2-chloro-4-(2-fluoro-9-isopropyl-9H-purin-6-ylamino)benzoic acid | 231951-16-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 2-chloro-4-(2-fluoro-9-isopropyl-9H-purin-6-ylamino)benzoic acid
• 英文别名: 2-Chloro-4-[(2-fluoro-9-propan-2-ylpurin-6-yl)amino]benzoic acid
• CAS: 231951-16-9
• 化学式: C₁₅H₁₃ClFN₅O₂
• 分子量: 349.752
• InChiKey: FQQKLZRYVBJKBY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  92.9
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-chloro-4-(2-fluoro-9-isopropyl-9H-purin-6-ylamino)benzoic acid 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 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 反应 96.0h， 生成 WMY-1-103
  参考文献：
  名称：

  Fluorescent cyclin-dependent kinase inhibitors block the proliferation of human breast cancer cells

  摘要：

  Inhibitors of cyclin-dependent kinases (CDKs) are an emerging class of drugs for the treatment of cancers. CDK inhibitors are currently under evaluation in clinical trials as single agents and as sensitizers in combination with radiation therapy and chemotherapies. Drugs that target CDKs could have important inhibitory effects on cancer cell cycle progression, an extremely important mechanism in the control of cancer cell growth. Using rational drug design, we designed and synthesized fluorescent CDK inhibitors (VMY-1-101 and VMY-1-103) based on a purvalanol B scaffold. The new agents demonstrated more potent CDK inhibitory activity, enhanced induction of G2/M arrest and modest apoptosis as compared to purvalanol B. Intracellular imaging of the CDK inhibitor distribution was performed to reveal drug retention in the cytoplasm of treated breast cancer cells. In human breast cancer tissue, the compounds demonstrated increased binding as compared to the fluorophore. The new fluorescent CDK inhibitors showed undiminished activity in multidrug resistance (MDR) positive breast cancer cells, indicating that they are not a substrate for p-glycoprotein. Fluorescent CDK inhibitors offer potential as novel theranostic agents, combining therapeutic and diagnostic properties in the same molecule. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.02.052
• 作为产物：
  描述：

  6-chloro-2-fluoro-9-isopropyl-9H-purine 、 4-氨基-2-氯苯甲酸 在 N,N-二异丙基乙胺 作用下， 以 正丁醇 为溶剂， 反应 12.0h， 以100%的产率得到2-chloro-4-(2-fluoro-9-isopropyl-9H-purin-6-ylamino)benzoic acid
  参考文献：
  名称：

  Fluorescent cyclin-dependent kinase inhibitors block the proliferation of human breast cancer cells

  摘要：

  Inhibitors of cyclin-dependent kinases (CDKs) are an emerging class of drugs for the treatment of cancers. CDK inhibitors are currently under evaluation in clinical trials as single agents and as sensitizers in combination with radiation therapy and chemotherapies. Drugs that target CDKs could have important inhibitory effects on cancer cell cycle progression, an extremely important mechanism in the control of cancer cell growth. Using rational drug design, we designed and synthesized fluorescent CDK inhibitors (VMY-1-101 and VMY-1-103) based on a purvalanol B scaffold. The new agents demonstrated more potent CDK inhibitory activity, enhanced induction of G2/M arrest and modest apoptosis as compared to purvalanol B. Intracellular imaging of the CDK inhibitor distribution was performed to reveal drug retention in the cytoplasm of treated breast cancer cells. In human breast cancer tissue, the compounds demonstrated increased binding as compared to the fluorophore. The new fluorescent CDK inhibitors showed undiminished activity in multidrug resistance (MDR) positive breast cancer cells, indicating that they are not a substrate for p-glycoprotein. Fluorescent CDK inhibitors offer potential as novel theranostic agents, combining therapeutic and diagnostic properties in the same molecule. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.02.052

文献信息

• FLUORESCENT CDK INHIBITORS FOR TREATMENT OF CANCER
  申请人：Yenugonda Venkata Mahidhar

  公开号：US20110269178A1

  公开（公告）日：2011-11-03

  Disclosed are molecules and their synthesis. The fluorescent moiety also facilitates screening, tracking, and pharmacodynamic studies of the drug in a biological system both in vitro and in vivo.

  本发明涉及一些分子及其合成方法。荧光部分还可以促进药物在体外和体内生物系统中的筛选、追踪和药效学研究。
• US9408848B2
  申请人：——

  公开号：US9408848B2

  公开（公告）日：2016-08-09
• [EN] FLUORESCENT CDK INHIBITORS FOR TREATMENT OF CANCER<br/>[FR] INHIBITEURS DE CDK FLUORESCENTS POUR LE TRAITEMENT DU CANCER
  申请人：UNIV GEORGETOWN

  公开号：WO2010019967A1

  公开（公告）日：2010-02-18

  Disclosed are molecules and their synthesis,. The fluorescent moiety also facilitates screening, tracking, and pharmacodynamic studies of the drug in a biological system both in vitro and in vivo.