2-[(R)-1-ethyl-2-hydroxyethylamino]-9-isopropyl-6-[(pyridin-3-ylmethyl)-amino]purine

• 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-[(R)-1-ethyl-2-hydroxyethylamino]-9-isopropyl-6-[(pyridin-3-ylmethyl)-amino]purine
• 英文别名: (R)-2-(1-hydroxy-but-2-ylamino)-6-[(3-pyridyl)methylamino]-9-iso-propylpurine；(R)-2-(9-isopropyl-6-(pyridin-3-ylmethylamino)-9H-purin-2-ylamino)butan-1-ol；roscovitine；seliciclib；(2R)-2-[[9-propan-2-yl-6-(pyridin-3-ylmethylamino)purin-2-yl]amino]butan-1-ol
• 化学式: C₁₈H₂₅N₇O
• 分子量: 355.443
• InChiKey: ITWHOUBMQIJNKR-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  101
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2,6-二氯嘌呤 在 potassium carbonate 、 三乙胺 作用下， 以 二甲基亚砜 、 正丁醇 为溶剂， 反应 15.33h， 生成 2-[(R)-1-ethyl-2-hydroxyethylamino]-9-isopropyl-6-[(pyridin-3-ylmethyl)-amino]purine
  参考文献：
  名称：

  [EN] CALCIUM CHANNEL AGONISTS
  [FR] AGONISTES DE CANAUX CALCIQUES

  摘要：

  披露了钙通道激动剂的实施方式，以及制备和使用钙通道激动剂的方法。披露的钙通道激动剂及其相应的盐形式具有如下通用式I所示的结构，其中每个表示为“ ”的键是为了满足化合价要求而需要的单键或双键；Z1、Z2、Z3、Z4和Z5独立地是氮或碳；R1和R3是烷基；R2是烷基、芳基、杂环芳基、芳基烷基或杂环芳基烷基；而R4是烷基或羟基烷基。

  公开号：

  WO2014189830A1

文献信息

• [EN] CALCIUM CHANNEL AGONISTS<br/>[FR] AGONISTES DE CANAUX CALCIQUES
  申请人：UNIV PITTSBURGH

  公开号：WO2014189830A1

  公开（公告）日：2014-11-27

  Embodiments of calcium channel agonists, as well as methods of making and using the calcium channel agonists, are disclosed. The disclosed calcium channel agonists and corresponding salt forms have a structure according to general formula I wherein each bond depicted as " " is a single bond or a double bond as needed to satisfy valence requirements; Z1, Z2, Z3, Z4, and Z5 independently are nitrogen or carbon; R1 and R3 are alkyl; R2 is alkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl; and R4 is alkyl or hydroxyalkyl.

  披露了钙通道激动剂的实施方式，以及制备和使用钙通道激动剂的方法。披露的钙通道激动剂及其相应的盐形式具有如下通用式I所示的结构，其中每个表示为“ ”的键是为了满足化合价要求而需要的单键或双键；Z1、Z2、Z3、Z4和Z5独立地是氮或碳；R1和R3是烷基；R2是烷基、芳基、杂环芳基、芳基烷基或杂环芳基烷基；而R4是烷基或羟基烷基。
• CALCIUM CHANNEL AGONISTS
  申请人：WIPF Peter

  公开号：US20160090387A1

  公开（公告）日：2016-03-31

  Embodiments of calcium channel agonists, as well as methods of making and using the calcium channel agonists, are disclosed. The disclosed calcium channel agonists and corresponding salt forms have a structure according to general formula I: wherein each bond depicted as “ ” is a single bond or a double bond as needed to satisfy valence requirements; Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 independently are nitrogen or carbon; R 1 and R 3 are alkyl; R 2 is alkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl; and R 4 is alkyl or hydroxyalkyl.

  本发明揭示了钙通道激动剂的实施方式，以及制备和使用钙通道激动剂的方法。所述的钙通道激动剂和相应的盐形式具有通式I的结构：其中，每个表示为“”的键是单键或双键，以满足价键要求；Z1、Z2、Z3、Z4和Z5独立地为氮或碳；R1和R3为烷基；R2为烷基、芳基、杂芳基、芳基烷基或杂芳基烷基；R4为烷基或羟基烷基。
• Calcium channel agonists
  申请人：University of Pittsburgh—Of the Commonwealth System of Higher Education

  公开号：US10174031B2

  公开（公告）日：2019-01-08

  Embodiments of calcium channel agonists, as well as methods of making and using the calcium channel agonists, are disclosed. The disclosed calcium channel agonists and corresponding salt forms have a structure according to general formula I: wherein each bond depicted as “” is a single bond or a double bond as needed to satisfy valence requirements; Z1, Z2, Z3, Z4, and Z5 independently are nitrogen or carbon; R1 and R3 are alkyl; R2 is alkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl; and R4 is alkyl or hydroxyalkyl.

  本发明公开了钙通道激动剂的实施方案以及钙通道激动剂的制造和使用方法。所公开的钙通道激动剂和相应的盐形式具有通式 I 的结构： 其中描述为""的每个键是单键或双键，以满足化合价要求；Z1、Z2、Z3、Z4 和 Z5 独立地为氮或碳；R1 和 R3 为烷基；R2 为烷基、芳基、杂芳基、芳烷基或杂芳基烷基；R4 为烷基或羟烷基。
• Design, synthesis and biological evaluation of 6-pyridylmethylaminopurines as CDK inhibitors
  作者：Stuart C. Wilson、Butrus Atrash、Clare Barlow、Susan Eccles、Peter M. Fischer、Angela Hayes、Lloyd Kelland、Wayne Jackson、Michael Jarman、Amin Mirza、Javier Moreno、Bernard P. Nutley、Florence I. Raynaud、Peter Sheldrake、Mike Walton、Robert Westwood、Steven Whittaker、Paul Workman、Edward McDonald

  DOI：10.1016/j.bmc.2011.08.051

  日期：2011.11

  The cyclin-dependent kinase (CDK) inhibitor seliciclib (1, CYC202) is in phase II clinical development for the treatment of cancer. Here we describe the synthesis of novel purines with greater solubility, lower metabolic clearance, and enhanced potency versus CDKs. These compounds exhibit novel selectivity profiles versus CDK isoforms. Compound alpha SbR-21 inhibits CDK2/cyclin E with IC(50) = 30 nM, CDK7-cyclin H with IC(50) = 1.3 mu M, and CDK9-cyclinT with IC(50) = 0.11 mu M; it (CCT68127) inhibits growth of HCT116 colon cancer cells in vitro with GI(50) = 0.7 mu M; and shows antitumour activity when dosed p.o. at 50 mg/kg to mice bearing HCT116 solid human tumour xenografts. (C) 2011 Elsevier Ltd. All rights reserved.
• Roscovitine-Derived, Dual-Specificity Inhibitors of Cyclin-Dependent Kinases and Casein Kinases 1
  作者：Nassima Oumata、Karima Bettayeb、Yoan Ferandin、Luc Demange、Angela Lopez-Giral、Marie-Lorène Goddard、Vassilios Myrianthopoulos、Emmanuel Mikros、Marc Flajolet、Paul Greengard、Laurent Meijer、Hervé Galons

  DOI：10.1021/jm800109e

  日期：2008.9.11

  Cyclin-dependent kinases (CDKs) and casein kinases 1 (CK 1) are involved in the two key molecular features of Alzheimer's disease, production of amyloid-beta peptides (extracellular plaques) and hyper-phosphorylation of Tau (intracellular neurofibrillary tangles). A series of 2,6,9-trisubstituted purines, structurally related to the CDK inhibitor roscovitine, have been synthesized. They mainly differ by the substituent on the C-6 position. These compounds were screened for kinase inhibitory activities and antiproliferative effects. Several biaryl derivatives displayed potent inhibition of both CDKs and CK1. In particular, derivative 13a was a potent inhibitor of CDK1/cyclin B (IC50: 220 nM), CDK5/p25 (IC50: 80 nM), and CK1 (IC50: 14 nM). Modeling of these molecules into the ATP-binding pocket of CK1 delta provided a rationale for the increased selectivity toward this kinase. 13a was able to prevent the CK1-dependent production of anyloid-beta in a cell model. CDK/CK1 dual-specificity inhibitors may have important applications in Alzheimer's disease and cancers.