Valeriansaeure-(2,2,2-trichlor-ethylester) | 1617-03-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: Valeriansaeure-(2,2,2-trichlor-ethylester)
• 英文别名: 2,2,2-Trichloroethyl pentanoate
• CAS: 1617-03-4
• 化学式: C₇H₁₁Cl₃O₂
• 分子量: 233.522
• InChiKey: IQMBQFVYGSNNES-UHFFFAOYSA-N

物化性质

• 沸点：
  103.0-103.5 °C(Press: 10.5-11.0 Torr)
• 密度：
  1.284±0.06 g/cm3(Predicted)
• 保留指数：
  1286;1277;1278;1284;1289;1309;1239

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  12
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  Valeriansaeure-(2,2,2-trichlor-ethylester) 以 乙腈 为溶剂， 反应 1.0h， 生成 Pentanoic acid (2R,3S,4S,5R)-4-hydroxy-5-(6-methoxy-purin-9-yl)-2-pentanoyloxymethyl-tetrahydro-furan-3-yl ester
  参考文献：
  名称：

  Di- and triester prodrugs of the varicella-zoster antiviral agent 6-methoxypurine arabinoside

  摘要：

  6-Methoxypurine arabinoside (9-beta-D-arabinofuranosyl-6-methoxy-9H-purine, 1) has potent and selective activity against varicella-zoster virus in vitro. An unfavorable metabolic profile observed with oral dosing in the rat led to the preparation of a variety of 2',3',5'-triesters (2a-n) and several 2',3'-, 2',5'-, and 3',5-diester, of this arabinoside (3a-n, 4a-f, and 5a-j, respectively). The compounds were evaluated as prodrugs by measuring the urinary levels of 1 in rat urine after oral dosing. With the exception of triacetate 2a, the triesters failed to significantly enhance bioavailability. Administration of compound 2a resulted in a 3-fold increase in systemic availability of 1, possibly because of its increased water solubility (1.6 times more soluble than 1) and only slightly increased relative log P value (1.93 vs 0.50 for 1). The longer chain aliphatic triesters and aromatic triesters had lower water solubilities and increased lipophilic partitioning. These factors might account for the lower systemic bioavailability of these compounds. In contrast, the diesters, especially the aliphatic diesters, showed significantly improved systemic availability. This might be a consequence of the higher aqueous solubilities and enhanced partition coefficients seen with these compounds. 2',3-Diacetate 3a showed the best combination of high systemic availability and water solubility of all the prodrugs of 1.

  DOI：

  10.1021/jm00079a006
• 作为产物：
  描述：

  2,2,2-三氯乙醇 、 戊酰氯 在 吡啶 作用下， 生成 Valeriansaeure-(2,2,2-trichlor-ethylester)
  参考文献：
  名称：

  Di- and triester prodrugs of the varicella-zoster antiviral agent 6-methoxypurine arabinoside

  摘要：

  6-Methoxypurine arabinoside (9-beta-D-arabinofuranosyl-6-methoxy-9H-purine, 1) has potent and selective activity against varicella-zoster virus in vitro. An unfavorable metabolic profile observed with oral dosing in the rat led to the preparation of a variety of 2',3',5'-triesters (2a-n) and several 2',3'-, 2',5'-, and 3',5-diester, of this arabinoside (3a-n, 4a-f, and 5a-j, respectively). The compounds were evaluated as prodrugs by measuring the urinary levels of 1 in rat urine after oral dosing. With the exception of triacetate 2a, the triesters failed to significantly enhance bioavailability. Administration of compound 2a resulted in a 3-fold increase in systemic availability of 1, possibly because of its increased water solubility (1.6 times more soluble than 1) and only slightly increased relative log P value (1.93 vs 0.50 for 1). The longer chain aliphatic triesters and aromatic triesters had lower water solubilities and increased lipophilic partitioning. These factors might account for the lower systemic bioavailability of these compounds. In contrast, the diesters, especially the aliphatic diesters, showed significantly improved systemic availability. This might be a consequence of the higher aqueous solubilities and enhanced partition coefficients seen with these compounds. 2',3-Diacetate 3a showed the best combination of high systemic availability and water solubility of all the prodrugs of 1.

  DOI：

  10.1021/jm00079a006

文献信息

• 9-.beta.-D-arabinofuranasyl-2-amino-6-methaoxy-9H-purine
  申请人：Burroughs Wellcome Co.

  公开号：US05424295A1

  公开（公告）日：1995-06-13

  The compound 9-B-D-arabinofuranosyl-2-amino-6-methoxy-9H-purine along with its 5'-acetyl and 5'-(4-methoxy-4-oxobutyryl derivatives are disclosed as inhibitors of Varicella Zoster virus (VZV).

  化合物9-B-D-阿拉伯糖呋喃基-2-氨基-6-甲氧基-9H-嘌呤及其5'-乙酰基和5'-(4-甲氧基-4-氧代丁酰基)衍生物被披露为水痘-带状疱疹病毒（VZV）的抑制剂。
• US5424295A
  申请人：——

  公开号：US5424295A

  公开（公告）日：1995-06-13
• US5539098A
  申请人：——

  公开号：US5539098A

  公开（公告）日：1996-07-23
• US9303497B2
  申请人：——

  公开号：US9303497B2

  公开（公告）日：2016-04-05
• US9322269B2
  申请人：——

  公开号：US9322269B2

  公开（公告）日：2016-04-26