methyl 3-<4-<(methoxymethylene)oxy>phenyl>-1-propanoate | 155997-94-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: methyl 3-<4-<(methoxymethylene)oxy>phenyl>-1-propanoate
• 英文别名: methyl 3-<4-(methoxymethoxy)phenyl>propionate；4-(methoxymethoxy)benzene propanoic acid methyl ester；methyl 3-(4-(methoxymethoxy)phenyl)propanoate；Methyl 3-[4-(methoxymethoxy)phenyl]propanoate
• CAS: 155997-94-7
• 化学式: C₁₂H₁₆O₄
• 分子量: 224.257
• InChiKey: YNSRFCIGGGDZRC-UHFFFAOYSA-N

物化性质

• 沸点：
  315.0±27.0 °C(Predicted)
• 密度：
  1.090±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 3-<4-<(methoxymethylene)oxy>phenyl>-1-propanoate 在 盐酸 、 4-二甲氨基吡啶 、 锂硼氢 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 42.0h， 生成 3,5-Bis-benzyloxy-4-(2-benzyloxy-6-benzyloxycarbonyl-benzoyl)-benzoic acid 3-(4-hydroxy-phenyl)-propyl ester
  参考文献：
  名称：

  Synthesis and Protein Kinase C Inhibitory Activities of Acyclic Balanol Analogs That Are Highly Selective for Protein Kinase C over Protein Kinase A

  摘要：

  A series of balanol analogs in which the perhydroazepine ring and the p-hydroxybenzamide moiety were combined into an acyclic linked unit have been prepared and evaluated for their inhibitory properties against the serine/threonine kinase PKC. Several low-micromolar to low-nanomolar inhibitors of the alpha, beta(I), beta(II), gamma, delta, epsilon, and eta PKC: isozymes were prepared. In general, these acyclic balanol analogs were found to be highly selective for PKC over the serine/threonine kinase PKA. The type and number of atoms linking the benzophenone ester to the p-hydroxyphenyl group necessary for optimal PKC inhibition were investigated. The most potent compounds contained a three-carbon linker in which the carboxamide moiety of balanol had been replaced by a methylene group. The effect of placing substituents on the three-carbon chain was also investigated. The preferred compounds contained either a 2-benzenesulfonamido (6b) or a 1-methyl (21b) substituent. The preferred compounds 6b and 21b were tested against a panel of serine/threonine kinases and found to be highly selective for PKC. The more active enantiomer of 6b, (S)-12b, was 3-10-fold more active than the R-enantiomer against the PKC isozymes. The effect of making the analogs more rigid by making the three-carbon chain part of a five-membered ring, but with retention of the methylene replacement for the carboxamide moiety, led to potent PKC inhibitors including anti-substituted pyrrolidine analog 35b and the most potent PKC inhibitor in the series, anti-substituted cyclopentane analog 29b. The anti cyclopentane analog 29b was a low-micromolar inhibitor of the PMA-induced superoxide burst in neutrophils, and its carboxylic ester was a high-nanomolar inhibitor of neutrophils. Finally esterification of 21b, (S)-12b, and 35b turned these potent PKC inhibitors into low-micromolar inhibitors of neutrophils.

  DOI：

  10.1021/jm960581w
• 作为产物：
  描述：

  对羟基苯丙酸 在 硫酸 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.5h， 生成 methyl 3-<4-<(methoxymethylene)oxy>phenyl>-1-propanoate
  参考文献：
  名称：

  从槲寄生中分离出的新药 (1E,4E)-1,7-bis(4-hydroxyphenyl)hepta-1,4-dien-3-one 用于潜在治疗各种癌症：合成、药代动力学和药效学

  摘要：

  (1 E ,4 E )-1,7-Bis(4-hydroxyphenyl)hepta-1,4-dien-3-one (DHDK) 是一种从槲寄生中分离出来的新型姜黄素类似物。DHDK 表现出比姜黄素更好的抗肿瘤活性、更高的生物利用度和优越的稳定性。DHDK很难从Viscum coloratum中分离出来，但可以合成。MTT（甲基噻唑基二苯基溴化四唑）测定用于评估合成的 DHDK 对 12 种癌细胞系的体外细胞毒活性。结果表明，DHDK 作为抗癌剂表现出极好的潜力，尤其是对于乳腺癌和肺癌。在体内进一步评估功效通过使用 MCF-7 乳腺癌模型。DHDK 表现出剂量依赖性关系，没有体重减轻、死亡率生长抑制或组织毒性。药代动力学和组织分布统计通过 LC-ESI-MS/MS 确定。这项工作提供了关于这种天然化合物的初步数据，并可以为改变相关参数以提高药物疗效开辟新的前景。

  DOI：

  10.1039/d0ra03674a

文献信息

• Protecting Group for Carboxyl Function: Mild and Facile Cleavage of 2-Cyanoethyl Ester under Non-hydrolytic Conditions.
  作者：Yasuyuki KITA、Hiroshi MAEDA、Fumie TAKAHASHI、Seiji FUKUI、Toshihisa OGAWA、Katsuo HATAYAMA

  DOI：10.1248/cpb.42.147

  日期：——

  The use of the 2-cyanoethyl group for carboxyl-protection is described. This group was readily introduced by esterification using ethylene cyanohydrin and the deprotection was carried out under mild conditions using tetrabutylammonium fluoride in dimethylformamide-tetrahydrofuran.

  介绍了如何使用 2-氰乙基进行羧基保护。该基团很容易通过乙烯氰醇的酯化作用引入，并在二甲基甲酰胺-四氢呋喃中使用四丁基氟化铵在温和的条件下进行脱保护。
• 一种合成1,7-二-（4-羟基苯基）-庚烷-1,4-二烯-3-酮的方法
  申请人：沈阳药科大学

  公开号：CN107721836A

  公开（公告）日：2018-02-23

  本发明涉及药物合成领域，涉及一种合成1,7‑二‑(4‑羟基苯基)‑庚烷‑1,4‑二烯‑3‑酮的方法。一种合成1,7‑二‑(4‑羟基苯基)‑庚烷‑1,4‑二烯‑3‑酮的方法，以3‑(4‑羟基苯基)丙酸和4‑羟基苯甲醛为原料，其步骤是：(一)3‑(4‑羟基苯基)丙酸为原料，经过酯化、甲基保护、还原、氧化得3‑(4‑(甲氧基甲基)苯基)丙醛；(二)4‑羟基苯甲醛经过醚化、羟醛缩合反应得4‑(4‑(甲氧基甲基)苯基)丁‑3‑烯‑2‑酮；(三)将4‑(4‑(甲氧基甲氧基)苯基)丁‑3‑烯‑2‑酮和3‑(4‑(甲氧基甲氧基)苯基)丙醛进行羟醛缩合，再与盐酸反应，得到1,7‑二‑(4‑羟基苯基)‑庚烷‑1,4‑二烯‑3‑酮。该方法简单，易操作，收率高，纯度高。
• Synthesis and Protein Kinase C Inhibitory Activities of Acyclic Balanol Analogs That Are Highly Selective for Protein Kinase C over Protein Kinase A
  作者：Jean M. Defauw、Marcia M. Murphy、G. Erik Jagdmann、Hong Hu、John W. Lampe、Sean P. Hollinshead、Thomas J. Mitchell、Heidi M. Crane、Julia M. Heerding、José S. Mendoza、Jefferson E. Davis、James W. Darges、Frederick R. Hubbard、Steven E. Hall

  DOI：10.1021/jm960581w

  日期：1996.1.1

  A series of balanol analogs in which the perhydroazepine ring and the p-hydroxybenzamide moiety were combined into an acyclic linked unit have been prepared and evaluated for their inhibitory properties against the serine/threonine kinase PKC. Several low-micromolar to low-nanomolar inhibitors of the alpha, beta(I), beta(II), gamma, delta, epsilon, and eta PKC: isozymes were prepared. In general, these acyclic balanol analogs were found to be highly selective for PKC over the serine/threonine kinase PKA. The type and number of atoms linking the benzophenone ester to the p-hydroxyphenyl group necessary for optimal PKC inhibition were investigated. The most potent compounds contained a three-carbon linker in which the carboxamide moiety of balanol had been replaced by a methylene group. The effect of placing substituents on the three-carbon chain was also investigated. The preferred compounds contained either a 2-benzenesulfonamido (6b) or a 1-methyl (21b) substituent. The preferred compounds 6b and 21b were tested against a panel of serine/threonine kinases and found to be highly selective for PKC. The more active enantiomer of 6b, (S)-12b, was 3-10-fold more active than the R-enantiomer against the PKC isozymes. The effect of making the analogs more rigid by making the three-carbon chain part of a five-membered ring, but with retention of the methylene replacement for the carboxamide moiety, led to potent PKC inhibitors including anti-substituted pyrrolidine analog 35b and the most potent PKC inhibitor in the series, anti-substituted cyclopentane analog 29b. The anti cyclopentane analog 29b was a low-micromolar inhibitor of the PMA-induced superoxide burst in neutrophils, and its carboxylic ester was a high-nanomolar inhibitor of neutrophils. Finally esterification of 21b, (S)-12b, and 35b turned these potent PKC inhibitors into low-micromolar inhibitors of neutrophils.
• Novel drug isolated from mistletoe (1<i>E</i>,4<i>E</i>)-1,7-bis(4-hydroxyphenyl)hepta-1,4-dien-3-one for potential treatment of various cancers: synthesis, pharmacokinetics and pharmacodynamics
  作者：Jing Hong、Lin Meng、Peipei Yu、Ceng Zhou、Zhaoyan Zhang、Zhiguo Yu、Feng Qin、Yunli Zhao

  DOI：10.1039/d0ra03674a

  日期：——

  4-dien-3-one (DHDK) is a novel curcuminoid analogue isolated from mistletoe. DHDK exhibits better anti-tumour activity, higher bioavailability and superior stability than curcumin. DHDK is difficult to isolate from Viscum coloratum, but it can be synthesised. MTT (methylthiazolyldiphenyl tetrazolium bromide) assay was used to evaluate the in vitro cytotoxic activity of synthesised DHDK on 12 cancer

  (1 E ,4 E )-1,7-Bis(4-hydroxyphenyl)hepta-1,4-dien-3-one (DHDK) 是一种从槲寄生中分离出来的新型姜黄素类似物。DHDK 表现出比姜黄素更好的抗肿瘤活性、更高的生物利用度和优越的稳定性。DHDK很难从Viscum coloratum中分离出来，但可以合成。MTT（甲基噻唑基二苯基溴化四唑）测定用于评估合成的 DHDK 对 12 种癌细胞系的体外细胞毒活性。结果表明，DHDK 作为抗癌剂表现出极好的潜力，尤其是对于乳腺癌和肺癌。在体内进一步评估功效通过使用 MCF-7 乳腺癌模型。DHDK 表现出剂量依赖性关系，没有体重减轻、死亡率生长抑制或组织毒性。药代动力学和组织分布统计通过 LC-ESI-MS/MS 确定。这项工作提供了关于这种天然化合物的初步数据，并可以为改变相关参数以提高药物疗效开辟新的前景。