1-(3-(4-fluorophenoxy)propyl)-3-(4-chlorophenyl)guanidine | 1541941-57-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-(3-(4-fluorophenoxy)propyl)-3-(4-chlorophenyl)guanidine
• 英文别名: 1-(4-chlorophenyl)-3-(3-(4-fluorophenoxy)propyl)guanidine；1-(4-Chlorophenyl)-2-[3-(4-fluorophenoxy)propyl]guanidine；1-(4-chlorophenyl)-2-[3-(4-fluorophenoxy)propyl]guanidine
• CAS: 1541941-57-4
• 化学式: C₁₆H₁₇ClFN₃O
• 分子量: 321.782
• InChiKey: YIXQZLPGNXXTFM-UHFFFAOYSA-N

物化性质

• 沸点：
  442.0±55.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  59.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  S-methyl-(4-chlorophenyl)isothiourea 、 3-(4-氟苯氧基)-1-丙胺 以 乙醇 为溶剂， 反应 12.0h， 以78%的产率得到1-(3-(4-fluorophenoxy)propyl)-3-(4-chlorophenyl)guanidine
  参考文献：
  名称：

  Novel small molecule guanidine Sigma1 inhibitors for advanced prostate cancer

  摘要：

  Prostate cancer is the most frequently diagnosed malignancy and the leading cause of cancer related death in men. First line therapy for disseminated disease relies on androgen deprivation, leveraging the addiction of these tumors on androgens for both growth and survival. Treatment typically involves antagonizing the androgen receptor (AR) or blocking the synthesis of androgens. Recurrence is common and within 2-3 years patients develop castration resistant tumors that become unresponsive to AR-axis targeted therapies. In order to provide a more effective treatment, we are utilizing an approach that targets a key scaffolding protein, Sigma1 (also known as sigma-1 receptor), a unique 26-kilodalton integral membrane protein that is critical in stabilizing the AR. Herein we report on a new series of Sigmal compounds for lead optimization derived from a hybrid pharmacophore approach. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.03.030

文献信息

• Sigma receptor ligands and methods of modulating cellular protein homeostasis using same
  申请人：DREXEL UNIVERSITY

  公开号：US10314795B2

  公开（公告）日：2019-06-11

  The present invention includes compounds useful in preventing, treating or ameliorating Sigma-related disorders or diseases. The compounds of the invention may modulate cellular protein homeostasis, which includes: translation initiation, folding, processing, transport, and degradation (including ubiquitin selective autophagy) of proteins. The present invention also includes methods of preventing, treating or ameliorating a Sigma-related disorder or disease in a subject in need thereof, the method comprising administering to the subject an effective amount of a Sigma-modulating compound. The present invention also includes methods of preventing, treating or ameliorating a Sigma-related disorder or disease in a subject in need thereof, the method comprising administering to the subject an effective amount of a Sigma-modulating compound, further comprising administering an effective amount of a compound that inhibits the ubiquitin proteasome system (UPS) and/or autophagic survival pathways.

  本发明包括可用于预防、治疗或改善西格玛相关紊乱或疾病的化合物。本发明的化合物可调节细胞蛋白质的平衡，其中包括：蛋白质的翻译起始、折叠、加工、运输和降解（包括泛素选择性自噬）。本发明还包括预防、治疗或改善有需要的受试者与 Sigma 相关的失调或疾病的方法，该方法包括向受试者施用有效量的 Sigma 调节化合物。本发明还包括预防、治疗或改善有需要的受试者的西格玛相关紊乱或疾病的方法，该方法包括向受试者施用有效量的西格玛调节化合物，进一步包括施用有效量的抑制泛素蛋白酶体系统（UPS）和/或自噬存活途径的化合物。
• NOVEL SIGMA RECEPTOR LIGANDS AND METHODS OF MODULATING CELLULAR PROTEIN HOMEOSTASIS USING SAME
  申请人：Drexel University

  公开号：EP2874997A2

  公开（公告）日：2015-05-27
• METHODS OF IDENTIFYING AND TREATING TUMORS WITH SIGMA1 INHIBITORS
  申请人：DREXEL UNIVERSITY

  公开号：US20200087730A1

  公开（公告）日：2020-03-19

  Methods and uses of using Sigma1 inhibitors are provide herein, including diagnostic methods for predicting or identifying quantitatively whether a human tumor is responsive or non-responsive to treatment with Sigma1 inhibition are also provided.
• US9388126B2
  申请人：——

  公开号：US9388126B2

  公开（公告）日：2016-07-12
• US9889102B2
  申请人：——

  公开号：US9889102B2

  公开（公告）日：2018-02-13