{4-[4-(2-isopropoxy-phenyl)-piperazin-1-yl]-cyclohexyl}-carbamic acid tert-butyl ester | 886206-08-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: {4-[4-(2-isopropoxy-phenyl)-piperazin-1-yl]-cyclohexyl}-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[4-[4-(2-propan-2-yloxyphenyl)piperazin-1-yl]cyclohexyl]carbamate
• CAS: 886206-08-2
• 化学式: C₂₄H₃₉N₃O₃
• 分子量: 417.592
• InChiKey: IJGVIZAGYFTYRC-UHFFFAOYSA-N

物化性质

• 沸点：
  542.8±50.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  54
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  {4-[4-(2-isopropoxy-phenyl)-piperazin-1-yl]-cyclohexyl}-carbamic acid tert-butyl ester 在 sodium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 生成
  参考文献：
  名称：

  (Arylpiperazinyl)cyclohexylsufonamides: Discovery of α1a/1d-selective adrenergic receptor antagonists for the treatment of Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms (BPH/LUTS)

  摘要：

  Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms (BPH/LUTS) can be effectively treated by alpha(1)-adrenergic receptor antagonists. Unfortunately, all currently marketed alpha(1), blockers produced CV related side effects that are caused by the subtype non-selective nature of the drugs. To overcome this problem, it was postulated that a alpha(1a/1d) subtype selective antagonist would bring more benefit for the treatment of BPH/LUTS. In developing selective alpha(1a/1d) ligands, (arylpiperazinyl)cyclohexylsulfonamides were synthesized and their binding profiles against three cloned human alpha(1)-adrenergic receptor subtypes were evaluated. Many compounds show equal affinity for both alpha(1a), and alpha(1d) subtypes with good selectivity against the alpha(1b) subtype. They also overcome the problem of dopamine receptor affinity that previous analogues had exhibited. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.04.008
• 作为产物：
  描述：

  4-N-Boc-氨基环己酮 在 三乙酰氧基硼氢化钠 、 溶剂黄146 、 水 、 氯化铵 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以96%的产率得到{4-[4-(2-isopropoxy-phenyl)-piperazin-1-yl]-cyclohexyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  WO2007/1818

  摘要：

  公开号：

文献信息

• Substituted [4-(4-phenyl-piperazin-1-yl)-cyclohexyl]-urea compounds
  申请人：Chiu George

  公开号：US20070123542A1

  公开（公告）日：2007-05-31

  The present invention relates to substituted [4-(4-phenyl-piperazin-1-yl)-cyclohexyl]-urea 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 methods of treatment.

  本发明涉及一种替代[4-(4-苯基哌嗪-1-基)-环己基]-脲化合物(I)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增生和下尿路症状。本发明还涉及包含所述新化合物的制药组合物、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。
• WO2006/50048
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.
• WO2007/5214
  申请人：——

  公开号：——

  公开（公告）日：——
• 1-Arylpiperazinyl-4-cyclohexylamine derived isoindole-1,3-diones as potent and selective α-1a/1d adrenergic receptor ligands
  作者：Shengjian Li、George Chiu、Virginia L. Pulito、Jingchun Liu、Peter J. Connolly、Steven A. Middleton

  DOI：10.1016/j.bmcl.2006.12.111

  日期：2007.3

  Subtype-selective alpha-la and/or alpha-1d adrenergic receptor antagonists may be useful for the treatment of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) with fewer adverse effects than non-selective drugs. A series of 1-aryl-piperazinyl-4-cyclohexylamine derived isoindole-1,3-diones has been synthesized, displaying in vitro alpha(1a) and aid binding affinity K-i values in the range of 0.09-38 nM with K-i(alpha(1b))/K-i(alpha(1a)) and K-i(alpha(1b))/K-i(alpha(1d)) selectivity ratios up to 3607-fold. (c) 2007 Elsevier Ltd. All rights reserved.