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-[6,7-Bis(difluoromethoxy)naphthalen-2-yl]-2-methyl-1-[1-(2-trimethylsilylethoxymethyl)triazol-4-yl]propan-1-ol
• 英文别名: 1-[6,7-bis(difluoromethoxy)naphthalen-2-yl]-2-methyl-1-[1-(2-trimethylsilylethoxymethyl)triazol-4-yl]propan-1-ol
• CAS: 1375603-92-1
• 化学式: C₂₄H₃₁F₄N₃O₄Si
• 分子量: 529.607
• InChiKey: PCWBZTNYBKKKJM-UHFFFAOYSA-N

物化性质

• 沸点：
  577.1±60.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.84
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  78.6
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1-[6,7-Bis(difluoromethoxy)naphthalen-2-yl]-2-methyl-1-[1-(2-trimethylsilylethoxymethyl)triazol-4-yl]propan-1-ol 在 四丁基氟化铵 、 cesium fluoride 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 赛维罗奈
  参考文献：
  名称：

  Highly-selective 4-(1,2,3-triazole)-based P450c17a 17,20-lyase inhibitors

  摘要：

  The orally-active CYP17A1 inhibitor abiraterone acetate (AA) decreases adrenal and intratumoral androgen biosynthesis and is an effective agent for the treatment of prostate cancer. Abiraterone potently inhibits both reactions catalyzed by CYP17, the 17 alpha-hydroxylase (hydroxylase) reaction as well as the 17,20-lyase (lyase) transformation. CYP17 hydroxylase inhibition prevents the synthesis of adrenal glucocorticoids and causes an accumulation of circulating mineralocorticoids. As a consequence of potent CYP17 hydroxylase inhibition (i.e., lack of lyase selectivity), AA must be co-administered with the cortisol replacement prednisone and patients may experience the effects of mineralocorticoid excess syndrome (MES). Herein, we describe rationally-designed, CYP17 lyase-selective inhibitors that could prove safer and more effective than abiraterone. Using proprietary methodology, the high-affinity pyridine or imidazole metal-binding group found in current clinical CYP17 inhibitors was replaced with novel, less avid, metal-binding groups in concert with potency-enhancing molecular scaffold modifications. This process produced a unique series of CYP17 lyase-selective inhibitors that included the oral agent 6 (VT-464), now in Phase 2 prostate cancer clinical trials. The chemical methodology described is potentially applicable to the design of new and more effective metalloenzyme inhibitor treatments for a broad array of diseases. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.024
• 作为产物：
  描述：

  2,3-二甲氧基萘 在 aluminum (III) chloride 、 叔丁基锂 、 三溴化硼 、 potassium carbonate 作用下， 以 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 52.0h， 生成 1-[6,7-Bis(difluoromethoxy)naphthalen-2-yl]-2-methyl-1-[1-(2-trimethylsilylethoxymethyl)triazol-4-yl]propan-1-ol
  参考文献：
  名称：

  Highly-selective 4-(1,2,3-triazole)-based P450c17a 17,20-lyase inhibitors

  摘要：

  The orally-active CYP17A1 inhibitor abiraterone acetate (AA) decreases adrenal and intratumoral androgen biosynthesis and is an effective agent for the treatment of prostate cancer. Abiraterone potently inhibits both reactions catalyzed by CYP17, the 17 alpha-hydroxylase (hydroxylase) reaction as well as the 17,20-lyase (lyase) transformation. CYP17 hydroxylase inhibition prevents the synthesis of adrenal glucocorticoids and causes an accumulation of circulating mineralocorticoids. As a consequence of potent CYP17 hydroxylase inhibition (i.e., lack of lyase selectivity), AA must be co-administered with the cortisol replacement prednisone and patients may experience the effects of mineralocorticoid excess syndrome (MES). Herein, we describe rationally-designed, CYP17 lyase-selective inhibitors that could prove safer and more effective than abiraterone. Using proprietary methodology, the high-affinity pyridine or imidazole metal-binding group found in current clinical CYP17 inhibitors was replaced with novel, less avid, metal-binding groups in concert with potency-enhancing molecular scaffold modifications. This process produced a unique series of CYP17 lyase-selective inhibitors that included the oral agent 6 (VT-464), now in Phase 2 prostate cancer clinical trials. The chemical methodology described is potentially applicable to the design of new and more effective metalloenzyme inhibitor treatments for a broad array of diseases. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.024

文献信息

• [EN] COMPOSITIONS FOR THE TREATMENT OF BRAIN TUMORS<br/>[FR] COMPOSITIONS DESTINÉES AU TRAITEMENT DE TUMEURS CÉRÉBRALES
  申请人：INNOCRIN PHARMACEUTICALS INC

  公开号：WO2019182743A1

  公开（公告）日：2019-09-26

  The instant invention describes pharmaceutical compositions and dosing regimens comprising seviteronel and/or dexamethasone, and methods of treating diseases, disorders symptoms thereof.

  这项即时发明描述了包含赛维特龙和/或地塞米松的药物组合物和给药方案，以及治疗疾病、疾病症状的方法。
• [EN] COMPOSITIONS FOR THE TREATMENT OF BRAIN TUMORS<br/>[FR] COMPOSITIONS POUR LE TRAITEMENT DE TUMEURS CÉRÉBRALES
  申请人：INNOCRIN PHARMACEUTICALS INC

  公开号：WO2020077197A1

  公开（公告）日：2020-04-16

  The instant invention describes pharmaceutical compositions and dosing regimens comprising radiation therapy and seviteronel with or without dexamethasone, and methods of treating diseases, disorders or symptoms thereof.

  这项即时发明描述了包括放射治疗和赛维特鲁内尔在内或不包括地塞米松的药物组合物和给药方案，以及治疗疾病、疾病或症状的方法。
• [EN] COMPOSITIONS FOR THE TREATMENT OF BREAST AND PROSTATE CANCER<br/>[FR] COMPOSITIONS POUR LE TRAITEMENT DU CANCER DU SEIN ET DE LA PROSTATE
  申请人：INNOCRIN PHARMACEUTICALS INC

  公开号：WO2019113301A1

  公开（公告）日：2019-06-13

  The instant invention describes pharmaceutical compositions and dosing regimens comprising seviteronel and/or dexamethasone, and methods of treating diseases, disorders or symptoms thereof.

  本发明描述了包含seviteronel和/或地塞米松的药物组合物和给药方案，以及治疗疾病、疾病或症状的方法。
• [EN] METHODS OF TREATING CANCER USING ANDROGEN RECEPTOR ANTAGONISTS<br/>[FR] MÉTHODES DE TRAITEMENT DU CANCER À L'AIDE D'ANTAGONISTES DE RÉCEPTEURS DES ANDROGÈNES
  申请人：GARVAN INSTITUTE OF MEDICAL RES

  公开号：WO2021077174A1

  公开（公告）日：2021-04-29

  Disclosed herein are methods of sensitizing cancer cells to an anticancer agent, methods of inhibiting the development of resistance of a cancer cell to an anticancer agent, and methods of inhibiting cancer cell proliferation, each comprising administering an androgen receptor antagonist. Also disclosed herein are methods of determining the prognosis of a subject suffering from cancer, methods of selecting a subject for therapy with an anti-cancer agent and methods of predicting a subject's response to an anti-cancer agent, each comprising determining the level of expression and/or activity of the androgen receptor and/or ZEB1 in the cytoplasm.

  本文揭示了一种使癌细胞对抗癌药物敏感的方法，一种抑制癌细胞对抗癌药物产生耐药性的方法，以及一种抑制癌细胞增殖的方法，每种方法包括给予雄激素受体拮抗剂。本文还揭示了一种确定患癌症主题的预后的方法，一种选择受治疗对象的抗癌药物疗法的方法，以及一种预测受治疗对象对抗癌药物反应的方法，每种方法包括确定细胞质中雄激素受体和/或ZEB1的表达水平和/或活性。
• METALLOENZYME INHIBITOR COMPOUNDS
  申请人：Innocrin Pharmaceuticals, Inc.

  公开号：US20170143694A1

  公开（公告）日：2017-05-25

  The instant invention describes compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.

  本发明描述了具有金属酶调节活性的化合物，以及治疗由这些金属酶介导的疾病、疾病或症状的方法。