4-(4-(2-(2-fluoroethoxy)phenyl)piperidin-1-yl)cyclohexan-1-amine | 946605-82-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-(4-(2-(2-fluoroethoxy)phenyl)piperidin-1-yl)cyclohexan-1-amine
• CAS: 946605-82-9
• 化学式: C₁₉H₂₉FN₂O
• 分子量: 320.45
• InChiKey: ZADJPRMFTPIWAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.48
• 重原子数：
  23.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  38.49
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  4-(4-(2-(2-fluoroethoxy)phenyl)piperidin-1-yl)cyclohexan-1-amine 、 3,4-二甲氧基苯磺酰氯 在 sodium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 生成 N-cis-(4-{4-[2-(2-fluoro-ethoxy)-phenyl]-piperidin-1-yl}-cyclohexyl)-3,4-dimethoxy-benzenesulfonamide 、 N-trans-(4-{4-[2-(2-fluoro-ethoxy)-phenyl]-piperidin-1-yl}-cyclohexyl)-3,4-dimethoxy-benzenesulfonamide
  参考文献：
  名称：

  (Phenylpiperidinyl)cyclohexylsulfonamides: Development of α1a/1d-selective adrenergic receptor antagonists for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS)

  摘要：

  Although alpha(1), adrenergic receptor blockers can be very effective for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS), their usage is limited by CV-related side-effects that are caused by the subtype non-selective nature of the current drugs. To overcome this problem, it was hypothesized that a alpha(1a/1d) subtype selective antagonist would bring more benefit for the therapy of BPH/LUTS. In developing such selective alpha(1a/1d) ligands, a series of (phenylpiperidinyl)cyclohexylsulfonamides has been synthesized and evaluated for binding to three cloned human alpha(1)-adrenergic receptor subtypes. Many compounds showed equal affinity for both alpha(1a) and alpha(1d) subtypes with good selectivity versus the alpha(1b) subtype. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.04.098
• 作为产物：
  描述：

  1-溴-2-(2-氟乙氧基)苯 在 palladium on activated charcoal 正丁基锂 、 氢气 、 三乙酰氧基硼氢化钠 、 溶剂黄146 、 甲基磺酰氯 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， -78.0~20.0 ℃ 、310.27 kPa 条件下， 反应 36.0h， 生成 4-(4-(2-(2-fluoroethoxy)phenyl)piperidin-1-yl)cyclohexan-1-amine
  参考文献：
  名称：

  (Phenylpiperidinyl)cyclohexylsulfonamides: Development of α1a/1d-selective adrenergic receptor antagonists for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS)

  摘要：

  Although alpha(1), adrenergic receptor blockers can be very effective for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS), their usage is limited by CV-related side-effects that are caused by the subtype non-selective nature of the current drugs. To overcome this problem, it was hypothesized that a alpha(1a/1d) subtype selective antagonist would bring more benefit for the therapy of BPH/LUTS. In developing such selective alpha(1a/1d) ligands, a series of (phenylpiperidinyl)cyclohexylsulfonamides has been synthesized and evaluated for binding to three cloned human alpha(1)-adrenergic receptor subtypes. Many compounds showed equal affinity for both alpha(1a) and alpha(1d) subtypes with good selectivity versus the alpha(1b) subtype. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.04.098

文献信息

• Aminocyclohexylsulfonamides: Discovery of metabolically stable α1a/1d-selective adrenergic receptor antagonists for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS)
  作者：George Chiu、Shengjian Li、Hong Cai、Peter J. Connolly、Sean Peng、Kathe Stauber、Virginia Pulito、Jingchun Liu、Steven A. Middleton

  DOI：10.1016/j.bmcl.2007.09.051

  日期：2007.11

  Benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS) can be effectively treated by a, adrenergic receptor antagonists, but these drugs also produce side effects that are related to their subtype non-selective nature. To overcome this limitation, it was hypothesized that an alpha(1a/1d) subtype-selective antagonist would be efficacious while keeping side effects to a minimum. To discover alpha(1a/1d)-selective antagonists and improve metabolic stability of our previously reported compounds, we have designed and synthesized a series of (phenylpiperazinyl)- or (phenylpiperidinyl)-cyclohexylsulfonamides. By incorporating the information obtained from metabolism studies, we were able to discover several compounds that are both alpha(1a/1d) adrenoceptor subtype selective and show increased stability toward human liver microsomal metabolism. The selectivity profile of these compounds provides great improvement over the commercial drug tamsulosin, hence may pave the way to the development of new and efficacious therapeutic agents with reduced side effects. (C) 2007 Elsevier Ltd. All rights reserved.