6-benzylamino-2-[(1R,2RS)-1-ethyl-2-hydroxy-3-methylbutylamino]-9-isopropylpurine | 482615-16-7

• 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: 6-benzylamino-2-[(1R,2RS)-1-ethyl-2-hydroxy-3-methylbutylamino]-9-isopropylpurine
• 英文别名: (4R)-4-[[6-(benzylamino)-9-propan-2-ylpurin-2-yl]amino]-2-methylhexan-3-ol
• CAS: 482615-16-7
• 化学式: C₂₂H₃₂N₆O
• 分子量: 396.536
• InChiKey: CCMLBTWPLDKEBS-DUSLRRAJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  87.9
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-氟-6-氯嘌呤 在 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 2,4-滴二甲胺盐 、 二甲基亚砜 、 正丁醇 为溶剂， 反应 139.5h， 生成 6-benzylamino-2-[(1R,2RS)-1-ethyl-2-hydroxy-3-methylbutylamino]-9-isopropylpurine
  参考文献：
  名称：

  Design, synthesis and biological evaluation of 6-pyridylmethylaminopurines as CDK inhibitors

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2011.08.051

文献信息

• 2,6,9-Substituted purine derivatives and their use in the treatment of proliferative disorders
  申请人：Fischer Martin Peter

  公开号：US20050009846A1

  公开（公告）日：2005-01-13

  The present invention relates to compounds of formula I or a pharmaceutically acceptable salt thereof wherein R 2 is 2-hydroxymethylpyrrolidin- 1 -yl, or NHCH(R 4 )CH(R 3 )OH, wherein R 3 is hydrogen or methyl and R 4 is methyl, ethyl or isopropyl; R 6 is 3-nitrophenylamino, 3,4-dimethoxybenzylamino, 3-iodobenzyl-amino, pyrid-2-yl-methylamino, pyrid-4-yl-methylamino or indan-5-amino; R 9 is isopropyl or cyclopentanyl. In a further aspect, the invention relates to pharmaceutical compositions comprising said compounds, and the use thereof in treating antiproliferative disorders and or viral disorders.

  本发明涉及式I的化合物或其药学上可接受的盐，其中R2为2-羟甲基吡咯烷-1-基或NHCH（R4）CH（R3）OH，其中R3为氢或甲基，R4为甲基、乙基或异丙基；R6为3-硝基苯胺基、3,4-二甲氧基苯甲基氨基、3-碘苯甲基氨基、吡啶-2-基甲基氨基、吡啶-4-基甲基氨基或茚-5-基氨基；R9为异丙基或环戊基。在进一步方面，本发明涉及包括所述化合物的制药组合物及其在治疗抗增殖性疾病和/或病毒性疾病中的用途。
• 2,6,9-SUBSTITUTED PURINE DERIVATIVES AND THEIR USE IN THE TREATMENT OF PROLIFERATIVE DISORDERS
  申请人：Cyclacel Limited

  公开号：EP1399446B1

  公开（公告）日：2005-08-03
• US7612079B2
  申请人：——

  公开号：US7612079B2

  公开（公告）日：2009-11-03
• [EN] PROCESS<br/>[FR] PROCÉDÉ
  申请人：CYCLACEL LTD

  公开号：WO2007110649A2

  公开（公告）日：2007-10-04

  [EN] The present invention relates to a process for preparing a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R² is (a) where R³, R⁴, R⁷ and R⁸ are each independently selected from H, alkyl, aryl and aralkyl, said alkyl, aryl and aralkyl groups each being optionally substituted with one or more R¹² groups, and wherein at least one of R³, R⁴, R⁷ and R⁸ is other than H; R⁵ is OH, O-alkyl, NH₂, H, alkyl, aryl or aralkyl, said alkyl, aryl and aralkyl groups each being optionally substituted with one or more R¹² groups; R⁶ is NR¹⁰R¹¹, wherein R¹⁰ and R¹¹ are each independently H or hydrocarbyl; R⁹ is hydrocarbyl; and each R¹² is independently selected from OR¹³, halo, alkyl, COOR¹⁴, CONR¹⁵R¹⁶, SO₂NR¹⁷R¹⁸, NO₂, CN, NR¹⁹R²⁰SR²¹ and CF₃, where R^13-21 are each independently H, alkyl or aryl; said process comprising the steps of (II) (III) (IV) (i) converting a compound of formula (II) to a compound of formula (III), wherein X is halo and R is aryl, alkyl, cycloalkyl, aralkyl, heteroaryl or alkyl-heteroaryl; (ii) converting said compound of formula (III) to a compound of formula (IV); and (iii) converting said compound of formula (IV) to a compound of formula (I).
  [FR] La présente invention concerne un procédé de fabrication d'un composé de formule (I) ou d'un de ses sels pharmaceutiquement acceptables, dans laquelle R² représente (a) et R³, R⁴, R⁷ et R⁸ sont chacun choisis indépendamment parmi H, alkyle, aryle et aralkyle, lesdits groupements alkyle, aryle et aralkyle étant chacun éventuellement substitués par un ou plusieurs groupements R¹² et au moins un des substituants R³, R⁴, R⁷ et R⁸ n'étant pas H ; R⁵ représente OH, O-alkyle, NH₂, H, alkyle, aryle ou aralkyle, lesdits groupements alkyle, aryle et aralkyle étant chacun éventuellement substitués par un ou plusieurs groupements R¹² ; R⁶ représente NR¹⁰R¹¹, R¹⁰ et R¹¹ représentant indépendamment H ou hydrocarbyle ; R⁹ représente hydrocarbyle ; et chaque R¹² est indépendamment choisi parmi OR¹³, halogéno, alkyle, COOR¹⁴, CONR¹⁵R¹⁶, SO₂NR¹⁷R¹⁸, NO₂, CN, NR¹⁹R²⁰SR²¹ et CF₃, R^13-21 représentant indépendamment H, alkyle ou aryle ; ledit procédé comprenant les étapes suivantes (II) (III) (IV) (i) convertir un composé de formule (II) en un composé de formule (III), dans lequel X représente halogéno et R représente aryle, alkyle, cycloalkyle, aralkyle, hétéroaryle ou alkyl-hétéroaryle ; (ii) convertir ledit composé de formule (III) en un composé de formule (IV) ; et (iii) convertir ledit composé de formule (IV) en un composé de formule (I).
• 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.