2-amino-6-chloro-9-(cyclopentyl)-9H-purine | 151370-28-4

• 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-amino-6-chloro-9-(cyclopentyl)-9H-purine
• 英文别名: 6-chloro-9-cyclopentyl-9H-purin-2-amine；6-Chloro-9-cyclopentyl-9H-purin-2-ylamine；6-chloro-9-cyclopentylpurin-2-amine
• CAS: 151370-28-4
• 化学式: C₁₀H₁₂ClN₅
• 分子量: 237.692
• InChiKey: FBRQMOOURFSVIP-UHFFFAOYSA-N

物化性质

• 沸点：
  498.0±55.0 °C(Predicted)
• 密度：
  1.70±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  69.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-amino-6-chloro-9-(cyclopentyl)-9H-purine 在 溴 作用下， 以 水 为溶剂， 反应 74.17h， 以81%的产率得到2-amino-8-bromo-6-chloro-9-(cyclopentyl)-9H-purine
  参考文献：
  名称：

  Synthetic Routes to N-9 Alkylated 8-Oxoguanines; Weak Inhibitors of the Human DNA Glycosylase OGG1

  摘要：

  人类 8-氧代鸟嘌呤 DNA 糖基化酶 OGG1 参与碱基切除修复（BER），BER 是几种 DNA 修复机制之一，可以抵消化疗和放疗对癌症治疗的影响。我们设想，可能会在 9-烷基-8-氧代鸟嘌呤中发现有效的 OGG1 抑制剂。因此，我们探索了 8-氧代鸟嘌呤的合成路线，并将其作为 OGG1 抑制剂进行研究。最佳的反应顺序是从 6-氯鸟嘌呤开始，包括 N-9 烷基化、C-8 溴化，最后同时水解两种卤化物。只有当 N-取代基不符合溴化条件时，才应考虑在 N-烷基化之前进行溴化。研究发现，8-氧代鸟嘌呤是 OGG1 的弱抑制剂。2,6-卤代嘌呤水解过程中产生的副产物 6-氯-8-氧代嘌呤的抑制效果略好于相应的 8-氧代鸟嘌呤。

  DOI：

  10.3390/molecules200915944
• 作为产物：
  描述：

  环戊胺 在 盐酸 、 三乙胺 作用下， 以 N,N-二甲基乙酰胺 、 正丁醇 为溶剂， 反应 48.0h， 生成 2-amino-6-chloro-9-(cyclopentyl)-9H-purine
  参考文献：
  名称：

  Synthesis and in vitro evaluation of novel 2,6,9-trisubstituted purines acting as cyclin-dependent kinase inhibitors

  摘要：

  Novel C-2, C-6, N-9 trisubstituted purines derived from the olomoucine/roscovitine lead structure were synthesized and evaluated for their ability to inhibit starfish oocyte CDK1/cyclin B, neuronal CDK5/p35 and erk1 kinases in purified extracts. Structure-activity relationship studies showed that increased steric bulk at N-9 reduces the inhibitory potential whereas substitution of the aminoethanol C-2 side chain by various groups of different size (methyl, propyl, butyl, phenyl, benzyl) only slightly decreases the activity when compared to (R)-roscovitine. Optimal inhibitory activity against CDK5, CDK1 and CDK2, with IC50 values of 0.16, 0.45 and 0.65 mu M, respectively, was obtained with compound 21 containing a (2R)-pyrrolidin-2-yl-methanol substituent at the C-2 and a 3-iodobenzylamino group at the C-6 of the purine. Compound 21 proved cytotoxic against human tumor HeLa cells (LD50 = 6.7 mu M versus 42.7 mu M for olomoucine, 24-h contact). Furthermore, unlike olomoucine, compound 21 was effective upon short exposure (LD50 = 25.3 mu M, 2-h contact). The available data suggest that the affinity for CDKs and the cytotoxic potential of the drugs are inter-related. However, no straightforward cell cycle phase specificity of the cytotoxic response to 21 was observed in synchronized HeLa cells. With the noticeable exception of pronounced lengthening of the S-phase transit by 21 applied during early-S in synchronized HeLa cells, and in striking contrast with earlier reports on studies using plant or echinoderm cells, olomoucine and compound 21 were unable to reversibly arrest cell cycle progression in asynchronous growing HeLa cells. Some irreversible block in G1 and G2 phase occurred at high olomoucine concentration, correlated with induced cell death. Moreover, chronic exposure to lethal doses of compound 21 resulted in massive nuclear fragmentation, evocative of mitotic catastrophe with minor amounts of apoptosis only. It was also found that olomoucine and compound 21 reversibly block the intracellular uptake of nucleosides with high efficiency. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00064-4

文献信息

• New Purine Derivatives as Efficient Preparation of Nucleoside Analogs via Alkylation
  作者：Kirill A. Lukin、Chengxi Yang、John R. Bellettini、B. A. Narayanan

  DOI：10.1080/15257770008035027

  日期：2000.4

  New diazabicycloundecenium and phosphazenium derivatives of purines are introduced for mild and efficient preparation of nucleoside analogs via in situ alkylation. Diazabicycloundecenium salts of purines were obtained directly as a result of an unusual reaction between two corresponding amino compounds.

  引入了新的嘌呤二氮杂双环烯鎓和磷氮烯鎓衍生物，用于通过原位烷基化温和有效地制备核苷类似物。由于两个相应的氨基化合物之间发生异常反应，因此直接获得了嘌呤的二氮杂双环ce盐。
• Regioselective alkylation reaction of purines under microwave irradiation
  作者：Arturo Vinuesa、Miquel Viñas、Daniel Jahani、Jaume Ginard、Nuria Mur、Maria Dolors Pujol

  DOI：10.1002/jhet.4407

  日期：2022.3

  The alkylation of purines which is generally carried out after anion formation by treatment with a base and alkyl halide is complicated and in the best cases, mixtures of N-alkylated compounds are obtained. Purine derivatives can be acquired from alkylation at N-7 and N-9. In this work, the reaction conditions have been optimized to obtain the alkylation products of N-9 regioselectively. Different

  通常在阴离子形成后通过用碱和烷基卤处理进行的嘌呤烷基化是复杂的，并且在最好的情况下，获得了N-烷基化化合物的混合物。嘌呤衍生物可以从N -7 和N -9 的烷基化中获得。在这项工作中，对反应条件进行了优化，以区域选择性地获得N -9 的烷基化产物。已经尝试了不同的碱，氢氧化四丁基铵产生了最好的结果。反应取决于所使用的碱和溶剂的类型，并且在使用微波辐照的帮助下显着改善，这也通过减少副产物的形成而显着减少了反应时间。
• [EN] SYNTHESIS OF ACYCLIC NUCLEOSIDE DERIVATIVES<br/>[FR] SYNTHESE DE DERIVES DE NUCLEOSIDE ACYCLIQUE
  申请人：MEDIVIR AB

  公开号：WO2000008025A1

  公开（公告）日：2000-02-17

  Novel intermediates and improvements in the synthesis of acyclic guanine nucleoside prodrugs of the formula (R)-9-[(2-alkanoylmethyl)-4-(aminoacyloxy)butyl]guanine (for example valtamociclovir stearate), including purine salts amenable to one pot alkylation with the acyclic side chain, acyclic 2-amino-6-halo-purine and protected guanine precursors, one pot manipulations thereof and last step work up procedures.

  一种无环鸟嘌呤核苷前药的合成中间体和改进方法的新颖方法，其化学式为（R）-9-[(2-烷酰甲基)-4-(氨基酰氧基)丁基]鸟嘌呤（例如硬膜外瓣状病毒酯）包括能够进行一锅法烷基化的嘌呤盐，无环2-氨基-6-卤代嘌呤和保护鸟嘌呤前体，以及一锅法操作和最后步骤的处理程序。
• Second-Generation AUTACs for Targeted Autophagic Degradation
  作者：Daiki Takahashi、Taiichi Ora、Shigekazu Sasaki、Naoki Ishii、Toshio Tanaka、Takumi Matsuda、Mutsuki Ikeda、Jun Moriyama、Nobuo Cho、Hiroshi Nara、Hironobu Maezaki、Masahiro Kamaura、Kenichiro Shimokawa、Hirokazu Arimoto

  DOI：10.1021/acs.jmedchem.3c00861

  日期：2023.9.14

  Targeted protein degradation via the ubiquitin-proteasome system has emerged as one of the most promising drug discovery modalities. Autophagy, another intracellular degradation system, can target a wide range of nonproteinous substrates as well as proteins, but its application to targeted degradation is still in its infancy. Our previous work revealed a relationship between guanine modification of

  通过泛素-蛋白酶体系统进行的靶向蛋白质降解已成为最有前途的药物发现方式之一。自噬是另一种细胞内降解系统，可以靶向多种非蛋白质底物以及蛋白质，但其在靶向降解中的应用仍处于起步阶段。我们之前的工作揭示了细胞内蛋白质上半胱氨酸残基的鸟嘌呤修饰与选择性自噬之间的关系，从而产生了第一个基于自噬的降解剂，即自噬靶向嵌合体（AUTAC）。基于研究背景，所有报道的AUTACs化合物都含有半胱氨酸作为子结构。在这里，我们通过进行 SAR 研究来检查该子结构的重要性，并报告通过用其他部分替换半胱氨酸来显着改善降解剂的活性。几种衍生物表现出亚μM范围的降解活性，证明了AUTAC增加的实用价值。
• Synthesis of acyclic nucleoside derivatives
  申请人：Medivir Aktiebolag

  公开号：EP1535923A1

  公开（公告）日：2005-06-01

  A process for preparing a compound of the formula: wherein R10 is a C3-C21 saturated or monounsaturated, optionally substituted alkyl residue, the process comprising the steps of: a) reacting a compound of the formula: wherein R6 and R7 are lower alkyl or benzyl residues, or R6 and R7 taken together are -CH2CH2-, -CH2CH2CH2- or -CH2CH2CH2CH2- with R10COOH or an activated derivative thereof, wherein R10 is a C3-C21 saturated or monounsaturated, optionally substituted alkyl residue, to provide a compound of the formula: wherein R6, R7 and R10 are defined as above, b) de-protecting the acetal of the product of step a), and c) reducing the aldehyde substituent of the product of step b), characterized in that the products of steps a) and b) are not isolated.

  一种制备式化合物的工艺： 其中R10为C3-C21饱和或单不饱和、任选取代的烷基残基，该工艺包括以下步骤 a)反应式如下的化合物 其中 R6 和 R7 是低级烷基或苄基残基，或 R6 和 R7 合起来是-CH2CH2-、-CH2CH2CH2-或 -CH2CH2CH2-与 R10COOH 或其活化衍生物反应、 其中 R10 是 C3-C21 饱和或单不饱和、任选取代的烷基残基，以提供式化合物： 其中 R6、R7 和 R10 定义如上、 b) 对步骤 a) 产物的缩醛进行脱保护，以及 c) 还原步骤 b) 产物中的醛取代基、 其特征在于，步骤 a) 和 b) 的产物不分离。