acetic acid 2-(6-aminopurin-9-yl)-ethyl ester | 5845-43-2

• 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: acetic acid 2-(6-aminopurin-9-yl)-ethyl ester
• 英文别名: Acetic acid 2-(6-amino-purin-9-yl)-ethyl ester；2-(6-aminopurin-9-yl)ethyl acetate
• CAS: 5845-43-2
• 化学式: C₉H₁₁N₅O₂
• 分子量: 221.219
• InChiKey: JRMMAACZJOVVCV-UHFFFAOYSA-N

物化性质

• 熔点：
  175-177 °C
• 沸点：
  453.4±55.0 °C(Predicted)
• 密度：
  1.52±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  95.9
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  acetic acid 2-(6-aminopurin-9-yl)-ethyl ester 在 potassium tert-butylate 、 溴 、 sodium acetate 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.75h， 生成 acetic acid 2-[6-amino-8-(7-chlorobenzothiazol-2-ylsulfanyl)-purin-9-yl]-ethyl ester
  参考文献：
  名称：

  7‘-Substituted Benzothiazolothio- and Pyridinothiazolothio-Purines as Potent Heat Shock Protein 90 Inhibitors

  摘要：

  We report on the discovery of benzo- and pyridino-thiazolothiopurines as potent heat shock protein 90 inhibitors. The benzothiazole moiety is exceptionally sensitive to substitutions on the aromatic ring with a 7'-substituent essential for activity. Some of these compounds exhibit low nanomolar inhibition activity in a Her-2 degradation assay (28-150 nM), good aqueous solubility, and oral bioavailability profiles in mice. In vivo efficacy experiments demonstrate that compounds of this class inhibit tumor growth in an N87 human colon cancer xenograft model via oral administration as shown with compound 37 (8-(7-chlorobenzothiazol-2- ylsulfanyl)-9-(2-cyclopropylamino-ethyl)-9H-purin-6-ylamine).

  DOI：

  10.1021/jm051146h
• 作为产物：
  描述：

  腺嘌呤 、 alkaline earth salt of/the/ methylsulfuric acid 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以91%的产率得到acetic acid 2-(6-aminopurin-9-yl)-ethyl ester
  参考文献：
  名称：

  7‘-Substituted Benzothiazolothio- and Pyridinothiazolothio-Purines as Potent Heat Shock Protein 90 Inhibitors

  摘要：

  We report on the discovery of benzo- and pyridino-thiazolothiopurines as potent heat shock protein 90 inhibitors. The benzothiazole moiety is exceptionally sensitive to substitutions on the aromatic ring with a 7'-substituent essential for activity. Some of these compounds exhibit low nanomolar inhibition activity in a Her-2 degradation assay (28-150 nM), good aqueous solubility, and oral bioavailability profiles in mice. In vivo efficacy experiments demonstrate that compounds of this class inhibit tumor growth in an N87 human colon cancer xenograft model via oral administration as shown with compound 37 (8-(7-chlorobenzothiazol-2- ylsulfanyl)-9-(2-cyclopropylamino-ethyl)-9H-purin-6-ylamine).

  DOI：

  10.1021/jm051146h

文献信息

• Lead optimization and biological evaluation of fragment-based cN-II inhibitors
  作者：Rémi Guillon、Rahila Rahimova、Preeti、David Egron、Sonia Rouanet、Charles Dumontet、Nushin Aghajari、Lars Petter Jordheim、Laurent Chaloin、Suzanne Peyrottes

  DOI：10.1016/j.ejmech.2019.02.040

  日期：2019.4

  The development of cytosolic 5′-nucleotidase II (cN-II) inhibitors is essential to validate cN-II as a potential target for the reversion of resistance to cytotoxic nucleoside analogues. We previously reported a fragment-based approach combined with molecular modelling, herein, the selected hit-fragments were used again in another computational approach based on the Ilib-diverse (a software enabling

  胞质5'-核苷酸酶II（cN-II）抑制剂的开发对于验证cN-II作为逆转对细胞毒性核苷类似物的耐药性的潜在靶点至关重要。我们之前曾报道过基于片段的方法与分子建模相结合，在此，所选的命中片段再次用于基于Ilib-diverse（可通过基于片段的从头设计构建虚拟分子库的软件）的另一种计算方法中生成潜在抑制剂的重点文库。选择了与先前鉴定的化合物有关的分子支架，并产生了一系列新的化合物。19种衍生物中有10种对200μM纯化的重组蛋白表现出50-75％的抑制作用，其中3种衍生物（12、13和18）的K i处于亚毫摩尔范围内（分别为0.84、2.4和0.58 mM）。尽管仅适度的效力，但cN-II抑制剂与细胞毒性嘌呤核苷类似物联合使用对癌细胞具有协同作用。因此，这些衍生物代表一类非核（t）idic cN-II抑制剂，具有克服癌症耐药性的潜在效用，特别是在血液恶性肿瘤中，其中cN-II活性已被描述为重要参数。
• Orally Active Purine-Based Inhibitors of Heat Shock Protein 90
  申请人：Kasibhatla R. Srinivas

  公开号：US20070129334A1

  公开（公告）日：2007-06-07

  Novel purine compounds and tautomers and pharmaceutically acceptable salts thereof are described, as are pharmaceutical compositions comprising the same, complexes comprising the same, e.g., HSP90 complexes, and methods of using the same. Methods of using the novel purine compounds of the invention, and tautomers and pharmaceutically acceptable salts thereof, include their use in inhibiting heat shock protein 90's (HSP90's) to thereby treat or prevent HSP90-dependent diseases, e.g., proliferative disorders such as breast cancer.

  本发明描述了新型嘌呤化合物及其互变异构体和药学上可接受的盐，以及包含它们的制药组合物、包含它们的复合物（例如HSP90复合物）和使用它们的方法。使用本发明的新型嘌呤化合物、互变异构体和药学上可接受的盐的方法包括在抑制热休克蛋白90（HSP90）中使用它们，从而治疗或预防HSP90依赖性疾病，例如增生性疾病如乳腺癌。
• Orally Active Purine-Based Inhibitors of the Heat Shock Protein 90
  作者：Marco A. Biamonte、Jiandong Shi、Kevin Hong、David C. Hurst、Lin Zhang、Junhua Fan、David J. Busch、Patricia L. Karjian、Angelica A. Maldonado、John L. Sensintaffar、Yong-Ching Yang、Adeela Kamal、Rachel E. Lough、Karen Lundgren、Francis J. Burrows、Gregg A. Timony、Marcus F. Boehm、Srinivas R. Kasibhatla

  DOI：10.1021/jm0503087

  日期：2006.1.1

  Orally active Hsp90 inhibitors are of interest as potential chemotherapeutic agents. Recently, fully synthetic 8-benzyladenines and 8-sulfanyladenines such as 4 were disclosed as Hsp90 inhibitors, but these compounds are not water soluble and consequently have unacceptably low oral bioavailabilities. We now report that water-solubility can be achieved by inserting an amino functionality in the N(9) side chain. This results in compounds that are potent, soluble in aqueous media, and orally bioavailable. In an HER-2 degradation assay, the highest potency was achieved with the neopentylamine 42 (HER-2 IC50 = 90 nM). In a murine tumor xenograft model (using the gastric cancer cell line N87), the H3PO4 salts of the amines 38, 39, and 42 induced tumor growth inhibition when administered orally at 200 mg/kg/day. The amines 38, 39, and 42 are the first Hsp90 inhibitors shown to inhibit tumor growth upon oral dosage.
• ORALLY ACTIVE PURINE-BASED INHIBITORS OF HEAT SHOCK PROTEIN 90
  申请人：Conforma Therapeutics Corporation

  公开号：EP1962863A2

  公开（公告）日：2008-09-03
• [EN] ORALLY ACTIVE PURINE-BASED INHIBITORS OF HEAT SHOCK PROTEIN 90<br/>[FR] INHIBITEURS A BASE DE PURINE ORALEMENT ACTIFS DE LA PROTEINE DE CHOC THERMIQUE 90
  申请人：CONFORMA THERAPEUTICS CORP

  公开号：WO2007075572A2

  公开（公告）日：2007-07-05

  [EN] Novel purine compounds and tautomers and pharmaceutically acceptable salts thereof are described, as are pharmaceutical compositions comprising the same, complexes comprising the same, e.g., HSP90 complexes, and methods of using the same. Methods of using the novel purine compounds of the invention,and tautomers and pharmaceutically acceptable salts thereof, include their use in inhibiting heat shock protein 90's (HSP90*s) to thereby treat or prevent HSP90-dependent diseases, e.g., proliferative disorders such as breast cancer.
  [FR] La présente invention concerne des composés de purine innovants, leurs tautomères et leurs sels pharmaceutiquement acceptables ainsi que les compositions pharmaceutiquement et les complexes qui les comprennent, par exemple les complexes de HSP90, et leurs procédés d'utilisation. Les procédés d'utilisation des composés de purine innovants de l'invention, de leurs tautomères et de leurs sels pharmaceutiquement acceptables incluent leur utilisation pour inhiber les protéines de choc thermique 90 (HSP90) afin de traiter ou de prévenir les maladies liées aux HSP90, par exemple les troubles prolifératifs tels que le cancer du sein.