苯甲醇,a-(3-羟基-4-甲氧苯基)-3,4,5-三甲氧基- | 138958-69-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 苯甲醇,a-(3-羟基-4-甲氧苯基)-3,4,5-三甲氧基-
• 英文名称: 5-[hydroxy(3,4,5-trimethoxyphenyl)methyl]-2-methoxyphenol
• CAS: 138958-69-7
• 化学式: C₁₇H₂₀O₆
• 分子量: 320.342
• InChiKey: WXRDVGDJKAQJJA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.51
• 重原子数：
  23.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  77.38
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  苯甲醇,a-(3-羟基-4-甲氧苯基)-3,4,5-三甲氧基- 在 二氯二甲基硅烷 、 sodium iodide 作用下， 以 甲醚 、 二氯甲烷 为溶剂， 反应 0.17h， 以34%的产率得到2-Methoxy-5-(3,4,5-trimethoxy-benzyl)-phenol
  参考文献：
  名称：

  Synthesis of alkoxy-substituted diaryl compounds and correlation of ring separation with inhibition of tubulin polymerization: differential enhancement of inhibitory effects under suboptimal polymerization reaction conditions

  摘要：

  A number of cytostatic compounds (2-4, 7, and 8), which can be described as ''diaryl'', inhibit tubulin polymerization, cause cells to accumulate in mitotic arrest, and competitively inhibit the binding of colchicine to tubulin. They differ, however, in the separation of the two aryl moieties. To attempt to understand this variability we prepared a series of analogues modeled on 3 and 4 (''benzodioxole series'') and on 7 and 8 (''combretastatin series'') which differed only in the number of methylene units (ranging from none to four) separating the aryl moieties. These compounds were evaluated for their effects on tubulin polymerization, colchicine binding, and the growth of L1210 murine leukemia cells. In terms of inhibitory effects on tubulin polymerization, for the combretastatin series there was an optimal separation of the two phenyl rings by a two-carbon bridge (compound 24), with progressively decreasing inhibitory activity when the separation was by one carbon (20), three carbons (25), or four carbons (28) (the biphenyl analogue 16 was inactive). The benzodioxole series, however, did not permit us to generalize this finding, because the least active agents prepared (39 and 40) had a two-carbon bridge, while those with one- (5 and 6) and three-carbon (46 and 47) bridges were nearly equivalent in potency. Submicromolar IC50 values for inhibition of L1210 cell growth were only obtained for compounds 20 (IC50, 0.2-mu-M), 24 (0.07-mu-M), and 25 (0.4-mu-M). While evaluating the effects of these agents on tubulin polymerization, we noted with the combretastatin series and with several standard agents that apparent potency (in terms of IC50 values) was always lower if the reaction was performed at 30-degrees-C, with 0.25 mM MgCl2, than at 37-degrees-C, with 1.0 mM MgCl2. This enhancement of IC50 values in the former system as compared with the latter was particularly dramatic for the less active agents (e.g., 28) as compared with the more active (e.g. 24).

  DOI：

  10.1021/jm00084a011
• 作为产物：
  描述：

  phenstatin 在 sodium tetrahydroborate 作用下， 以 乙醇 、 水 为溶剂， 反应 4.0h， 以97%的产率得到苯甲醇,a-(3-羟基-4-甲氧苯基)-3,4,5-三甲氧基-
  参考文献：
  名称：

  超临界流体色谱法用于可持续生产新型立体异构抗癌剂。

  摘要：

  描述了两种旨在制造史无前例的立体异构体康他汀A-4类似物的途径：快速色谱与超临界流体色谱。后者比液相色谱法具有许多优势，因此被选择用于小规模分离1-[（3-羟基-4-甲氧基苯基）（3,4,5-三甲氧基苯基）甲基] -5-氧-1-脯氨酸甲酯5，具有潜在的抗肿瘤活性。在筛选了六个不同的基于多糖的手性固定相和四种助溶剂后，通过实验设计（DoE）优化了助溶剂的百分比，流速和出口压力。在Chiralpak AD-H上以异丙醇为助溶剂成功制备了50 mg的每种立体异构体。计算了生产率（kkd），溶剂用量和环境因子（E因子）。

  DOI：

  10.1016/j.jpba.2017.08.006

文献信息

• Synthesis and biological evaluation of phenstatin metabolites
  作者：Alina Ghinet、Benoît Rigo、Jean-Pierre Hénichart、Delphine Le Broc-Ryckewaert、Jean Pommery、Nicole Pommery、Xavier Thuru、Bruno Quesnel、Philippe Gautret

  DOI：10.1016/j.bmc.2011.08.047

  日期：2011.10

  metabolites. The structures of eight of these metabolites have been now confirmed by synthesis and their biological properties have been reported. Eaton’s reagent was utilized as a convenient condensing agent, allowing, among others, a simple multigram scale preparation of phenstatin. Synthesized metabolites and related compounds were evaluated for their antiproliferative activity in the NCI-60 cancer cell

  以前对非那他汀与大鼠和人类微粒体组分温育的研究表明形成了九种主要代谢产物。现在已经通过合成确认了其中8种代谢物的结构，并报道了它们的生物学特性。伊顿的试剂被用作便利的缩合剂，除其他外，还可以简单地制得数克规模的芬他汀。评价了合成代谢产物和相关化合物在NCI-60癌细胞系中的抗增殖活性，以及​​它们对微管组装的影响。代谢物23（2'-甲氧吩他汀）表现出最有效的体外细胞毒性活性：抑制K-562，NCI-H322M，NCI-H522，KM12，M14，MDA-MB-435，NCI / ADR-RES，和带有GI的HS 578T细胞系50个值<10 nM。它也显示出比亲本芬他汀（3）更显着的微管蛋白聚合抑制活性（IC 50  = 3.2μM对15.0μM ），并在鼠白血病DA1-3b细胞中诱导G2 / M阻滞。对这种活性代谢产物的鉴定导致了具有强大的体外细胞毒性和抑制微管组装的类似物的设计和合成。
• Synthesis and Biological Evaluation of 1-(Diarylmethyl)-1H-1,2,4-triazoles and 1-(Diarylmethyl)-1H-imidazoles as a Novel Class of Anti-Mitotic Agent for Activity in Breast Cancer
  作者：Gloria Ana、Patrick M. Kelly、Azizah M. Malebari、Sara Noorani、Seema M. Nathwani、Brendan Twamley、Darren Fayne、Niamh M. O’Boyle、Daniela M. Zisterer、Elisangela Flavia Pimentel、Denise Coutinho Endringer、Mary J. Meegan

  DOI：10.3390/ph14020169

  日期：——

  We report the synthesis and biochemical evaluation of compounds that are designed as hybrids of the microtubule targeting benzophenone phenstatin and the aromatase inhibitor letrozole. A preliminary screening in estrogen receptor (ER)-positive MCF-7 breast cancer cells identified 5-((2H-1,2,3-triazol-1-yl)(3,4,5-trimethoxyphenyl)methyl)-2-methoxyphenol 24 as a potent antiproliferative compound with

  我们报告了化合物的合成和生化评估，这些化合物被设计为靶向二苯甲酮芬司他汀和芳香酶抑制剂来曲唑的微管杂合体。对雌激素受体 (ER) 阳性 MCF-7 乳腺癌细胞的初步筛选鉴定出 5-((2 H -1,2,3-三唑-1-基)(3,4,5-三甲氧基苯基)甲基)-2 -甲氧基苯酚24作为一种有效的抗增殖化合物，在 MCF-7 乳腺癌细胞 (ER+/​​PR+) 中的 IC 50值为 52 nM，在三阴性 MDA-MB-231 乳腺癌细胞中的 IC 50 值为 74 nM。这些化合物在 MCF-7 细胞系中表现出显着的 G 2 /M 期细胞周期停滞和诱导细胞凋亡，抑制微管蛋白聚合，并且在非致瘤性 MCF-10A 乳腺细胞中进行评估时对癌细胞具有选择性。 MCF-7 细胞的免疫荧光染色证实，这些化合物靶向微管蛋白并诱导多核，这是有丝分裂灾难的公认标志。微管蛋白秋水仙碱结合位点中化合物19e 、 21l
• Supercritical fluid chromatography approach for a sustainable manufacture of new stereoisomeric anticancer agent
  作者：Alina Ghinet、Yasmine Zehani、Emmanuelle Lipka

  DOI：10.1016/j.jpba.2017.08.006

  日期：2017.10

  Two routes aimed at the manufacture of unprecedented stereoisomeric combretastatin A-4 analogue were described: flash chromatography vs supercritical fluid chromatography. The latter has many advantages over liquid chromatography and was therefore chosen for the small scale separation of methyl 1-[(3-hydroxy-4-methoxyphenyl) (3,4,5-trimethoxyphenyl)methyl]-5-oxo-l-prolinate 5, with potential antitumoral

  描述了两种旨在制造史无前例的立体异构体康他汀A-4类似物的途径：快速色谱与超临界流体色谱。后者比液相色谱法具有许多优势，因此被选择用于小规模分离1-[（3-羟基-4-甲氧基苯基）（3,4,5-三甲氧基苯基）甲基] -5-氧-1-脯氨酸甲酯5，具有潜在的抗肿瘤活性。在筛选了六个不同的基于多糖的手性固定相和四种助溶剂后，通过实验设计（DoE）优化了助溶剂的百分比，流速和出口压力。在Chiralpak AD-H上以异丙醇为助溶剂成功制备了50 mg的每种立体异构体。计算了生产率（kkd），溶剂用量和环境因子（E因子）。
• Synthesis of alkoxy-substituted diaryl compounds and correlation of ring separation with inhibition of tubulin polymerization: differential enhancement of inhibitory effects under suboptimal polymerization reaction conditions
  作者：Zelleka Getahun、Leonard Jurd、Ping S. Chu、Chii M. Lin、Ernest Hamel

  DOI：10.1021/jm00084a011

  日期：1992.3

  A number of cytostatic compounds (2-4, 7, and 8), which can be described as ''diaryl'', inhibit tubulin polymerization, cause cells to accumulate in mitotic arrest, and competitively inhibit the binding of colchicine to tubulin. They differ, however, in the separation of the two aryl moieties. To attempt to understand this variability we prepared a series of analogues modeled on 3 and 4 (''benzodioxole series'') and on 7 and 8 (''combretastatin series'') which differed only in the number of methylene units (ranging from none to four) separating the aryl moieties. These compounds were evaluated for their effects on tubulin polymerization, colchicine binding, and the growth of L1210 murine leukemia cells. In terms of inhibitory effects on tubulin polymerization, for the combretastatin series there was an optimal separation of the two phenyl rings by a two-carbon bridge (compound 24), with progressively decreasing inhibitory activity when the separation was by one carbon (20), three carbons (25), or four carbons (28) (the biphenyl analogue 16 was inactive). The benzodioxole series, however, did not permit us to generalize this finding, because the least active agents prepared (39 and 40) had a two-carbon bridge, while those with one- (5 and 6) and three-carbon (46 and 47) bridges were nearly equivalent in potency. Submicromolar IC50 values for inhibition of L1210 cell growth were only obtained for compounds 20 (IC50, 0.2-mu-M), 24 (0.07-mu-M), and 25 (0.4-mu-M). While evaluating the effects of these agents on tubulin polymerization, we noted with the combretastatin series and with several standard agents that apparent potency (in terms of IC50 values) was always lower if the reaction was performed at 30-degrees-C, with 0.25 mM MgCl2, than at 37-degrees-C, with 1.0 mM MgCl2. This enhancement of IC50 values in the former system as compared with the latter was particularly dramatic for the less active agents (e.g., 28) as compared with the more active (e.g. 24).