acetic acid 3-(6-amino-8-bromopurin-9-yl)-propyl ester | 839725-89-2

• 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 3-(6-amino-8-bromopurin-9-yl)-propyl ester
• 英文别名: 3-(6-Amino-8-bromo-9H-purin-9-yl)propyl acetate；3-(6-amino-8-bromopurin-9-yl)propyl acetate
• CAS: 839725-89-2
• 化学式: C₁₀H₁₂BrN₅O₂
• 分子量: 314.142
• InChiKey: PKRHWDYXMVSYJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  18
• 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

反应信息

• 作为反应物：
  描述：

  acetic acid 3-(6-amino-8-bromopurin-9-yl)-propyl ester 在 硫脲 作用下， 以 正丁醇 为溶剂， 反应 3.0h， 以88%的产率得到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-(6-氨基-嘌呤-9-基)-丙烷-1-醇 在 吡啶 、 4-二甲氨基吡啶 、 溴 、 sodium acetate 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 acetic acid 3-(6-amino-8-bromopurin-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

• 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.