isobu-OH | 673500-72-6

• 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-OH
• 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]propan-1-ol
• CAS: 673500-72-6
• 化学式: C₃₄H₅₄O₉
• 分子量: 606.797
• InChiKey: PIHGTXTYUJXWMZ-MDAXRCBMSA-N

物化性质

• 熔点：
  81-82 °C
• 沸点：
  645.7±55.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  43
• 可旋转键数：
  5
• 环数：
  10.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  94.1
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  isobu-OH 在 sodium hydride 、 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 48.5h， 以57%的产率得到WC-isobu-OCH2Pyr
  参考文献：
  名称：

  WO2007/67333

  摘要：

  公开号：
• 作为产物：
  描述：

  dihydroartemisinin 在 4-二甲氨基吡啶 、 dimethyl sulfide borane 、 四氯化锡 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 41.5h， 生成 isobu-OH
  参考文献：
  名称：

  青蒿素衍生的二聚体、三聚体和树枝状聚合物的合成：研究它们的抗疟和抗病毒活性，包括推定的作用机制

  摘要：

  生物活性化合物的二聚体、三聚体和树枝状聚合物的生成是最近为发现新的有效候选药物而开发的一种方法。在此，我们展示了新的青蒿素衍生二聚体和树枝状聚合物的合成，并研究了它们对疟原虫恶性疟原虫3D7 株和人巨细胞病毒 (HCMV) 的作用。二聚体7是最活跃的化合物（EC 50 1.4Ñ米）在抗疟疾功效方面，是更有效的比标准药物双氢青蒿素（EC 50 2.4Ñ米），artesunic酸（EC 50 8.9Ñ米）和氯喹（EC 50为9.8N米）。Trimer 4作为体外抗 HCMV 复制中最具活性的药物脱颖而出，其 EC 50值为 0.026 μm，比两种参考药物更昔洛韦 (EC 50 2.60 μm ) 和青蒿琥酯 (EC 50 5.41 ) 的活性更高μ米）。此外，青蒿素衍生的二聚体13和三聚体15首次固定在 TOYOPEARL AF-Amino-650M 珠上，并用于使用 HCMV 感染的原代人

  DOI：

  10.1002/chem.201800729

文献信息

• Antimalarial chemotherapy: Orally curative artemisinin-derived trioxane dimer esters
  作者：Ryan C. Conyers、Jennifer R. Mazzone、Abhai K. Tripathi、David J. Sullivan、Gary H. Posner

  DOI：10.1016/j.bmcl.2014.11.064

  日期：2015.1

  Eight new artemisinin-derived trioxane dimer esters 5 have been prepared and tested for antimalarial efficacy in malaria-infected mice. At a single oral dose of only 6 mg/kg combined with 18 mg/kg of mefloquine, each of the dimer esters 5 outperformed the antimalarial drug artemether (2). The most efficacious dimer, dichlorobenzoate ester 5h, prolonged mouse survival past day 30 of infection with three

  已经制备了八种新的青蒿素衍生三恶烷二聚体酯5 ，并测试了其在感染疟疾的小鼠中的抗疟功效。在仅 6 mg/kg 的单次口服剂量与 18 mg/kg 甲氟喹组合时，每种二聚体酯5的效果均优于抗疟药物蒿甲醚 ( 2 )。最有效的二聚体二氯苯甲酸酯5h延长了小鼠感染后第 30 天的存活时间，该组中的四只小鼠中的三只没有检测到寄生虫血症，并且在第 30 天时表现健康。
• Malaria-Infected Mice Are Cured by a Single Oral Dose of New Dimeric Trioxane Sulfones Which Are Also Selectively and Powerfully Cytotoxic to Cancer Cells
  作者：Andrew S. Rosenthal、Xiaochun Chen、Jun O. Liu、Diana C. West、Paul J. Hergenrother、Theresa A. Shapiro、Gary H. Posner

  DOI：10.1021/jm801484v

  日期：2009.2.26

  A new series of 6 dimeric trioxane sulfones has been prepared from the natural trioxane artemisinin in five or six chemical steps. One of these thermally and hydrolytically stable new chemical entities (4c) completely cured malaria-infected mice via a single oral dose of 144 mg/kg. At a much lower single oral dose of only 54 mg/kg combined with 13 mg/kg of mefloquine hydrochloride, this trioxane dimer

  通过五六个化学步骤，从天然三恶烷青蒿素中制备了一系列新的 6 聚三恶烷砜。这些热和水解稳定的新化学实体之一 ( 4c ) 通过单次口服剂量 144 mg/kg 完全治愈了感染疟疾的小鼠。在仅 54 mg/kg 的低得多的单次口服剂量与 13 mg/kg 的盐酸甲氟喹组合下，这种三恶烷二聚体4c及其母体三恶烷二聚体4b也完全治愈了感染疟疾的小鼠。二聚体4c和4b均对五种癌细胞系具有有效且选择性的细胞毒性。
• Malaria-Infected Mice Live until at Least Day 30 after a New Monomeric Trioxane Combined with Mefloquine Are Administered Together in a Single Low Oral Dose
  作者：Lauren E. Woodard、Wonsuk Chang、Xiaochun Chen、Jun O. Liu、Theresa A. Shapiro、Gary H. Posner

  DOI：10.1021/jm9005934

  日期：2009.12.10

  from the natural trioxane artemisinin, the thermally and hydrolytically stable trioxane fluoroanilide 4b has been prepared. Upon one oral dose of only 6.8 mg/kg of monomeric trioxane 4b combined with 20 mg/kg of mefloquine hydrochloride, all of the malaria-infected mice lived until at least day 30 post infection. Of the five mice in this surviving group, four (80%) were completely cured (no parasites

  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。
• Biological Mechanisms of Action of Novel C-10 Non-Acetal Trioxane Dimers in Prostate Cancer Cell Lines
  作者：Adebusola A. Alagbala、Andrew J. McRiner、Kristina Borstnik、Tanzina Labonte、Wonsuk Chang、John G. D'Angelo、Gary H. Posner、Barbara A. Foster

  DOI：10.1021/jm060803i

  日期：2006.12.1

  The mechanisms of action of three C-10 non-acetal trioxane dimers (TDs) were examined in human (LNCaP) and mouse (TRAMP-C1A and -C2H) prostate cancer cell lines. 1 (AJM3/23), 2 (GHP-TM-III-07w), and 3 (GHP-KB-06) inhibited cell growth with 3 being the most potent in C1A (GI(50) = 18.0 nM), C2H (GI(50) = 17.0 nM), and LNCaP (GI(50) = 17.9 nM) cells. In comparison to a standard cytotoxic agent such as doxorubicin (GI(50) = 45.3 nM), 3 (GI(50) = 17.9 nM) inhibited LNCaP cell growth more potently. TDs induced G(0)/G(1) cell cycle arrest in LNCaP cells and decreased cells in the S phase. These changes correlated with modulation of G(1) phase cell cycle proteins including decreased cyclin D1, cyclin E, and cdk2 and increased p21(waf1) and p27(Kip1). TDs also promoted apoptosis in LNCaP cells with increased expression of proapoptotic bax. These results demonstrate that TDs are potentially useful agents that warrant further preclinical development for treatment of prostate cancer.
• 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.