4-[4-(2-cyclopropoxy-phenyl)-piperidin-1-yl]-cyclohexylamine | 946605-74-9

• 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-cyclopropoxy-phenyl)-piperidin-1-yl]-cyclohexylamine
• 英文别名: 4-[2-(2,2,2-Trifluoroethoxy)phenyl]piperidine
• CAS: 946605-74-9
• 化学式: C₁₃H₁₆F₃NO
• 分子量: 259.271
• InChiKey: UMJNMDZXQAEOPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[4-(2-cyclopropoxy-phenyl)-piperidin-1-yl]-cyclohexylamine 在 三乙酰氧基硼氢化钠 、 sodium carbonate 、 溶剂黄146 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 20.0h， 生成 3,4-dimethoxy-N-cis-(4-{4-[2-(2,2,2-trifluoro-ethoxy)-phenyl]-piperidin-1-yl}-cyclohexyl)-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：

  4-[2-(2,2,2-trifluoro-ethoxy)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以100%的产率得到4-[4-(2-cyclopropoxy-phenyl)-piperidin-1-yl]-cyclohexylamine
  参考文献：
  名称：

  Piperidinyl substituted cyclohexane-1,4-diamines

  摘要：

  本发明涉及式(I)的哌啶取代的环己烷-1,4-二胺化合物及其药学上可接受的形式，作为α1a/α1d肾上腺素受体调节剂，用于治疗良性前列腺肥大和下尿路症状。本发明还涉及包含所述新化合物的药物组合物，制备这些新化合物的新方法以及作为药物的新用途和治疗方法。

  公开号：

  US20060217419A1

文献信息

• Piperidinyl substituted cyclohexane-1,4-diamines
  申请人：Chiu George

  公开号：US20060217419A1

  公开（公告）日：2006-09-28

  The present invention relates to piperidine substituted cyclohexane-1,4-diamine compounds of Formula (I) and pharmaceutically acceptable forms thereof, as α 1a /α 1d adrenoreceptor modulators for the treatment of benign prostatic hypertrophy and lower urinary tract symptoms. The present invention also relates to pharmaceutical compositions comprising said new compounds, new processes to prepare these new compounds and new uses as a medicine as well as method of treatments.

  本发明涉及式(I)的哌啶取代的环己烷-1,4-二胺化合物及其药学上可接受的形式，作为α1a/α1d肾上腺素受体调节剂，用于治疗良性前列腺肥大和下尿路症状。本发明还涉及包含所述新化合物的药物组合物，制备这些新化合物的新方法以及作为药物的新用途和治疗方法。
• 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.
• US7470711B2
  申请人：——

  公开号：US7470711B2

  公开（公告）日：2008-12-30
• (Phenylpiperidinyl)cyclohexylsulfonamides: Development of 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、Peter J. Connolly、Virginia Pulito、Jingchun Liu、Steven A. Middleton

  DOI：10.1016/j.bmcl.2007.04.098

  日期：2007.7

  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.