2-({[1-(4-bromo-2-isopropylphenyl)-5-(2,6-dimethoxyphenyl)-1H-pyrazol-3-yl]carbonyl}amino)adamantane-2-carboxylic acid | 1476064-46-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-({[1-(4-bromo-2-isopropylphenyl)-5-(2,6-dimethoxyphenyl)-1H-pyrazol-3-yl]carbonyl}amino)adamantane-2-carboxylic acid
• 英文别名: 2-({[1-(4-bromo-2-isopropylphenyl)-5-(2,6-dimethoxyphenyl)-1H-pyrazole-3-yl]carbonyl}amino)adamantane-2-carboxylic acid；2-[[1-(4-Bromo-2-propan-2-ylphenyl)-5-(2,6-dimethoxyphenyl)pyrazole-3-carbonyl]amino]adamantane-2-carboxylic acid；2-[[1-(4-bromo-2-propan-2-ylphenyl)-5-(2,6-dimethoxyphenyl)pyrazole-3-carbonyl]amino]adamantane-2-carboxylic acid
• CAS: 1476064-46-6
• 化学式: C₃₂H₃₆BrN₃O₅
• 分子量: 622.559
• InChiKey: RROBNHJDGIYYKM-UHFFFAOYSA-N

物化性质

• 沸点：
  731.4±60.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  41
• 可旋转键数：
  8
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-({[1-(4-bromo-2-isopropylphenyl)-5-(2,6-dimethoxyphenyl)-1H-pyrazol-3-yl]carbonyl}amino)adamantane-2-carboxylic acid 在 trans-di(μ-acetato)bis[o-(di-o-tolylphosphino)benzyl]dipalladium(II) 、 O-(N-succinimidyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 、 tri tert-butylphosphoniumtetrafluoroborate 作用下， 以 1,4-二氧六环 、 二甲基亚砜 为溶剂， 反应 0.5h， 生成 2,2',2''-(10-(2-((3-((3-(4-(3-((2-carboxyadamantan-2-yl)carbamoyl)-5-(2,6-dimethoxyphenyl)-1H-pyrazol-1-yl)-3-isopropyl-N-methylbenzamido)propyl)(methyl)amino)propyl)(methyl)amino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid
  参考文献：
  名称：

  10.1007/s00259-024-06754-2

  摘要：

  DOI：

  10.1007/s00259-024-06754-2
• 作为产物：
  描述：

  2-异丙基苯胺 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 ammonium acetate 、 水 、 三乙胺 、 potassium hydroxide 、 sodium nitrite 、 氯甲酸异丁酯 作用下， 以 1,4-二氧六环 、 水 、 乙腈 为溶剂， 反应 7.42h， 生成 2-({[1-(4-bromo-2-isopropylphenyl)-5-(2,6-dimethoxyphenyl)-1H-pyrazol-3-yl]carbonyl}amino)adamantane-2-carboxylic acid
  参考文献：
  名称：

  Efficient Synthesis of Heterocyclic Neurotensin Receptor Ligands by Microwave-Assisted Aminocarbonylation

  摘要：

  Marking the heterocyclic neurotensin receptor antagonist SR142948A as a lead compound, the development of an efficient and a practical synthetic route to heterocyclic aryl carboxamides is reported. Thus, a highly efficient and flexible access to these carboxamides was elaborated by taking advantage of microwave-assisted aminocarbonylation reaction mediated by Mo(CO)(6), Herrmann's palladacycle, [(t-Bu)(3)PH]BF4, and DBU.

  DOI：

  10.1055/s-0033-1338497

文献信息

• Development of Covalent Ligand–Receptor Pairs to Study the Binding Properties of Nonpeptidic Neurotensin Receptor 1 Antagonists
  作者：Ralf C. Kling、Manuel Plomer、Christopher Lang、Ashutosh Banerjee、Harald Hübner、Peter Gmeiner

  DOI：10.1021/acschembio.5b00965

  日期：2016.4.15

  receptor ligands requires molecular insights into the binding behavior of a particular lead compound. Although crystal structures of NTS1 have revealed the molecular determinants of peptide–agonist interactions, the binding mode of small-molecule antagonists remains largely unknown. Employing a disulfide-based tethering approach, we developed covalently binding molecular probes. The ligands 1 and 2

  已发现神经降压素受体NTS1具有药物相关性，因为它发现对多巴胺能信号转导具有调节作用，并参与肿瘤的进展。NTS1受体配体的合理药物设计需要分子洞察特定铅化合物的结合行为。尽管NTS1的晶体结构揭示了肽-激动剂相互作用的分子决定因素，但小分子拮抗剂的结合模式仍是未知之数。利用基于二硫键的束缚方法，我们开发了共价结合分子探针。配体1和2它们是基于非肽NTS1拮抗剂SR142948A的药效基团，允许与NTS1的工程化半胱氨酸残基形成二硫键。Cys127 2.65与配体之间的共价键位置用于通过分子动力学模拟预测共价拮抗剂1及其母体化合物SR142948A的结合模式。
• Synthesis and Evaluation of a ¹⁸F-Labeled Diarylpyrazole Glycoconjugate for the Imaging of NTS1-Positive Tumors
  作者：Christopher Lang、Simone Maschauer、Harald Hübner、Peter Gmeiner、Olaf Prante

  DOI：10.1021/jm401491e

  日期：2013.11.27

  Aiming to image NTS1 overexpressing tumors, the diarylpyrazole glycoconjugate 8, derived from the potent NTS1 antagonist SR142948A, was synthesized taking advantage of the palladium-catalyzed aminocarbonylation reaction. The glycoconjugate 8 displayed excellent affinity and selectivity toward NTS1. Radiosynthesis proceeded straightforwardly, obtaining [F-18]8 with excellent stability and highly beneficial biodistribution in vivo as demonstrated by PET imaging in HT29 tumor-bearing nude mice. Thus, the tracer [F-18]8 represents a highly promising candidate for PET imaging of NTS1-positive tumors.
• Efficient Synthesis of Heterocyclic Neurotensin Receptor Ligands by Microwave-Assisted Aminocarbonylation
  作者：Peter Gmeiner、Christopher Lang

  DOI：10.1055/s-0033-1338497

  日期：——

  Marking the heterocyclic neurotensin receptor antagonist SR142948A as a lead compound, the development of an efficient and a practical synthetic route to heterocyclic aryl carboxamides is reported. Thus, a highly efficient and flexible access to these carboxamides was elaborated by taking advantage of microwave-assisted aminocarbonylation reaction mediated by Mo(CO)(6), Herrmann's palladacycle, [(t-Bu)(3)PH]BF4, and DBU.
• 10.1007/s00259-024-06754-2
  作者：Zhang, Tao、Ma, Xinrui、Xu, Muyun、Cai, Jinghua、Cai, Jianhua、Cao, Yanguang、Zhang, Zhihao、Ji, Xin、He, Jian、Cabrera, German Oscar Fonseca、Wu, Xuedan、Zhao, Weiling、Wu, Zhanhong、Xie, Jin、Li, Zibo

  DOI：10.1007/s00259-024-06754-2

  日期：——