tert butyl-4-(1,8-naphthyridine-2-carbonyl)piperazine-1-carboxylate | 1395398-66-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: tert butyl-4-(1,8-naphthyridine-2-carbonyl)piperazine-1-carboxylate
• CAS: 1395398-66-9
• 化学式: C₁₈H₂₂N₄O₃
• 分子量: 342.398
• InChiKey: XDWADLSPXMKOGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.32
• 重原子数：
  25.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  75.63
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  tert butyl-4-(1,8-naphthyridine-2-carbonyl)piperazine-1-carboxylate 在 potassium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 32.0h， 生成 (4-(4-bromobenzyl)piperazin-1-yl)(1,8-naphthyridin-2-yl)methanone
  参考文献：
  名称：

  Synthesis and in Vivo Evaluation of [¹²³I]Melanin-Targeted Agents

  摘要：

  study reports the synthesis, [I-123]radiolabeling, and biological profile of a new series of iodinated compounds for potential translation to the corresponding [I-131]radiolabeled compounds for radionuclide therapy of melanoma. Radiolabeling was achieved via standard electrophilic iododestannylation in 60-90% radiochemical yield. Preliminary SPECT imaging demonstrated high and distinct tumor uptake of all compounds, as well as high tumor-to-background ratios compared to the literature compound [I-123]4 (ICF01012). The most favorable compounds ([I-123]20, [I-123]23, [I-123] 41, and [I-123]53) were selected for further biological investigation. Biodistribution studies indicated that all four compounds bound to melanin containing tissue with low in vivo deiodination; [I-123]20 and [I-123]53 in particular displayed high and prolonged tumor uptake (13% ID/g at 48 h). [I-123]53 had the most favorable overall profile of the cumulative uptake over time of radiosensitive organs. Metabolite analysis of the four radiotracers found [I-123]41 and [I-123]53 to be the most favorable, displaying high and prolonged amounts of intact tracer in melanin containing tissues, suggesting melanin specific binding. Results herein suggest that compound [I-123]53 displays favorable in vivo pharrnacokinetics and stability and hence is an ideal candidate to proceed with further preclinical [I-131] therapeutic evaluation.

  DOI：

  10.1021/acs.jmedchem.5b00777
• 作为产物：
  描述：

  2-氨基-3-吡啶甲醛 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 tert butyl-4-(1,8-naphthyridine-2-carbonyl)piperazine-1-carboxylate
  参考文献：
  名称：

  Synthesis and in Vivo Evaluation of [¹²³I]Melanin-Targeted Agents

  摘要：

  study reports the synthesis, [I-123]radiolabeling, and biological profile of a new series of iodinated compounds for potential translation to the corresponding [I-131]radiolabeled compounds for radionuclide therapy of melanoma. Radiolabeling was achieved via standard electrophilic iododestannylation in 60-90% radiochemical yield. Preliminary SPECT imaging demonstrated high and distinct tumor uptake of all compounds, as well as high tumor-to-background ratios compared to the literature compound [I-123]4 (ICF01012). The most favorable compounds ([I-123]20, [I-123]23, [I-123] 41, and [I-123]53) were selected for further biological investigation. Biodistribution studies indicated that all four compounds bound to melanin containing tissue with low in vivo deiodination; [I-123]20 and [I-123]53 in particular displayed high and prolonged tumor uptake (13% ID/g at 48 h). [I-123]53 had the most favorable overall profile of the cumulative uptake over time of radiosensitive organs. Metabolite analysis of the four radiotracers found [I-123]41 and [I-123]53 to be the most favorable, displaying high and prolonged amounts of intact tracer in melanin containing tissues, suggesting melanin specific binding. Results herein suggest that compound [I-123]53 displays favorable in vivo pharrnacokinetics and stability and hence is an ideal candidate to proceed with further preclinical [I-131] therapeutic evaluation.

  DOI：

  10.1021/acs.jmedchem.5b00777

文献信息

• Dipeptidyl peptidase-4 inhibitor with β-amino amide scaffold: Synthesis, SAR and biological evaluation
  作者：Heung Jae Kim、Woo Young Kwak、Jong Pil Min、Si Young Sung、Ha Dong Kim、Mi Kyung Kim、Hae Sun Kim、Kyung Jin Park、Moon Ho Son、Soon Hoe Kim、Bong Jin Lee

  DOI：10.1016/j.bmcl.2012.07.019

  日期：2012.9

  Inhibitors of dipeptidyl peptidase-4 (DPP4) have been shown to be effective treatments for type 2 diabetes. Several series of beta-amino amide containing piperazine derivatives have been prepared and evaluated as a inhibitor of DPP4. Finally compound 5m was selected for further evaluation. (C) 2012 Elsevier Ltd. All rights reserved.