4-[6-(8-cyclopentyl-6-iodo-5-methyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino)pyridin-3-yl]piperazine-1-carboxylic acid tert-butyl ester | 571189-22-5

• 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-[6-(8-cyclopentyl-6-iodo-5-methyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino)pyridin-3-yl]piperazine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 4-(6-(8-cyclopentyl-6-iodo-5-methyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino)pyridin-3-yl)piperazine-1-carboxylate；Tert-butyl 4-(6-(8-cyclopentyl-7,8-dihydro-6-iodo-5-methyl-7-oxopyrido[2,3-d]pyrimidin-2-ylamino)pyridin-3-yl)piperazine-1-carboxylate；tert-butyl 4-[6-[(8-cyclopentyl-6-iodo-5-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]pyridin-3-yl]piperazine-1-carboxylate
• CAS: 571189-22-5
• 化学式: C₂₇H₃₄IN₇O₃
• 分子量: 631.517
• InChiKey: LNMGSWWUNLOLFY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  38
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-[6-(8-cyclopentyl-6-iodo-5-methyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino)pyridin-3-yl]piperazine-1-carboxylic acid tert-butyl ester 在 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 2.0h， 以95%的产率得到8-cyclopentyl-6-iodo-5-methyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one
  参考文献：
  名称：

  Radiosynthesis and radiopharmacological evaluation of cyclin-dependent kinase 4 (Cdk4) inhibitors

  摘要：

  Tumor cells are characterized by their loss of growth control resulting from alterations in regulating pathways of the cell cycle, such as a deregulated cyclin-dependent kinase (Cdk) activity and/or Cdk expression. Appropriately radiolabeled Cdk4 inhibitors are discussed as promising molecular probes for imaging cell proliferation processes and tumor visualization by PET. This work describes the design, synthesis and radiopharmacological evaluation of two I-124-labeled Cdk4 inhibitors as potential radio-tracers for imaging of Cdk4 in vivo. Treatment of a solution containing labeling precursors with [I-124]NaI gave radiolabeled Cdk4 inhibitors [I-124]CKIA and [I-124]CKIB in radiochemical yields of up to 35%. I-124- labeled radiotracers [I-124]CKIA and [I-124]CKIB were used in cell uptake studies as well as biodistribution studies in Wistar rats and small-animal PET in tumor-bearing mice. In vitro radiotracer uptake studies in adherent tumor cells using [I-124]CKIA showed substantial uptake in HT-29 and FaDu cells (750-850% ID/mg protein [I-124]CKIA and 900-1000 %ID/mg protein [I-124]CKIB) after 1 h at 37 degrees C. Biodistribution of [I-124]CKIA and [I-124]CKIB showed rapid blood clearance of radioactivity and an accumulation as well as metabolization in the liver. Both radiotracers were administered intravenously to mouse FaDu xenograft tumor model and imaging studies were performed on a small-animal PET scanner. Both imaging techniques showed only little uptake of both radiotracers in the FaDu tumor xenografts. (C) 2009 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2009.11.020
• 作为产物：
  描述：

  2-chloro-N-cyclopentylpyrimidin-4-amine 在 potassium tert-butylate 、 三氯化硼 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-[6-(8-cyclopentyl-6-iodo-5-methyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino)pyridin-3-yl]piperazine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  帕博西尼新合成方法

  摘要：

  本发明提供一种帕博西尼的新合成方法，包括如下步骤：1)在碱和溶剂的作用下，将中间体V和中间体B1进行缩合反应得到化合物VI；2)化合物VI与格氏试剂交换后与酰化试剂反应得到化合物VII,当X为乙酰基时，化合物VI即为化合物VII；3)化合物VII在羟乙基磺酸作用下脱保护反应再成盐得到成品帕博西尼X。该合成方法工艺路线简单、成本低廉、适宜工业化生产。合成路线为：

  公开号：

  CN106565707B

文献信息

• 2-(Pyridin-2-ylamino)-pyrido[2,3-d]pyrimidin-7-ones
  申请人：——

  公开号：US20030149001A1

  公开（公告）日：2003-08-07

  The present invention provides substituted 2-aminopyridines useful in treating cell proliferative disorders. The novel compounds of the present invention are potent inhibitors of cyclin-dependent kinases 4 (cdk4). 1

  这项发明提供了用于治疗细胞增殖性疾病的取代2-氨基吡啶。本发明的新化合物是cyclin-dependent激酶4 (cdk4)的有效抑制剂。
• [EN] 2-(PYRIDIN-2-YLAMINO)-PYRIDO[2,3d]PYRIMIDIN-7-ONES<br/>[FR] 2-(PYRIDIN-2-YLAMINO)-PYRIDO[2,3-D]PYRIMIDIN-7-ONES
  申请人：WARNER LAMBERT CO

  公开号：WO2003062236A1

  公开（公告）日：2003-07-31

  The present invention provides substituted 2-aminopyridines useful in treating cell proliferative disorders. The novel compounds of the present invention are potent inhibitors of cyclin-dependent kinases 4 ( cdk4 ).

  本发明提供了用于治疗细胞增殖性疾病的取代的2-氨基吡啶。本发明的新化合物是cyclin-dependent kinases 4 (cdk4)的有效抑制剂。
• 2-(Pyridin-2-ylamino)-pyrido [2,3-D]pyrimidin-7-ones
  申请人：Barvian Mark

  公开号：US20050137214A1

  公开（公告）日：2005-06-23

  The present invention provides substituted 2-aminopyridines useful in treating cell proliferative disorders. The novel compounds of the present invention are potent inhibitors of cyclin-dependent kinases 4 (cdk4).

  本发明提供了可用于治疗细胞增殖性疾病的取代的2-氨基吡啶。本发明的新型化合物是cyclin-dependent kinases 4 (cdk4)的强效抑制剂。
• 2-(PYRIDIN-2-YLAMINO)-PYRIDO [2,3 D]PYRIMIDIN-7-ONES
  申请人：Barvian Mark

  公开号：US20070179118A1

  公开（公告）日：2007-08-02

  The present invention provides substituted 2-aminopyridines useful in treating cell proliferative disorders. The novel compounds of the present invention are potent inhibitors of cyclin-dependent kinases 4 (cdk4).

  本发明提供了替代2-氨基吡啶，用于治疗细胞增殖性疾病。本发明的新化合物是cyclin-dependent kinases 4 (cdk4)的有效抑制剂。
• 2-(PYRIDIN-2-YLAMINO)-PYRIDO 2,3-d]PYRIMIDIN-7-ONES
  申请人：Warner-Lambert Company LLC

  公开号：EP1470124B1

  公开（公告）日：2005-12-28