[(1S,2R)-2-(6-aminopurin-9-yl)cyclopentyl]methanol | 182265-76-5

• 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: [(1S,2R)-2-(6-aminopurin-9-yl)cyclopentyl]methanol
• CAS: 182265-76-5
• 化学式: C₁₁H₁₅N₅O
• 分子量: 233.273
• InChiKey: SKHQGPMILDEHMB-HTQZYQBOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  89.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [(1S,2R)-2-(6-aminopurin-9-yl)cyclopentyl]methanol 在 三正丁胺 、 Dowex-50W X-8 cation-exchange resin in the pyridinium form 、 三丁基焦磷酸铵 、 N,N'-羰基二咪唑 、 三氯氧磷 作用下， 生成 (1R,2S)-1-(6-aminopurin-9-yl)-2-(hydroxymethyl)cyclopentane triphosphate
  参考文献：
  名称：

  化学酶法合成的新型对映体纯净的碳环核苷类似物，对末端脱氧核苷酸转移酶具有强抑制作用。

  摘要：

  描述了基于反式-2-（羟甲基）环戊醇衍生物的动力学拆分制备的对映体纯的碳环腺苷衍生物的合成。他们相应的三磷酸盐被评估为人类免疫缺陷病毒的DNA聚合酶β，末端脱氧核苷酸转移酶（TdT），端粒酶，大肠杆菌DNA聚合酶I和逆转录酶的抑制剂。令人惊讶的是，（1S，2R）-1-（6-氨基嘌呤-9-基）-2-（羟甲基）环戊烷[（1S，2R）-6]的三磷酸酯及其对映体（1R，2S）-6出现为TdT的强抑制剂（Ki = 0.5和1.9 mM，Kmapp dATP = 40 mM），而所有其他酶的活性均未受到影响。

  DOI：

  10.1016/s0968-0896(98)00021-2
• 作为产物：
  描述：

  顺式-(2-氨基-环戊基)-甲醇 在 盐酸 、 氨 、 三乙胺 作用下， 以 甲醇 、 正丁醇 为溶剂， 反应 56.0h， 生成 [(1S,2R)-2-(6-aminopurin-9-yl)cyclopentyl]methanol
  参考文献：
  名称：

  A Novel Approach for the Virtual Screening and Rational Design of Anticancer Compounds

  摘要：

  A topological substructural approach to molecular design (TOSS-MODE) has been introduced for the selection and design of anticancer compounds. A quantitative model that discriminates anticancer compounds from the inactive ones in a training series was obtained. This model permits the correct classification of 91.43% of compounds in an external prediction set with only 1.43% of false actives and 7.14% of false inactives. The model developed is then used in a simulation of a virtual search for Ras FTase inhibitors; 87% of the Ras FTase inhibitors used in this simulated search were correctly classified, thus indicating the ability of the TOSS-MODE model of finding lead compounds with novel structures and mechanism of action. Finally, a series of carbonucleosides was designed, and the compounds were classified as active/inactive anticancer compounds by using the model developed here. From the compounds so-designed, 20 were synthesized and evaluated experimentally for their antitumor effects on the proliferation of murine leukemia cells (L1210/0) and human T-lymphocyte cells (Molt4/C8 and CEM/0); 80% of these compounds were well-classified, as active or inactive, and only two pairs of isomeric compounds were false actives. The chloropurine derivatives were the most active compounds, especially compounds 6c,d.

  DOI：

  10.1021/jm991172d

文献信息

• JPH0673059A
  申请人：——

  公开号：JPH0673059A

  公开（公告）日：1994-03-15
• A Novel Approach for the Virtual Screening and Rational Design of Anticancer Compounds
  作者：Ernesto Estrada、Eugenio Uriarte、Alina Montero、Marta Teijeira、Lourdes Santana、Erik De Clercq

  DOI：10.1021/jm991172d

  日期：2000.5.1

  A topological substructural approach to molecular design (TOSS-MODE) has been introduced for the selection and design of anticancer compounds. A quantitative model that discriminates anticancer compounds from the inactive ones in a training series was obtained. This model permits the correct classification of 91.43% of compounds in an external prediction set with only 1.43% of false actives and 7.14% of false inactives. The model developed is then used in a simulation of a virtual search for Ras FTase inhibitors; 87% of the Ras FTase inhibitors used in this simulated search were correctly classified, thus indicating the ability of the TOSS-MODE model of finding lead compounds with novel structures and mechanism of action. Finally, a series of carbonucleosides was designed, and the compounds were classified as active/inactive anticancer compounds by using the model developed here. From the compounds so-designed, 20 were synthesized and evaluated experimentally for their antitumor effects on the proliferation of murine leukemia cells (L1210/0) and human T-lymphocyte cells (Molt4/C8 and CEM/0); 80% of these compounds were well-classified, as active or inactive, and only two pairs of isomeric compounds were false actives. The chloropurine derivatives were the most active compounds, especially compounds 6c,d.
• Chemo-enzymatic synthesis of a new type of enantiomerically pure carbocyclic nucleoside analogues with strong inhibitory effects on terminal deoxynucleotidyl transferase
  作者：Fritz Theil、Sibylle Ballschuh、Sabine Flatau、Martin von Janta-Lipinski、Eckart Matthes

  DOI：10.1016/s0968-0896(98)00021-2

  日期：1998.6

  The synthesis of enantiomerically pure carbocyclic adenosine derivatives which have been prepared based on the kinetic resolution of a trans-2-(hydroxymethyl)cyclopentanol derivative is described. Their corresponding triphosphates were evaluated as inhibitors of DNA polymerase beta, terminal deoxynucleotidyl transferase (TdT), telomerase, Escherichia coli DNA polymerase I and reverse transcriptase

  描述了基于反式-2-（羟甲基）环戊醇衍生物的动力学拆分制备的对映体纯的碳环腺苷衍生物的合成。他们相应的三磷酸盐被评估为人类免疫缺陷病毒的DNA聚合酶β，末端脱氧核苷酸转移酶（TdT），端粒酶，大肠杆菌DNA聚合酶I和逆转录酶的抑制剂。令人惊讶的是，（1S，2R）-1-（6-氨基嘌呤-9-基）-2-（羟甲基）环戊烷[（1S，2R）-6]的三磷酸酯及其对映体（1R，2S）-6出现为TdT的强抑制剂（Ki = 0.5和1.9 mM，Kmapp dATP = 40 mM），而所有其他酶的活性均未受到影响。