N-((3R)-1-[(6-fluoro-2-naphthyl)methyl]pyrrolidin-3-yl)-2-(4-phenoxycyclohexylidene)acetamide | 671204-30-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-((3R)-1-[(6-fluoro-2-naphthyl)methyl]pyrrolidin-3-yl)-2-(4-phenoxycyclohexylidene)acetamide
• CAS: 671204-30-1
• 化学式: C₂₉H₃₁FN₂O₂
• 分子量: 458.576
• InChiKey: BLIXSIRUUZYDMW-ADPJQGBTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.62
• 重原子数：
  34.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  41.57
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  diethyl[2-({(3E)-1-[(6-fluoro-2-naphthyl)methyl]-pyrrolidin-3-yl}amino)-2-oxoethyl]phosphonate 、 4-苯氧基环己酮 在 sodium hydride 作用下， 以 乙二醇二甲醚 、 mineral oil 为溶剂， 反应 3.5h， 以79%的产率得到N-((3R)-1-[(6-fluoro-2-naphthyl)methyl]pyrrolidin-3-yl)-2-(4-phenoxycyclohexylidene)acetamide
  参考文献：
  名称：

  Synthesis, biological evaluation, and metabolic stability of acrylamide derivatives as novel CCR3 antagonists

  摘要：

  Our laboratory has identified several acrylamide derivatives with potent CCR3 inhibitory activity. In the present study, we evaluated the in vitro metabolic stability (CL(int); mL/min/kg) of these compounds in human liver microsomes (HLMs), and assessed the relationship between their structures and CLint values. Among the compounds identified, N-{(3R)-1-[(6-fluoro-2-naphthyl) methyl] pyrrolidin-3-yl}-2-[ 1-(2-hydroxybenzoyl) piperidin-4-ylidene] acetamide (30j) was found to be a potent inhibitor (IC(50) = 8.4 nM) with a high metabolic stability against HLMs. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.06.066

文献信息

• Inhibition of chemokine CCL7 or receptor CCR3 of same for the treatment and diagnosis of prostate cancer
  申请人：Universite Paul Sabatier (Toulouse III)

  公开号：US10401365B2

  公开（公告）日：2019-09-03

  The invention concerns an inhibitor of the expression of chemokine CCL7 or an inhibitor of the expression of the receptor CCR3 or an inhibitor of CCL7/CCR3 interaction for the use of same to prevent or treat the extension of prostate cancer outside the prostatic capsule in a subject. The invention also concerns a method for determining the degree of aggressiveness of a prostate cancer tumor in a subject suffering from prostate cancer, comprising a step of determining the concentration or level of expression of the receptor CCR3 in a sample of prostate tumor cells obtained from said subject.

  本发明涉及一种趋化因子CCL7表达抑制剂或受体CCR3表达抑制剂或CCL7/CCR3相互作用抑制剂，用于预防或治疗受试者的前列腺癌向前列腺囊外延伸。本发明还涉及一种确定前列腺癌患者前列腺癌肿瘤侵袭程度的方法，该方法包括一个步骤，即确定从所述患者处获得的前列腺肿瘤细胞样本中受体CCR3的浓度或表达水平。
• Inhibition of Chemokine CCL7 or Receptor CCR3 of Same for the Treatment and Diagnosis of Prostate Cancer
  申请人：Universite Paul Sabatier (Toulouse III)

  公开号：US20170131282A1

  公开（公告）日：2017-05-11

  The invention concerns an inhibitor of the expression of chemokine CCL7 or an inhibitor of the expression of the receptor CCR3 or an inhibitor of CCL7/CCR3 interaction for the use of same to prevent or treat the extension of prostate cancer outside the prostatic capsule in a subject. The invention also concerns a method for determining the degree of aggressiveness of a prostate cancer tumour in a subject suffering from prostate cancer, comprising a step of determining the concentration or level of expression of the receptor CCR3 in a sample of prostate tumour cells obtained from said subject.
• Synthesis, biological evaluation, and metabolic stability of acrylamide derivatives as novel CCR3 antagonists
  作者：Ippei Sato、Koichiro Morihira、Hiroshi Inami、Hirokazu Kubota、Tatsuaki Morokata、Keiko Suzuki、Kazuki Ohno、Yosuke Iura、Aiko Nitta、Takayuki Imaoka、Toshiya Takahashi、Makoto Takeuchi、Mitsuaki Ohta、Shin-ichi Tsukamoto

  DOI：10.1016/j.bmc.2009.06.066

  日期：2009.8

  Our laboratory has identified several acrylamide derivatives with potent CCR3 inhibitory activity. In the present study, we evaluated the in vitro metabolic stability (CL(int); mL/min/kg) of these compounds in human liver microsomes (HLMs), and assessed the relationship between their structures and CLint values. Among the compounds identified, N-(3R)-1-[(6-fluoro-2-naphthyl) methyl] pyrrolidin-3-yl}-2-[ 1-(2-hydroxybenzoyl) piperidin-4-ylidene] acetamide (30j) was found to be a potent inhibitor (IC(50) = 8.4 nM) with a high metabolic stability against HLMs. (C) 2009 Elsevier Ltd. All rights reserved.