NU2017 | 220028-09-1

• 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: NU2017
• 英文别名: 6-Cyclohexylmethoxypurine；6-(cyclohexylmethoxy)-7H-purine
• CAS: 220028-09-1
• 化学式: C₁₂H₁₆N₄O
• 分子量: 232.285
• InChiKey: ZJSUFVUNHNCHCI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  63.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (RS)-3-methoxy-2,3-dihydro-5H-1,4-benzodioxepin 、 NU2017 在 四氯化锡 、 六甲基二硅氮烷 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 以21%的产率得到6-(cyclohexylmethoxy)-7-(3,5-dihydro-2H-1,4-benzodioxepin-3-yl)purine
  参考文献：
  名称：

  Regiospecific microwave-assisted synthesis and cytotoxic activity against human breast cancer cells of (RS)-6-substituted-7- or 9-(2,3-dihydro-5H-1,4-benzodioxepin-3-yl)-7H- or -9H-purines

  摘要：

  Extended studies on the synthesis and pharmacological evaluation of (RS)-6-substituted-7 or 9-(2,3-dihydro-5H-1,4-benzodioxepin-3-yl)-7H- or -9H-purines are presented. The microwave-assisted organic synthesis has provided faster access to the target compounds with the advantage of selective obtaining the N-7 ' or N-9 ' regioisomers simplifying their isolation. To test the behaviour of the products (including the purine bases) on cellular systems, cytotoxic activity against the MCF-7 human breast cancer cell line was determined, and the three most active compounds were used to study the cell cycle distribution and apoptosis in the MCF-7 cell line. (c) 2007 Elsevier Masson SAS. All fights reserved.

  DOI：

  10.1016/j.ejmech.2007.10.025
• 作为产物：
  描述：

  6-氯嘌呤 、 环己甲醇 在 sodium 作用下， 以 水 为溶剂， 以70%的产率得到NU2017
  参考文献：
  名称：

  Cyclin dependent kinase inhibiting purine derivatives

  摘要：

  治疗肿瘤或其他细胞增殖紊乱的方法包括给予有效剂量的嘌呤化合物，其抑制循环依赖性激酶活性。还公开了新型嘌呤化合物和制药组合物。

  公开号：

  US06303618B1

文献信息

• Identification of Novel Purine and Pyrimidine Cyclin-Dependent Kinase Inhibitors with Distinct Molecular Interactions and Tumor Cell Growth Inhibition Profiles
  作者：Christine E. Arris、F. Thomas Boyle、A. Hilary Calvert、Nicola J. Curtin、Jane A. Endicott、Elspeth F. Garman、Ashleigh E. Gibson、Bernard T. Golding、Sharon Grant、Roger J. Griffin、Philip Jewsbury、Louise N. Johnson、Alison M. Lawrie、David R. Newell、Martin E. M. Noble、Edward A. Sausville、Robert Schultz、Wyatt Yu

  DOI：10.1021/jm990628o

  日期：2000.7.1

  Substituted guanines and pyrimidines were tested as inhibitors of cyclin B1/CDK1 and cyclin A3/CDK2 and soaked into crystals of monomeric CDK2. O-6-Cyclohexylmethylguanine (NU2058) was a competitive inhibitor of CDK1 and CDK2 with respect to ATP (Ki values: CDK1, 5 +/-: 1 mu M; CDK2, 12 +/- 3 mu M) and formed a triplet of hydrogen bonds (i.e., NH-9 to Glu 81, N-3 to Leu 83, and 2-NH2 to Leu 83). The triplet of hydrogen bonding and CDK inhibition was reproduced by 2,6-diamino-4-cyclohexylmethyloxy-5-nitrosopyrimidine (NU6027, K-i values: CDK1, 2.5 +/- 0.4 mu M; CDK2, 1.3 +/- 0.2 mu M). Against human tumor cells, NU2058 and NU6027 were growth inhibitory in vitro (mean GI(50) values of 13 +/- 7 mu M and 10 +/- 6 mu M, respectively), with a pattern of sensitivity distinct from flavopiridol and olomoucine. These CDK inhibition and chemosensitivity data indicate that the distinct mode of binding of NU2058 and NU6027 has direct consequences for enzyme and cell growth inhibition.
• CYCLIN DEPENDENT KINASE INHIBITING PURINE DERIVATIVES
  申请人：Cancer Research Technology Limited

  公开号：EP1017394B1

  公开（公告）日：2005-12-07
• US6303618B1
  申请人：——

  公开号：US6303618B1

  公开（公告）日：2001-10-16
• US7826979B2
  申请人：——

  公开号：US7826979B2

  公开（公告）日：2010-11-02
• [EN] CYCLIN DEPENDENT KINASE INHIBITING PURINE DERIVATIVES<br/>[FR] DERIVES DE PURINE INHIBANT LA KINASE DEPENDANT DE LA CYCLINE
  申请人：——

  公开号：WO1999002162A1

  公开（公告）日：1999-01-21

  [EN] A range is disclosed of purine derivatives (I) which can act as inhibitors of cyclin dependent kinases (CDKs) and which thereby c an provide useful therapeutic compounds for use in treatment of tumours or other cell proliferation disorders. The compounds of this invention bind to CDK molecules in a manner that appears to be different to that of known CDK inhibitors such as olomoucine and roscovitine. In formula (I), in preferred embodiments: X is O, S or CHRx where Rx is H or C1-4 alkyl; D is H, halo or NZ1Z2 where Z1 and Z2 are each independently H or C1-4 alkyl or C1-4 hydroxyalkyl; A is selected from H, C1-4 alkyl, C1-4 alkoxy, hydroxy, CH2(CH2)nOH (n=1-4), and NRa1Ra2 where Ra1 and Ra2 are each independently H or C1-4 alkyl; B is selected from H, C1-4 alkyl, C1-4 alkoxy, CF3, an optionally substituted aryl (e.g. phenyl) or an optionally substituted aralkyl (e.g. benzyl), and an hydroxy group that provides a C=O tautomer; and Y is or includes an optionally substituted 4- to 8-membered carbocyclic or heterocyclic ring; or comprises an optionally substituted linear or branched hydrocarbon chain.
  [FR] L'invention porte sur une gamme de dérivés de purine (I) pouvant agir comme inhibiteurs des kinases dépendant de la cycline (CDK) et pouvant, par conséquent, produire des composés thérapeutiques destinés à être utilisés dans le traitement de tumeurs ou autres troubles de la prolifération cellulaire. Ces composés se lient à des molécules de CDK de façon à être différents de ceux produits par des inhibiteurs connus de CDK tels que olomoucine et roscovitine. Dans la formule (I), selon des réalisations préférées, X représente O, S ou CHRx, Rx représentant H ou alkyle C1-4; D représente H, halo ou NZ1Z2, Z1 et Z2 représentant chacun, indépendamment H, ou alkyle C1-4 ou hydroxyalkyle C1-4; A est sélectionné parmi H, alkyle C1-4, alcoxy C1-4, hydroxy, Ch2(CH2)nOH (n=1-4), et NRa1Ra2, Ra1 et Ra2 représentant chacun, indépendamment, H ou alkyle C1-4; B est sélectionné parmi H, alkyle C1-4, alcoxy C1-4, CF3, un aryle éventuellement substitué (tel que phényle) ou un aralkyle éventuellement substitué (tel que benzyle), et un groupe hydroxy qui produit un tautomère C=O; et Y représente ou comprend un noyau carbocyclique ou hétérocyclique à 4 ou 8 éléments; ou une chaîne d'hydrocarbure linéaire ou ramifiée, éventuellement substituée.