4-(5-amino-4-phenylsulfonyl-1H-pyrazol-3-yl)piperazine-1-carboxylic acid tert-butyl ester | 1173163-63-7

• 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-(5-amino-4-phenylsulfonyl-1H-pyrazol-3-yl)piperazine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 4-[5-amino-4-(benzenesulfonyl)-1H-pyrazol-3-yl]piperazine-1-carboxylate
• CAS: 1173163-63-7
• 化学式: C₁₈H₂₅N₅O₄S
• 分子量: 407.494
• InChiKey: YPVCFQRMKLRMOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  130
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(5-amino-4-phenylsulfonyl-1H-pyrazol-3-yl)piperazine-1-carboxylic acid tert-butyl ester 在 乙醇 、 溶剂黄146 、 乙酰氯 作用下， 以 氯仿 为溶剂， 反应 4.0h， 生成 5,7-dimethyl-3-(phenylsulfonyl)-2-piperazin-1-ylpyrazolo[1,5-a]pyrimidine hydrochloride
  参考文献：
  名称：

  2-Substituted 5,6-dimethyl-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidines: New series of highly potent and specific serotonin 5-HT6 receptor antagonists

  摘要：

  Syntheses, biological evaluation, and structure activity relationships for a series of novel 2-substituted 3-benzenesulfonyl-5,6-dimethyl-pyrazolo[1,5-a]pyrimidines are disclosed. In spite of a wide, four orders of magnitude, SAR range (K-i varied from 260 pM to 2.96 mu M), no significant correlation of 5-HT6R antagonistic potency was observed with major physiochemical characteristics, such as molecular weight, surface polar area, cLogP, or number of rotatable bonds. Statistically significant trend was only observed for size of substitute group, which was not enough to explain the deep SAR trend. Besides with the substitute group size, another factor that presumably plays a role in defining the compound potencies is a relative position of the heterocycle and sulfophenyl moieties. Among all synthesized derivatives, (3-benzenesulfonyl-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methyl-amine 18 is the most potent (K-i = 260 pM) and extremely selective, 5000 to >50,000-fold relative to 55 therapeutic targets, antagonist of the 5-HT6 receptor. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.01.038
• 作为产物：
  描述：

  2-苯磺酰基-3,3-二(甲硫基)丙烯腈 在 一水合肼 作用下， 以 异丙醇 为溶剂， 反应 0.5h， 生成 4-(5-amino-4-phenylsulfonyl-1H-pyrazol-3-yl)piperazine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  2-Substituted 5,6-dimethyl-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidines: New series of highly potent and specific serotonin 5-HT6 receptor antagonists

  摘要：

  Syntheses, biological evaluation, and structure activity relationships for a series of novel 2-substituted 3-benzenesulfonyl-5,6-dimethyl-pyrazolo[1,5-a]pyrimidines are disclosed. In spite of a wide, four orders of magnitude, SAR range (K-i varied from 260 pM to 2.96 mu M), no significant correlation of 5-HT6R antagonistic potency was observed with major physiochemical characteristics, such as molecular weight, surface polar area, cLogP, or number of rotatable bonds. Statistically significant trend was only observed for size of substitute group, which was not enough to explain the deep SAR trend. Besides with the substitute group size, another factor that presumably plays a role in defining the compound potencies is a relative position of the heterocycle and sulfophenyl moieties. Among all synthesized derivatives, (3-benzenesulfonyl-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methyl-amine 18 is the most potent (K-i = 260 pM) and extremely selective, 5000 to >50,000-fold relative to 55 therapeutic targets, antagonist of the 5-HT6 receptor. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.01.038

文献信息

• (3-Phenylsulfonylcycloalkano[<i>e</i> and <i>d</i>]pyrazolo[1,5-<i>a</i>]pyrimidin-2-yl)amines: Potent and Selective Antagonists of the Serotonin 5-HT₆ Receptor
  作者：Alexandre V. Ivachtchenko、Dmitri E. Dmitriev、Elena S. Golovina、Madina G. Kadieva、Angela G. Koryakova、Volodymyr M. Kysil、Oleg D. Mitkin、Ilya M. Okun、Sergey E. Tkachenko、Anton A. Vorobiev

  DOI：10.1021/jm100350r

  日期：2010.7.22

  5-HT6 receptors are exclusively localized in the CNS and have high affinity with many psychotropic agents. Though the role of this receptor in many CNS diseases is widely anticipated, lack of definite progress in the development of 5-HT6 receptor-oriented drugs indicates a need for further discoveries of novel chemotypes with high potency and high selectivity to the receptor. Here we present preparations and biological evaluation of a series of (3-phenylsulfonylcycloalkano[e and d]pyrazolo[1,5-a]pyrimidin-2-yl)amines. Phenylsulfonylcyclopentapyrazolopyrimidine 7 was found to be a highly selective 5-HT6 receptor antagonist with high affinity (low picomolar range) and potency. 7 and a few of its analogues were further tested for biological effect on 5-HT2B receptors and hERG potassium channels, potential liability targets. Such liability appears to be minimal, based on the in vitro data.
• 2-Substituted 5,6-dimethyl-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidines: New series of highly potent and specific serotonin 5-HT6 receptor antagonists
  作者：Alexandre V. Ivachtchenko、Elena S. Golovina、Madina G. Kadieva、Angela G. Koryakova、Oleg D. Mitkin、Sergey E. Tkachenko、Volodymyr M. Kysil、Ilya Okun

  DOI：10.1016/j.ejmech.2011.01.038

  日期：2011.4

  Syntheses, biological evaluation, and structure activity relationships for a series of novel 2-substituted 3-benzenesulfonyl-5,6-dimethyl-pyrazolo[1,5-a]pyrimidines are disclosed. In spite of a wide, four orders of magnitude, SAR range (K-i varied from 260 pM to 2.96 mu M), no significant correlation of 5-HT6R antagonistic potency was observed with major physiochemical characteristics, such as molecular weight, surface polar area, cLogP, or number of rotatable bonds. Statistically significant trend was only observed for size of substitute group, which was not enough to explain the deep SAR trend. Besides with the substitute group size, another factor that presumably plays a role in defining the compound potencies is a relative position of the heterocycle and sulfophenyl moieties. Among all synthesized derivatives, (3-benzenesulfonyl-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methyl-amine 18 is the most potent (K-i = 260 pM) and extremely selective, 5000 to >50,000-fold relative to 55 therapeutic targets, antagonist of the 5-HT6 receptor. (C) 2011 Elsevier Masson SAS. All rights reserved.