acetic acid 3-(6-aminopurin-9-yl)-propyl ester | 5845-42-1

• 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: acetic acid 3-(6-aminopurin-9-yl)-propyl ester
• 英文别名: acetic acid 3-(6-aminopurin-9-yl)propyl ester；9-(3-acetoxypropyl)adenine；1-acetoxy-3-(6-amino-purin-9-yl)-propane；9-(3-Acetoxypropyl)adenin；3-(6-amino-9H-purin-9-yl)propyl acetate；3-(6-aminopurin-9-yl)propyl acetate
• CAS: 5845-42-1
• 化学式: C₁₀H₁₃N₅O₂
• 分子量: 235.246
• InChiKey: UMQCBOPIPHSVMU-UHFFFAOYSA-N

物化性质

• 沸点：
  465.4±55.0 °C(Predicted)
• 密度：
  1.45±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 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 3-(6-aminopurin-9-yl)-propyl ester 在 溴 、 溶剂黄146 、 硫脲 作用下， 以 甲醇 、 二氯甲烷 、 正丁醇 为溶剂， 反应 4.0h， 生成 acetic acid 3-(6-amino-8-thioxo-7,8-dihydropurin-9-yl)propyl ester
  参考文献：
  名称：

  在温和的好氧条件下用重氮盐制备8-（芳基硫烷基）ni啶

  摘要：

  8-（芳基硫基）腺嘌呤11是在高达75％的收率由8- thionoadenine反应制备6（乙酸3-（6-氨基-8-硫代-7,8- dihydropurin -9-基）丙基酯）与DMSO中的四氟硼酸苯重氮盐。带有吸电子取代基的苯二氮杂zon离子的收率最高。该反应在室温下没有任何碱的条件下平稳进行，可以在空气气氛下进行。极端温和的条件可与各种官能团兼容。

  DOI：

  10.1021/jo048522a
• 作为产物：
  描述：

  3-(5-amino-6-chloropyrimidin-4-ylamino)propan-ol 在 吡啶 、 4-二甲氨基吡啶 、 氨 、 乙酸酐 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 acetic acid 3-(6-aminopurin-9-yl)-propyl 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

• Intramolecular Cyclization of Some Acyclic Nucleoside Analogs
  作者：Zlatko Janeba、Antonín Holý、Hana Votavová、Milena Masojídková

  DOI：10.1135/cccc19960442

  日期：——

  Reaction of stereoisomeric 8-bromo-9-(2,3-O-isopropylidene-2,3,4-trihydroxybutyl)adenines (8) with concentrated aqueous ammonia, sodium hydride, potassium tert-butoxide, or 1,8-diazabicyclo[5,4,0]undec-7-ene afforded 4e-O,8-anhydro-9-(2,3-O-isopropylidene-2,3,4-trihydroxybutyl)adenines 9 (derivatives of 1,3-oxazepino[2,3-e]adenine). The CD spectra of optically active stereoisomers of 9 have been studied and it was found that for threo isomers 9a and 9b their character corresponds to 5'-O,8-cycloadenosine. The compounds 9 were also prepared by oxidative cyclization of 9-(2,3-O-isopropylidene-2,3,4-trihydroxybutyl)adenines (7) with lead(IV) acetate in benzene. Reaction of 9-(4-hydroxybutyl)adenine (14) with lead(IV) acetate smoothly afforded the seven-membered ring derivative, 4'-O,8-anhydro-9-(4-hydroxybutyl)adenine (15); no anhydro products with five-, six-, and eight-membered ring were found. 2',3'-O-Isopropylideneinosine (16) reacted with lead(IV) acetate to give 5'-O,8-cyclo-2',3'-O-isopropylideneinosine (17) whereas 9-(4-hydroxybutyl)hypoxanthine (18) afforded no cyclic products.

  立体异构体8-溴-9-(2,3-O-异丙基-2,3,4-三羟基丁基)腺嘌呤（8）与浓氨水、氢化钠、叔丁醇钾或1,8-二氮杂双环[5,4,0]十一烯反应，得到4e-O,8-去水-9-(2,3-O-异丙基-2,3,4-三羟基丁基)腺嘌呤9（1,3-噁唑并[2,3-e]腺嘌呤的衍生物）。对9的光学活性立体异构体的CD光谱进行了研究，发现对于threo异构体9a和9b，它们的特征对应于5'-O,8-环腺苷。化合物9也可以通过9-(2,3-O-异丙基-2,3,4-三羟基丁基)腺嘌呤（7）与醋酸铅（IV）在苯中氧化环化制备而成。9-(4-羟基丁基)腺嘌呤（14）与醋酸铅（IV）反应顺利地得到七元环衍生物4'-O,8-去水-9-(4-羟基丁基)腺嘌呤（15）；没有发现五元、六元和八元环的去水产物。2',3'-O-异丙基核苷（16）与醋酸铅（IV）反应，得到5'-O,8-环-2',3'-O-异丙基核苷（17），而9-(4-羟基丁基)次黄嘌呤（18）没有产生环状产物。
• 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.
• 7‘-Substituted Benzothiazolothio- and Pyridinothiazolothio-Purines as Potent Heat Shock Protein 90 Inhibitors
  作者：Lin Zhang、Junhua Fan、Khang Vu、Kevin Hong、Jean-Yves Le Brazidec、Jiandong Shi、Marco Biamonte、David J. Busch、Rachel E. Lough、Roy Grecko、Yingqing Ran、John L. Sensintaffar、Adeela Kamal、Karen Lundgren、Francis J. Burrows、Robert Mansfield、Gregg A. Timony、Edgar H. Ulm、Srinivas R. Kasibhatla、Marcus F. Boehm

  DOI：10.1021/jm051146h

  日期：2006.8.1

  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).
• Preparation of 8-(Arylsulfanyl)adenines with Diazonium Salts under Mild, Aerobic Conditions
  作者：Marco A. Biamonte、Jiandong Shi、David Hurst、Kevin Hong、Marcus F. Boehm、Srinivas R. Kasibhatla

  DOI：10.1021/jo048522a

  日期：2005.1.1

  Benzenediazonium ions carrying an electron-withdrawing substituent gave the highest yields. The reaction proceeded smoothly at room temperature without any base and could be performed under air atmosphere. The extremely mild conditions are compatible with a wide range of functional groups.

  8-（芳基硫基）腺嘌呤11是在高达75％的收率由8- thionoadenine反应制备6（乙酸3-（6-氨基-8-硫代-7,8- dihydropurin -9-基）丙基酯）与DMSO中的四氟硼酸苯重氮盐。带有吸电子取代基的苯二氮杂zon离子的收率最高。该反应在室温下没有任何碱的条件下平稳进行，可以在空气气氛下进行。极端温和的条件可与各种官能团兼容。