佛波醇13-乙酸酯 | 32752-29-7

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 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
• 中文名称: 佛波醇13-乙酸酯
• 中文别名: 13-乙酸佛波醇；佛波醇 13-乙酸酯
• 英文名称: Phorbol-13-acetate
• 英文别名: 13-Acetylphorbol；[(1S,2S,6R,10S,11R,13S,14R,15R)-1,6,14-trihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-13-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] acetate
• CAS: 32752-29-7
• 化学式: C₂₂H₃₀O₇
• mdl: MFCD00056375
• 分子量: 406.476
• InChiKey: SDSVJYOOAPRSDA-RPCQODIISA-N

物化性质

• 沸点：
  582.4±50.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)
• 稳定性/保质期：
  遵照规定使用和储存，则不会分解。

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.727
• 拓扑面积：
  124
• 氢给体数：
  4
• 氢受体数：
  7

安全信息

• 危险品标志：
  T+
• 危险类别码：
  R26/27/28
• 安全说明：
  S26,S27,S36,S37,S39,S45

反应信息

• 作为产物：
  描述：

  Phorbol 13,20-diacetate 在 高氯酸 作用下， 以 甲醇 为溶剂， 生成 佛波醇13-乙酸酯
  参考文献：
  名称：

  Differential effects of phorbol-13-monoesters on human immunodeficiency virus reactivation

  摘要：

  The persistence of latent reservoirs of HIV-1 represents a major barrier to virus eradication in patients treated with antiretrovirals. Prostratin is a non-tumor promoting 12-deoxyphorbol monoester capable of up-regulating viral expression from latent provirus and therefore is potentially useful for HIV adjuvant therapy and similar properties might be elicited by related non-tumor promoting phorboids. We have therefore investigated a series of phorbol 13-monoesters for their capacity to reactivate HIV latency. Using a Jurkat T cell line containing latent HIV proviruses, we found that prostratin and phorbol-13-stearate effectively activate HIV-1 gene expression in these latently infected cells, with phorbol-13-stearate being at least 10-fold more potent than prostratin, and its activity rapidly decreasing with a shortening of the acyl side chain. We further demonstrated that phorbol-13-stearate and prostratin stimulate IKK-dependent phosphorylation and degradation of I kappa B alpha, leading to activation of NF-kappa B. Moreover, prostratin, phorbol-13-hexanoate and phorbol-13-stearate also activate the JNK and ERK pathways. Studies with isoform-specific PKC inhibitors suggest that the classical PKCs play a prominent role in the responses elicited by phorbol-13-stearate. Nevertheless, this compound induces a translocation pattern of the PKC isotypes alpha and delta to cellular compartments distinctly different from that elicited by prostratin and PMA. (c) 2007 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2007.12.004

文献信息

• Compositions containing aromatic aldehydes and their use in treatments
  申请人：——

  公开号：US20030124157A1

  公开（公告）日：2003-07-03

  Disclosed are pharmaceutical and cosmetic compositions containing aromatic aldehyde compounds. Some of the disclosed compositions are useful as topical therapeutics for treating inflammatory dermatologic conditions. Some of the compositions are useful in transdermal and other systemic dose forms for treating other inflammatory conditions in mammals.

  揭示了含有芳香醛类化合物的药用和化妆品组合物。其中一些组合物可用作治疗炎症性皮肤病的局部治疗药物。其中一些组合物可用于治疗哺乳动物体内其他炎症性疾病的经皮和其他系统剂型。
• Inhibition of Cytopathic Effect of Human Immunodeficiency Virus Type-1 by Various Phorbol Derivatives.
  作者：Sahar El-Mekkawy、Meselhy Ragab Meselhy、Atef Abdel-Monem Abdel-Hafez、Norio Nakamura、Masao Hattori、Takuya Kawahata、Toru Otake

  DOI：10.1248/cpb.50.523

  日期：——

  Forty-eight derivatives of phorbol (9) and isophorbol (14) were evaluated for their inhibition of human immunodeficiency virus (HIV)-1 induced cytopathic effects (CPE) on MT-4 cells, as well as their activation of protein kinase C (PKC), as indices of anti-HIV-1 and tumor promoting activities, respectively. Of these compounds, the most potent inhibition of CPE was observed in 12-O-tetradecanoylphorbol 13-acetate (8) and 12-O-acetylphorbol 13-decanoate (6). The former also showed the strongest PKC activation activity, while the latter showed no activity at 10 ng/ml. Both activities were generally observed in those phorbol derivatives with an A/B trans configuration, but not in the isophorbol derivatives with an A/B cis configuration. Acetylation of 20-OH in the phorbol derivatives significantly reduced the inhibition of CPE, as shown in 12-O-, 20-O-diacetylphorbol 13-decanoate (6a) (IC100=15.6 μg/ml) vs. compound 6 (IC100=0.0076 μg/ml), and 12-O-tetradecanoylphorbol 13,20-diacetate (8a) (IC100=15.6 μg/ml) vs. 12-O-tetradecanoylphorbol 13-acetate (8) (IC100=0.00048 μg/ml), except in the case of 12-O-decanoylphorbol 13-(2-methylbutyrate) (4) and phorbol 12,13-diacetate (9c). The reduction of a carbonyl group at C-3 abruptly reduced the inhibition of CPE, as observed in 3β-hydroxyphorbol 12,13,20-triacetate (9f) (IC100=500 μg/ml) vs. phorbol 12,13,20-triacetate (9d) (IC100=62.5 μg/ml). Although 8 was equipotent in the inhibition of CPE, and activation of PKC, both activities were abruptly decreased by the acetylation of 20-OH and methylation of 4-OH [as in 8a and 4-O-methyl-12-O-tetradecanoylphorbol 13,20-diacetate (8b), respectively]. On the other hand, its positional isomer (12-O-acetylphorbol 13-tetradecanoate (8c) showed neither activities. The removal of a long acyl group in 8 led to a substantial loss of both activities, as shown in phorbol 13-acetate (9b). Of the 12-O-acetyl-13-O-acylphorbol derivatives, the highest inhibition of CPE was observed in 6, which has a dodecanoyl residue at C-13. Both an increase and decrease in the number of fatty acid carbon chains resulted in significant reduction of the inhibition of CPE.

  四十八种分子的phorbol（9）和isophorbol（14）被评估其对人类免疫缺陷病毒（HIV）-1诱导的细胞病变效应（CPE）在MT-4细胞上的抑制作用，以及其激活蛋白激酶C（PKC）的能力，分别作为抗HIV-1和肿瘤促进活性的指标。在这些化合物中，12-O-十四酸酯phorbol 13-醋酸酯（8）和12-O-乙酰phorbol 13-癸酸酯（6）显示出对CPE的最强抑制作用。前者也表现出最强的PKC激活活性，而后者在10 ng/ml时未显示活性。这两种活性通常是在具有A/B反式构型的phorbol衍生物中观察到的，而不是在具有A/B顺式构型的isophorbol衍生物中。对phorbol衍生物中的20-OH进行乙酰化显著降低了对CPE的抑制，正如在12-O-、20-O-二乙酰phorbol 13-癸酸酯（6a）（IC100=15.6 μg/ml）与化合物6（IC100=0.0076 μg/ml）之间的对比，以及在12-O-十四酸酯phorbol 13,20-二乙酸酯（8a）（IC100=15.6 μg/ml）与12-O-十四酸酯phorbol 13-醋酸酯（8）（IC100=0.00048 μg/ml）之间的对比，除了在12-O-癸酸酯phorbol 13-(2-甲基丁酸酯)（4）和phorbol 12,13-二乙酸酯（9c）情况下。C-3碳基团的去除突然降低了对CPE的抑制，正如在3β-羟基phorbol 12,13,20-三乙酸酯（9f）（IC100=500 μg/ml）与phorbol 12,13,20-三乙酸酯（9d）（IC100=62.5 μg/ml）之间的对比所观察到的。尽管8在抑制CPE和激活PKC方面具有同等效力，但20-OH的乙酰化和4-OH的甲基化（如在8a和4-O-甲基-12-O-十四酸酯phorbol 13,20-二乙酸酯（8b）中）都急剧降低了这两种活性。另一方面，其位置异构体（12-O-乙酰phorbol 13-十四酸酯（8c）则表现出两种活性均无）。在8中去除长的酰基团导致这两种活性的显著丧失，如在phorbol 13-醋酸酯（9b）中所示。在12-O-乙酰-13-O-酰基phorbol衍生物中，6显示出对CPE的最高抑制，C-13处具有十二酸酯残基。脂肪酸碳链数量的增加和减少均导致对CPE抑制作用的显著降低。
• Rigid pyrrolidone modulators of pkc
  申请人：——

  公开号：US20040019018A1

  公开（公告）日：2004-01-29

  Compounds of the general formula (I): wherein substituents at R 1 , R 2 , R 3 and R 4 have any of the values defined in the specification, and their pharmaceutically acceptable salts, are PKC modulators and are useful for treating diseases, such as, for example, cancers including prostate cancer, inflammatory, autoimmune and neurological disorders including Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising compounds of formula (I), processes for preparing compounds of formula (I), and intermediates useful for preparing compounds of formula (I).

  通式（I）的化合物：其中R1、R2、R3和R4的取代基具有规范中定义的任何值，以及它们的药学上可接受的盐，是PKC调节剂，可用于治疗疾病，例如癌症（包括前列腺癌）、炎症、自身免疫和神经系统疾病（包括阿尔茨海默病）。还公开了包括通式（I）化合物的制药组合物、制备通式（I）化合物的方法，以及制备通式（I）化合物有用的中间体。
• [EN] DISUBSTITUTED ACETYLENES BEARING HETEROAROMATIC AND HETEROBICYCLIC GROUPS HAVING RETINOID-LIKE ACTIVITY<br/>[FR] ACETYLENES DISUBSTITUES A GROUPES HETEROAROMATIQUES ET HETEROBICYCLIQUES PRESENTANT UNE ACTIVITE DE TYPE RETINOIDE
  申请人：ALLERGAN

  公开号：WO1996011686A1

  公开（公告）日：1996-04-25

  (EN) Retinoid-like activity is exhibited by compounds of formula (I) where X is S, O, or NR' where R' is hydrogen or lower alkyl; R is hydrogen or lower alkyl; A is pyridyl, thienyl, furyl, pyridazinyl, pyrimidinyl or pyrazinyl; n is 0-4; and B is H, -COOH or a pharmaceutically acceptable salt, ester or amide thereof, -CH2OH or an ether or ester derivative, or -CHO or an acetal derivative, or -COR1 or a ketal derivative where R1 is -(CH2)mCH3 where m is 0-4, or a pharmaceutically acceptable salt thereof.(FR) Selon la présente invention, des composés de la formule générale (I) font preuve d'une activité de type rétinoïde. Dans cette formule générale, X est S, O ou NR', R' étant hydrogène ou alklye inférieur; R est hydrogène ou alkyle inférieur; A est pyridyle, thiényle, furyle, pyridazinyle, pyrimidinyle ou pyrazinyle; n est un entier de 0 à 4; et B est H, -COOH ou l'un de ses sels, esters ou amides acceptables du point de vue pharmaceutique, -CH2OH ou un dérivé éther ou ester, ou -CHO ou un dérivé acétal, ou -COR1 ou un dérivé cétal dans lequel R1 est -(CH2)mCH3, m étant un entier de 0 à 4, ou l'un de leurs sels acceptables du point de vue pharmaceutique.

  化合物的通式（I）中，具有类视视黄醇活性，其中X为S、O或NR'，其中R'为氢或低碳基；R为氢或低碳基；A为吡啶基、噻吩基、呋喃基、吡嗪基、嘧啶基或吡咯基；n为0-4；B为H、-COOH或其药学上可接受的盐、酯或酰胺，-CH2OH或其醚或酯衍生物，或-CHO或其缩醛衍生物，或-COR1或其缩酮衍生物，其中R1为-(CH2)mCH3，m为0-4，或其药学上可接受的盐。
• Ester Prodrugs of Prostratin and Related Phorbol Compounds
  申请人：Xu Rensheng

  公开号：US20110251421A1

  公开（公告）日：2011-10-13

  The present disclosure provides analogs and derivatives of phorbol compounds for the treatment of viral infections, neoplastic diseases, inflammatory reactions, and use as analgesics.

  本公开提供了类似于并生物衍生物的茂丙烷化合物，用于治疗病毒感染、肿瘤性疾病、炎症反应，并用作镇痛剂。