1-(2-(1-(tert-butoxycarbonyl)piperidin-4-yl)ethyl)-4-nitro-1H-pyrazole-3-carboxylic acid | 1215184-25-0

• 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: 1-(2-(1-(tert-butoxycarbonyl)piperidin-4-yl)ethyl)-4-nitro-1H-pyrazole-3-carboxylic acid
• CAS: 1215184-25-0
• 化学式: C₁₆H₂₄N₄O₆
• 分子量: 368.39
• InChiKey: KWNHWRQGFFNWDJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.53
• 重原子数：
  26.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  127.8
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  1-(2-(1-(tert-butoxycarbonyl)piperidin-4-yl)ethyl)-4-nitro-1H-pyrazole-3-carboxylic acid 在 palladium on activated charcoal 、 氢气 、 二异丁基氢化铝 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 16.0h， 生成 (R)-tert-butyl 4-(2-(6-benzyl-4-heptanoyl-8-oxo-5,6,7,8-tetrahydropyrazolo[4,3-e][1,4]diazepin-2(4H)-yl)ethyl)piperidine-1-carboxylate
  参考文献：
  名称：

  Discovery and structure–activity relationships of pyrazolodiazepine derivatives as the first small molecule agonists of the Drosophila sex peptide receptor

  摘要：

  In behavioral research, the sex peptide receptor in Drosophila melanogaster (DrmSPR) is the most interesting G protein-coupled receptor (GPCR) and is involved in post-mating responses such as increased egg-laying and decreased receptivity of the female; during these responses, the receptors are activated by a specific natural peptide agonist (sex peptide, SP). To discover small molecule agonists for DrmSPR, a compound library based on a pyrazolodiazepine scaffold, which was previously reported as a potential privileged structure, was screened. Structure-activity relationship (SAR) studies of the hit compounds, which exhibited weak agonistic effects (69-72% activation at 100 mu M), were explored through the synthesis of various analogs with substituents at the R-1, R-2, R-3 and R-4 positions of the pyrazolodiazepine skeleton. As a result, compounds 21 and 31 of the 6-benzyl pyrazolodiazepine derivative series were found to be small molecule agonists for DrmSPR with EC50 values of 3-4 mu M. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.02.035
• 作为产物：
  描述：

  tert-butyl 4-(2-(3-(methoxycarbonyl)-4-nitro-1H-pyrazol-1-yl)ethyl)piperidine-1-carboxylate 在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 1.0h， 生成 1-(2-(1-(tert-butoxycarbonyl)piperidin-4-yl)ethyl)-4-nitro-1H-pyrazole-3-carboxylic acid
  参考文献：
  名称：

  Discovery and structure–activity relationships of pyrazolodiazepine derivatives as the first small molecule agonists of the Drosophila sex peptide receptor

  摘要：

  In behavioral research, the sex peptide receptor in Drosophila melanogaster (DrmSPR) is the most interesting G protein-coupled receptor (GPCR) and is involved in post-mating responses such as increased egg-laying and decreased receptivity of the female; during these responses, the receptors are activated by a specific natural peptide agonist (sex peptide, SP). To discover small molecule agonists for DrmSPR, a compound library based on a pyrazolodiazepine scaffold, which was previously reported as a potential privileged structure, was screened. Structure-activity relationship (SAR) studies of the hit compounds, which exhibited weak agonistic effects (69-72% activation at 100 mu M), were explored through the synthesis of various analogs with substituents at the R-1, R-2, R-3 and R-4 positions of the pyrazolodiazepine skeleton. As a result, compounds 21 and 31 of the 6-benzyl pyrazolodiazepine derivative series were found to be small molecule agonists for DrmSPR with EC50 values of 3-4 mu M. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.02.035

文献信息

• Synthesis and structure–activity relationships of pyrazolodiazepine derivatives as human P2X7 receptor antagonists
  作者：Ju-Yeon Lee、Juan Yu、Won Je Cho、Hyojin Ko、Yong-Chul Kim

  DOI：10.1016/j.bmcl.2009.09.053

  日期：2009.11

  Screening of library compounds has yielded pyrazolodiazepine derivatives with P2X(7) receptor antagonist activity. To explore the structure -activity relationships (SAR) of these pyrazolodiazepines as human P2X(7) receptor antagonists, derivatives were synthesized by substitutions at positions R-2 and R-3 of the pyrazolodiazepine skeleton. Using a 2'(3')-O-(4-benzoylbenzoyl)ATP (BzATP)-induced fluorescent ethidium uptake assay, the activities of these derivatives were tested in HEK-293 cells stably expressing human P2X(7) receptors. Moreover, the effect of these derivatives was assessed by measuring their effect on IL-1 beta release induced by BzATP-induced activation of differentiated THP-1 cells. A 2-phenethyl pyrazolodiazepine derivative with a 1-methyl-1H-3-indolyl group at position R-2 had fivefold greater activity than the derivative with a 5-isoquinolinyl at R-2. Moreover, a benzyl moiety at R-3 had fivefold greater activity than a bicyclic moiety. The stereochemical effect at C-6 showed a preference for the (R)-isomer. Among the series of active derivatives, compound 23b, with a phenethyl group at R-1, a 3-methyl indole at R-2, and a benzyl at R-3, exhibited activity similar to that of the positive control, KN-62, as shown by the inhibitory effects of IL-1 beta release. (C) 2009 Elsevier Ltd. All rights reserved.