1-cycloheptyl-6-(methylsulfonyl)-1H-pyrazolo[3,4-d]pyrimidine | 1206679-21-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 1-cycloheptyl-6-(methylsulfonyl)-1H-pyrazolo[3,4-d]pyrimidine
• 英文别名: 1-cycloheptyl-6-methylsulfonylpyrazolo[3,4-d]pyrimidine
• CAS: 1206679-21-1
• 化学式: C₁₃H₁₈N₄O₂S
• 分子量: 294.378
• InChiKey: ORFMDXVMTDTWBR-UHFFFAOYSA-N

物化性质

• 沸点：
  510.6±42.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  86.1
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  1-cycloheptyl-6-(methylsulfonyl)-1H-pyrazolo[3,4-d]pyrimidine 在 potassium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 氯仿 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-(5-(1-cycloheptyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino)pyridin-2-yl)-N-(2-morpholinoethyl)methanesulfonamide
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of pyrazolopyrimidine-sulfonamides as potent multiple-mitotic kinase (MMK) inhibitors (part I)

  摘要：

  A novel class of pyrazolopyrimidine-sulfonamides was discovered as selective dual inhibitors of aurora kinase A (AKA) and cyclin-dependent kinase 1 (CDK1). These inhibitors were originally designed based on an early lead (compound I). SAR development has led to the discovery of potent inhibitors with single digit nM IC(50)s towards both AKA and CDK1. An exemplary compound 1a has demonstrated good efficacy in an HCT116 colon cancer xenograft model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.129
• 作为产物：
  描述：

  6-(甲基硫代)-1H-吡唑并[3,4-d]嘧啶 在 Oxone 、 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成 1-cycloheptyl-6-(methylsulfonyl)-1H-pyrazolo[3,4-d]pyrimidine
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of pyrazolopyrimidine-sulfonamides as potent multiple-mitotic kinase (MMK) inhibitors (part I)

  摘要：

  A novel class of pyrazolopyrimidine-sulfonamides was discovered as selective dual inhibitors of aurora kinase A (AKA) and cyclin-dependent kinase 1 (CDK1). These inhibitors were originally designed based on an early lead (compound I). SAR development has led to the discovery of potent inhibitors with single digit nM IC(50)s towards both AKA and CDK1. An exemplary compound 1a has demonstrated good efficacy in an HCT116 colon cancer xenograft model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.129

文献信息

• Design, synthesis, and biological evaluation of pyrazolopyrimidine-sulfonamides as potent multiple-mitotic kinase (MMK) inhibitors (part I)
  作者：Lin Zhang、Junhua Fan、Jer-Hong Chong、Angela Cesena、Betty Y.Y. Tam、Charles Gilson、Christina Boykin、Deping Wang、Dikran Aivazian、Doug Marcotte、Guangqing Xiao、Jean-Yves Le Brazidec、Jinhua Piao、Karen Lundgren、Kevin Hong、Khang Vu、Khanh Nguyen、Liang-Shang Gan、Laura Silvian、Leona Ling、Min Teng、Mitchell Reff、Nicole Takeda、Noel Timple、Qin Wang、Ron Morena、Samina Khan、Shuo Zhao、Tony Li、Wen-Cherng Lee、Arthur G. Taveras、Jianhua Chao

  DOI：10.1016/j.bmcl.2011.06.129

  日期：2011.9

  A novel class of pyrazolopyrimidine-sulfonamides was discovered as selective dual inhibitors of aurora kinase A (AKA) and cyclin-dependent kinase 1 (CDK1). These inhibitors were originally designed based on an early lead (compound I). SAR development has led to the discovery of potent inhibitors with single digit nM IC(50)s towards both AKA and CDK1. An exemplary compound 1a has demonstrated good efficacy in an HCT116 colon cancer xenograft model. (C) 2011 Elsevier Ltd. All rights reserved.
• Synthesis, SAR and biological evaluation of 1,6-disubstituted-1H-pyrazolo[3,4-d]pyrimidines as dual inhibitors of Aurora kinases and CDK1
  作者：Jean-Yves Le Brazidec、Angela Pasis、Betty Tam、Christina Boykin、Cheryl Black、Deping Wang、Gisela Claassen、Jer-Hong Chong、Jianhua Chao、Junhua Fan、Khanh Nguyen、Laura Silvian、Leona Ling、Lin Zhang、Michael Choi、Min Teng、Nuzhat Pathan、Shuo Zhao、Tony Li、Art Taveras

  DOI：10.1016/j.bmcl.2012.01.019

  日期：2012.3

  Since the early 2000s, the Aurora kinases have become major targets of oncology drug discovery particularly Aurora-A and Aurora-B kinases (AKA/AKB) for which the selective inhibition in cells lead to different phenotypes. In addition to targeting these Aurora kinases involved in mitosis, CDK1 has been added as a primary inhibition target in hopes of enhancing the cytotoxicity of our chemotypes harboring the pyrazolopyrimidine core. SAR optimization of this series using the AKA, AKB and CDK1 biochemical assays led to the discovery of the compound 7h which combines strong potency against the 3 kinases with an acceptable microsomal stability. Finally, switching from a primary amide to a two-substituted pyrrolidine amide gave rise to compound 15a which exhibited the desired AKA/CDK1 inhibition phenotype in cells but showed moderate activity in animal models using HCT116 tumor cell lines. (C) 2012 Elsevier Ltd. All rights reserved.