tert-butyl (R)-4-(5-amino-2-chloro-4-nitrophenyl)-3-methylpiperazine-1-carboxylate | 1042106-70-6

• 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: tert-butyl (R)-4-(5-amino-2-chloro-4-nitrophenyl)-3-methylpiperazine-1-carboxylate
• CAS: 1042106-70-6
• 化学式: C₁₆H₂₃ClN₄O₄
• 分子量: 370.836
• InChiKey: NAKFKLIKYGXYEU-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.28
• 重原子数：
  25.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  101.94
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (R)-4-(5-amino-2-chloro-4-nitrophenyl)-3-methylpiperazine-1-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  Novel ORL1-selective antagonists with oral bioavailability and brain penetrability

  摘要：

  Following the discovery of 5-chloro-6-[piperazin-1-yl]-1H-benzimidazole as a novel pharmacophore for potent and selective ORL1 antagonist activity, optimization of this new lead by introduction of a methyl substitution on the piperazine ring resulted in a highly potent and selective, orally available, and brain penetrable ORL1 antagonist, 2-(tert-butylthio)-5-chloro-6-[(2R)-4-(2-hydroxyethyl)-2-methylpiperazin-1-yl]-1 H-benzimidazole. Stereochemistry of the methyl substituent on the piperazine ring to control the functional activity of other opioid receptors is also described. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.04.037
• 作为产物：
  描述：

  4-氯-5-氟-2-硝基苯胺 、 (R)-4-Boc-2-甲基哌嗪 在 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 18.0h， 以52%的产率得到tert-butyl (R)-4-(5-amino-2-chloro-4-nitrophenyl)-3-methylpiperazine-1-carboxylate
  参考文献：
  名称：

  Novel ORL1-selective antagonists with oral bioavailability and brain penetrability

  摘要：

  Following the discovery of 5-chloro-6-[piperazin-1-yl]-1H-benzimidazole as a novel pharmacophore for potent and selective ORL1 antagonist activity, optimization of this new lead by introduction of a methyl substitution on the piperazine ring resulted in a highly potent and selective, orally available, and brain penetrable ORL1 antagonist, 2-(tert-butylthio)-5-chloro-6-[(2R)-4-(2-hydroxyethyl)-2-methylpiperazin-1-yl]-1 H-benzimidazole. Stereochemistry of the methyl substituent on the piperazine ring to control the functional activity of other opioid receptors is also described. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.04.037

文献信息

• Optimization of benzimidazole series as opioid receptor-like 1 (ORL1) antagonists: SAR study directed toward improvement of selectivity over hERG activity
  作者：Kensuke Kobayashi、Tetsuya Kato、Izumi Yamamoto、Atsushi Shimizu、Sayaka Mizutani、Masanori Asai、Hiroshi Kawamoto、Satoru Ito、Takashi Yoshizumi、Mioko Hirayama、Satoshi Ozaki、Hisashi Ohta、Osamu Okamoto

  DOI：10.1016/j.bmcl.2009.04.022

  日期：2009.6

  A structure-activity relationship (SAR) study on the benzimidazole series of opioid receptor-like 1 (ORL1) antagonists related to 1 is described. Optimization of 1 by introduction of a hydrophilic substituent into the thioether part resulted in identification of potent ORL1 antagonists with high selectivity over binding affinity for hERG and other opioid receptors. (C) 2009 Elsevier Ltd. All rights reserved.