2-(tert-butylthio)-5-chloro-6-[(2R)-4-(2-hydroxyethyl)-2-methylpiperazin-1-yl]-1H-benzimidazole | 1042106-65-9

• 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: 2-(tert-butylthio)-5-chloro-6-[(2R)-4-(2-hydroxyethyl)-2-methylpiperazin-1-yl]-1H-benzimidazole
• 英文别名: Benzimidazole-based antagonist, 1；2-[(3R)-4-(2-tert-butylsulfanyl-6-chloro-1H-benzimidazol-5-yl)-3-methylpiperazin-1-yl]ethanol
• CAS: 1042106-65-9
• 化学式: C₁₈H₂₇ClN₄OS
• 分子量: 382.958
• InChiKey: PRUISXHHETXRED-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  80.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (R)-5-(4-(2-((tert-butyldimethylsilyl)oxy)ethyl)-2-methylpiperazin-1-yl)-6-chloro-1,3-dihydro-2H-benzo[d]imidazole-2-thione 、 叔丁醇 在 三氟乙酸 作用下， 反应 16.0h， 以78%的产率得到2-(tert-butylthio)-5-chloro-6-[(2R)-4-(2-hydroxyethyl)-2-methylpiperazin-1-yl]-1H-benzimidazole
  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

• ACTIVE SUBSTANCE AND PHARMACEUTICAL COMPOSITION FOR TREATING ALCOHOL DEPENDENCE, AND A METHOD FOR OBTAINING AND THE USE OF SAID ACTIVE SUBSTANCE
  申请人：Ivashchenko Andrey Alexandrovich

  公开号：US20110245231A1

  公开（公告）日：2011-10-06

  The invention relates to novel drug substance for the treatment of alcohol dependence, pharmaceutical composition, medicament and method for treatment of dependence on using ethyl alcohol containing beverages. The invention provides a drug substance for treating alcohol dependence in human and warm-blooded animals representing substituted 1H-benzimidazoles of the general formula 1 or pharmaceutically acceptable salts and/or hydrates thereof wherein: W represents S or S═0 group; R 1 represents one or more substituent selected from hydrogen, halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, optionally substituted azaheterocyclyl; R 2 represents hydrogen or optionally substituted C 1 -C 4 alkyl; R 3 and R 4 independently represent optionally identical substituents selected from hydrogen or optionally substituted C 1 -C 4 alkyl; R 5 represents an alkyl substituent selected from hydrogen, optionally substituted C 1 -C 7 alkyl, optionally substituted aryl, optionally substituted heterocyclyl, C 1 -C 4 alkoxycarbonyl, optionally substituted aminocarbonyl.
• Novel ORL1-selective antagonists with oral bioavailability and brain penetrability
  作者：Osamu Okamoto、Kensuke Kobayashi、Hiroshi Kawamoto、Satoru Ito、Takashi Yoshizumi、Izumi Yamamoto、Masaya Hashimoto、Atsushi Shimizu、Hiroyuki Takahashi、Yasuyuki Ishii、Satoshi Ozaki、Hisashi Ohta

  DOI：10.1016/j.bmcl.2008.04.037

  日期：2008.6

  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.