1-[(6-fluoro-2-naphthyl)methyl]-1,4-diazepane | 406923-88-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-[(6-fluoro-2-naphthyl)methyl]-1,4-diazepane
• 英文别名: 1-[(6-fluoronaphthalen-2-yl)methyl]-1,4-diazepane
• CAS: 406923-88-4
• 化学式: C₁₆H₁₉FN₂
• 分子量: 258.339
• InChiKey: UJGFKSAHLCAQEL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.77
• 重原子数：
  19.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  15.27
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  1-[(6-fluoro-2-naphthyl)methyl]-1,4-diazepane 、 二氢-3-(异十二碳烯基)呋喃-2,5-二酮 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 盐酸 作用下， 以 N,N-二甲基甲酰胺 、 乙酸乙酯 为溶剂， 以26%的产率得到1-(biphenyl-2-ylcarbonyl)-4-[(6-fluoro-2-naphthyl)-methyl]-1,4-diazepane hydrochloride
  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
• 作为产物：
  描述：

  高哌嗪 、 2-bromomethyl-6-fluoronaphthalene 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 20.0h， 以77%的产率得到1-[(6-fluoro-2-naphthyl)methyl]-1,4-diazepane
  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

• Pyrrolidinyl phenylurea derivatives as novel CCR3 antagonists
  作者：Aiko Nitta、Yosuke Iura、Hideki Inoue、Ippei Sato、Koichiro Morihira、Hirokazu Kubota、Tatsuaki Morokata、Makoto Takeuchi、Mitsuaki Ohta、Shin-ichi Tsukamoto、Takayuki Imaoka、Toshiya Takahashi

  DOI：10.1016/j.bmcl.2012.09.035

  日期：2012.11

  Optimization starting with our lead compound 1 (IC50 = 4.9 nM) led to the identification of pyrrolidinyl phenylurea derivatives. Further modification toward improvement of the bioavailability provided (R)-1-(1-((6-fluoronaphthalen-2-yl)methyl)pyrrolidin-3-yl)-3-(2-(2-hydroxyethoxy)phenyl)urea 32 (IC50 = 1.7 nM), a potent and orally active CCR3 antagonist. (C) 2012 Elsevier Ltd. All rights reserved.