isobu acid | 673500-74-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: isobu acid
• 英文别名: 3-[(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]-2-[[(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]methyl]propanoic acid
• CAS: 673500-74-8
• 化学式: C₃₄H₅₂O₁₀
• 分子量: 620.781
• InChiKey: BSBLVHJNEWLYCK-YXLCXRNRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  44
• 可旋转键数：
  5
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  isobu acid 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以72%的产率得到ASK-isobuC(O)CH2PhCH2-N9-C6-(NH)CBz-adenine
  参考文献：
  名称：

  WO2007/67333

  摘要：

  公开号：
• 作为产物：
  描述：

  isobu-OH 在 ruthenium trichloride 、 sodium periodate 作用下， 生成 isobu acid
  参考文献：
  名称：

  以单一低剂量口服给药新的单体三恶烷和甲氟喹后，感染疟疾的小鼠至少可以存活 30 天†

  摘要：

  仅通过五个简单的步骤，天然三恶烷青蒿素的总产率为 48%，即可制备出热稳定和水解稳定的三恶烷氟苯胺4b。在一次口服剂量仅为 6.8 mg/kg 的单体三恶烷4b与 20 mg/kg 的盐酸甲氟喹组合后，所有感染疟疾的小鼠都至少活到感染后第 30 天。在这个存活组的五只小鼠中，四只（80%）完全治愈（血液中没有寄生虫），一只老鼠有 4% 的血液寄生虫血症。重要的是，这种使用单体三恶烷4b加盐酸甲氟喹的ACT 化疗的疗效明显优于相同条件下使用流行的三恶烷药物蒿甲醚加盐酸甲氟喹的疗效。

  DOI：

  10.1021/jm9005934

文献信息

• Malaria-Infected Mice Are Cured by Oral Administration of New Artemisinin Derivatives
  作者：Gary H. Posner、Wonsuk Chang、Lindsey Hess、Lauren Woodard、Sandra Sinishtaj、Aimee R. Usera、William Maio、Andrew S. Rosenthal、Alvin S. Kalinda、John G. D’Angelo、Kimberly S. Petersen、Remo Stohler、Jacques Chollet、Josefina Santo-Tomas、Christopher Snyder、Matthias Rottmann、Sergio Wittlin、Reto Brun、Theresa A. Shapiro

  DOI：10.1021/jm701168h

  日期：2008.2.1

  In four or five chemical steps from the 1,2,4-trioxane artemisinin, a new series of 23 trioxane dimers has been prepared. Eleven of these new trioxane dimers cure malaria-infected mice via oral dosing at 3 x 30 mg/kg. The clinically used trioxane drug sodium artesunate prolonged mouse average survival to 7.2 days with this oral dose regimen. In comparison, animals receiving no drug die typically on day 6-7 postinfection. At only 3 x 10 mg/kg oral dosing, seven dimers prolong the lifetime of malaria-infected mice to days 14-17, more than double the chemotherapeutic effect of sodium artesunate. Ten new trioxane dimers at only a single oral dose of 30 mg/kg prolong mouse average survival to days 8.7-13.7, and this effect is comparable to that of the fully synthetic trioxolane drug development candidate OZ277, which is in phase 11 clinical trials.
• [EN] TRIOXANE MONOMERS AND DIMERS<br/>[FR] MONOMÈRES ET DIMÈRES À BASE DE TRIOXANE
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2010135427A3

  公开（公告）日：2011-04-21
• Malaria-Infected Mice Are Cured by a Single Dose of Novel Artemisinin Derivatives
  作者：Gary H. Posner、Ik-Hyeon Paik、Wonsuk Chang、Kristina Borstnik、Sandra Sinishtaj、Andrew S. Rosenthal、Theresa A. Shapiro

  DOI：10.1021/jm070149m

  日期：2007.5.1

  We disclose here for the first time the curative activity of a new generation of trioxane dimers, designed logically and prepared easily from the natural trioxane artemisinin in only four or five chemical steps that would be easily accomplished also on a manufacturing scale. Four of these trioxane dimers cure malaria-infected mice after only a single subcutaneous dose, and two other dimers cure after three oral doses.
• Anticancer and Antimalarial Efficacy and Safety of Artemisinin-Derived Trioxane Dimers in Rodents
  作者：Gary H. Posner、Andrew J. McRiner、Ik-Hyeon Paik、Surojit Sur、Kristina Borstnik、Suji Xie、Theresa A. Shapiro、Adebusola Alagbala、Barbara Foster

  DOI：10.1021/jm0303711

  日期：2004.2.1

  In only four chemical steps from naturally occurring artemisinin (1), trioxane dimers 6 and 7 were prepared on a multigram scale in overall 32-44% yields. In mice, both isonicotinate N-oxide dimer 6 and isobutyric acid dimer 7 were considerably more antimalarially efficacious than clinically used sodium artesunate (2) via both oral and intravenous administration. In the transgenic adenocarcinoma of mouse prostate model, some of the trioxane dimers had potent anticancer activity.
• WO2007/67333
  申请人：——

  公开号：——

  公开（公告）日：——