2-(trans-4-tert-butylcyclohexyl)methyl-3-hydroxynaphtho-1,4-quinone | 86790-15-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-(trans-4-tert-butylcyclohexyl)methyl-3-hydroxynaphtho-1,4-quinone
• 英文别名: 3-hydroxy-2-(trans-4-tert-butylcyclohexyl)methylnaphtho-1,4-quinone；buparvaquone
• CAS: 86790-15-0
• 化学式: C₂₁H₂₆O₃
• 分子量: 326.436
• InChiKey: KLLIVCPQDTYMLC-HDJSIYSDSA-N

物化性质

• 熔点：
  193-201 °C
• 沸点：
  460.7±45.0 °C(Predicted)
• 密度：
  1.158±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.12
• 重原子数：
  24.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  54.37
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2-(trans-4-tert-butylcyclohexyl)methyl-3-hydroxynaphtho-1,4-quinone 在 盐酸羟胺 、 sodium acetate 、 potassium carbonate 作用下， 以 乙醇 、 水 、 丙酮 为溶剂， 反应 76.0h， 生成 (Z)-3-(trans-4-tert-butyl-cyclohexylmethyl)-2-methoxy[1,4]naphthoquinone-1-oxime
  参考文献：
  名称：

  Synthesis and antileishmanial activity of novel buparvaquone oxime derivatives

  摘要：

  Novel oxime derivatives (2, 3 and 5) of buparvaquone (1) and O-methyl-buparvaquone (4) were synthesized and their in vitro activities against Leishmania donovani, the causative agent of visceral leishmaniasis (VL), were determined. Buparvaquone-oxime (2) was also studied as a bioreversible prodrug structure of buparvaquone (1). Buparvaquone-oxime (2) released buparvaquone (1) in vitro when it was incubated with induced rat liver microsomes, which suggests that the oxime-structure is a useful prodrug template for developing novel prodrugs of buparvaquone and other hydroxynaphthoquinones. Moreover, the formation of NO2-, formed via oxidation of NO, was confirmed during the bioconversion. The release of NO from buparvaquone-oxime (2) may provide an additional therapeutic effect in the treatment of leishmaniasis. Buparvaquone-oxime (2) and buparvaquone-O-methyloxime (3) demonstrated moderate activity against amastigotes of the Leishmania species that causes VL. However, the studied oximes (2, 3) most probably did not release buparvaquone (1) and NO during the present in vitro experiment. Further in vivo studies are needed to verify the biological activity of buparvaquone-oximes in the treatment of leishmaniasis. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.04.032
• 作为产物：
  描述：

  2-氯-1,4-萘醌 在 ammonium persulfate 、 silver nitrate 作用下， 生成 2-(trans-4-tert-butylcyclohexyl)methyl-3-hydroxynaphtho-1,4-quinone
  参考文献：
  名称：

  Hudson; Pether; Randall, European Journal of Medicinal Chemistry, 1986, vol. 21, # 4, p. 271 - 275

  摘要：

  DOI：

文献信息

• Kinetics and mechanism of the hydrogen peroxide oxidation of a pentafluorophenyl-substituted iron(III) porphyrin †
  作者：Ian D. Cunningham、Timothy N. Danks、Keith T. A. O’Connell、Peter W. Scott

  DOI：10.1039/a903511g

  日期：——

  Kinetic analysis of the (F20TPP)FeCl-catalysed H2O2 oxidation of 3-hydroxy-2-(trans-4-tert-butylcyclohexyl)methylnaphtho-1,4-quinone is consistent with rapid reaction of the organic substrate with an oxoperferryl intermediate [(F20TPP˙+)FeIVO] formed in the first and rate-limiting step. A second-order rate constant for oxidation of the catalyst of 22 ± 5 dm3 mol–1 s–1 is found, a value lower than previously

  （F 20 TPP）FeCl催化的3-羟基-2-（反式-4-叔丁基环己基）甲基萘-1,4-醌的H 2 O 2氧化动力学分析与有机底物与一个oxoperferryl中间体[（F 20 TPP ˙+ ）的Fe IV形成O]在第一和限速步骤。发现催化剂氧化的二级速率常数为22±5 dm 3 mol –1 s –1，该值比以前报道的要低。在没有有机底物的情况下，H 2 O 2氧化载污催化剂到oxoferryl物种（F 20 TPP）的Fe IV O，可能经由所述oxoperferryl物种。该草酰氧化合物本身被H 2 O 2漂白，其二级速率常数为0.081±0.004 dm 3 mol –1 s –1，可能涉及卟啉环的氧化。
• 1.4-Naphthoquinones, methods for their preparation and veterinary formulations thereof
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0077550A2

  公开（公告）日：1983-04-27

  1,4-Naphthoquinones of formula (I), methods for their preparation veterinary formulations thereof, and the use thereof in animal therapy are disclosed. Particularly preferred compounds of formula (I) are, 2-[trans-(4-t-butylcyclohexyl)methyl]-3-hydroxy-1,4-naphthoquinone, and 2-[trans-(4-t-pentyl cyclohexyl)-methyl]-3-hydroxy-1,4-naphthoquinone. The compounds are of value as anti-protozoal agents, in particular as anti-theilerial agents.

  本发明公开了式 (I) 的 1,4-萘醌、其兽药制剂的制备方法及其在动物治疗中的用途。 特别优选的式 (I) 化合物有：2-[反式-(4-t-丁基环己基)甲基]-3-羟基-1,4-萘醌和 2-[反式-(4-t-戊基环己基)甲基]-3-羟基-1,4-萘醌。这些化合物具有抗原生动物药剂的价值，尤其是抗热病菌药剂。
• Synthesis, in Vitro Evaluation, and Antileishmanial Activity of Water-Soluble Prodrugs of Buparvaquone
  作者：Antti Mäntylä、Tracy Garnier、Jarkko Rautio、Tapio Nevalainen、Jouko Vepsälainen、Ari Koskinen、Simon L. Croft、Tomi Järvinen

  DOI：10.1021/jm030868a

  日期：2004.1.1

  Water-soluble phosphate prodrugs, of buparvaquone (1), containing a hydroxynaphthoquinone structure, were synthesized and evaluated in vitro for improved topical and oral drug delivery against cutaneous and visceral leishmaniasis. The successfull prodrug synthesis involved a strong base; e.g., sodium hydride. Buparvaquone-3-phosphate (4a) and 3-phosphonooxymethylbuparvaquone (4b) prodrugs possessed significantly higher aqueous solubilities (> 3.5 mg/mL) than the parent drug (less than or equal to0.03 mug/mL) over a pH range of 3.0-7.4. Moreover, 4a and 4b maintained adequate lipophilicity as indicated by distribution coefficients (log D) between 0.5 and 3.0 over this pH range. Both 4a and 4b were also shown to be substrates for alkaline phosphatase in vitro and thus are promising bioreversible prodrugs for the improved topical and oral bioavailability of 1. Buparvaquone and its prodrugs showed nanomolar or low-micromolar ED50 activity values against species that cause cutaneous leishmaniasis, e.g., L. major, L. amazonensis, L. aethiopica, L. mexicana, and L. panamensis and also L. donovani, which is the causative agent of visceral leishmaniasis. From these results, the human skin permeation of the prodrugs 4a and 4b were studied in vitro. While no buparvaquone permeated across post mortem skin in vitro during 72 h of experiments, both prodrugs 4a and 4b permeated readily through the skin. In addition, 4b easily released the parent drug in human skin homogenate and, therefore, is a promising prodrug candidate to deliver buparvaquone through the skin for the treatment of cutaneous leishmaniasis.
• Metalloporphyrin-Catalyzed Oxidation of 2-Cycloalkyl-3-hydroxynaphthoquinones
  作者：Ian D. Cunningham、Timothy N. Danks、Keith T. A. O'Connell、Peter W. Scott

  DOI：10.1021/jo990297n

  日期：1999.10.1

  Mild H2O2 oxidation of a small series of 2-cycloalkyl-3-hydroxynaphthoquinones catalyzed by 5,-10,15,20-tetrakis(pentafluorophenyl)-21H,23H-porphineiron(III) chloride in methanol-dichloromethane leads in each case to the isolation of a dehydro-dimer identified as a 3-cycloalkyl-3-(2-cycloalkylnaphthoquinon-3-yl)oxy-2-oxo-2,3-dihydronaphtho-1,4-quinone and in some cases to a 2-cycloalkyl-2,3-dihydroxy-1-oxoindan-3-carboxylate. The mechanism of formation of the former is rationalized in terms of nucleophilic attack of unreacted hydroxynaphthoquinone anion upon an epoxide primary oxidation product, while that of the latter is proposed to involve nucleophilic attack of solvent methanal on the same epoxide followed by rearrangement.
• 1.4-Naphthoquinones, methods for their preparation, pharmaceutical and veterinary formulations thereof
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0077551B1

  公开（公告）日：1985-06-12