4-(3-phenoxy) propoxybenzaldehyde

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-(3-phenoxy) propoxybenzaldehyde
• 英文别名: 4-(3-Phenoxypropoxy)benzaldehyde
• 化学式: C₁₆H₁₆O₃
• mdl: MFCD13874117
• 分子量: 256.301
• InChiKey: ODNNCZJWIMATES-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.187
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-吗啉基)丙腈 、 4-(3-phenoxy) propoxybenzaldehyde 在 sodium methylate 作用下， 以 二甲基亚砜 为溶剂， 生成
  参考文献：
  名称：

  Target Guided Synthesis of 5-Benzyl-2,4-diamonopyrimidines: Their Antimalarial Activities and Binding Affinities to Wild Type and Mutant Dihydrofolate Reductases from Plasmodium falciparum

  摘要：

  The resistance to pyrimethamine (PYR) of Plasmodium falciparum arising from mutation at position 108 of dihydrofolate reductase (pfDHFR) from serine to asparagine (S108N) is due to steric interaction between the bulky side chain of N108 and Cl atom of the 5-p-Cl aryl group of PYR, which consequently resulted in the reduction in binding affinity between the enzyme and inhibitor. Molecular modeling suggested that the flexible antifolate, such as trimethoprim (TMP) derivatives, could avoid this steric constraint and should be considered as new, potentially effective compounds. The hydrophobic interaction between the side chain of inhibitor and the active site of the enzyme around position 108 was enhanced by the introduction of a longer and more hydrophobic side chain on TMP's 5-benzyl moiety. The prepared compounds, especially those bearing aromatic substituents, exhibited better binding affinities to both wild type and mutant enzymes than the parent compound. Binding affinities of these compounds correlated well with their antimalarial. activities against both wild type and resistant parasites. Molecular modeling of the binding of such compounds with pfDHFR also supported the experimental data and clearly showed that aromatic substituents play an important role in enhancing binding affinity. In addition, some compounds with 6-alkyl substituents showed relatively less decrease in binding constants with the mutant enzymes and relatively good antimalarial. activities against the parasites bearing the mutant enzymes.

  DOI：

  10.1021/jm0303352
• 作为产物：
  描述：

  对羟基苯甲醛 、 3-苯氧基溴丙烷 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以95 %的产率得到4-(3-phenoxy) propoxybenzaldehyde
  参考文献：
  名称：

  设计用于治疗 2 型糖尿病及其并发症的多种配体：发现作为新型双靶点 PTP1B/AKR1B1 抑制剂具有活性的 (5-arylidene-4-oxo-2-thioxothiazolidin-3-yl)alkanoic acids

  摘要：

  2 型糖尿病 (T2DM) 是一种严重的慢性疾病，其全球患病率正以惊人的速度增长。目前 T2DM 的治疗主要依靠药物组合来控制血糖水平，从而预防高血糖相关并发症的发生。多靶点药物的开发最近成为药物组合的有吸引力的替代品，用于治疗具有多因素发病机制的复杂疾病，例如 T2DM。蛋白酪氨酸磷酸酶 1B (PTP1B) 和醛糖还原酶 (AKR1B1) 是与 T2DM 及其慢性并发症的发展密切相关的两种酶，因此，针对这两种酶的双重抑制剂可以为治疗这种复杂的病理状况提供新的药物. 在继续寻找双靶点 PTP1B/AKR1B1 抑制剂的过程中，我们设计了新的 (5-arylidene-4-oxo-2-thioxothiazolidin-3-yl) 链烷酸。其中，3-(4-苯基丁氧基)亚苄基衍生物6f和7f具有针对两个靶标的有趣抑制活性，证明可以控制与 T2DM 和相关并发症的发展有关的特定细胞通路。

  DOI：

  10.1016/j.ejmech.2023.115270

文献信息

• Target Guided Synthesis of 5-Benzyl-2,4-diamonopyrimidines: Their Antimalarial Activities and Binding Affinities to Wild Type and Mutant Dihydrofolate Reductases from <i>Plasmodium falciparum</i>
  作者：Chawanee Sirichaiwat、Chakapong Intaraudom、Sumalee Kamchonwongpaisan、Jarunee Vanichtanankul、Yodhathai Thebtaranonth、Yongyuth Yuthavong

  DOI：10.1021/jm0303352

  日期：2004.1.1

  The resistance to pyrimethamine (PYR) of Plasmodium falciparum arising from mutation at position 108 of dihydrofolate reductase (pfDHFR) from serine to asparagine (S108N) is due to steric interaction between the bulky side chain of N108 and Cl atom of the 5-p-Cl aryl group of PYR, which consequently resulted in the reduction in binding affinity between the enzyme and inhibitor. Molecular modeling suggested that the flexible antifolate, such as trimethoprim (TMP) derivatives, could avoid this steric constraint and should be considered as new, potentially effective compounds. The hydrophobic interaction between the side chain of inhibitor and the active site of the enzyme around position 108 was enhanced by the introduction of a longer and more hydrophobic side chain on TMP's 5-benzyl moiety. The prepared compounds, especially those bearing aromatic substituents, exhibited better binding affinities to both wild type and mutant enzymes than the parent compound. Binding affinities of these compounds correlated well with their antimalarial. activities against both wild type and resistant parasites. Molecular modeling of the binding of such compounds with pfDHFR also supported the experimental data and clearly showed that aromatic substituents play an important role in enhancing binding affinity. In addition, some compounds with 6-alkyl substituents showed relatively less decrease in binding constants with the mutant enzymes and relatively good antimalarial. activities against the parasites bearing the mutant enzymes.
• Designed multiple ligands for the treatment of type 2 diabetes mellitus and its complications: Discovery of (5-arylidene-4-oxo-2-thioxothiazolidin-3-yl)alkanoic acids active as novel dual-targeted PTP1B/AKR1B1 inhibitors
  作者：Rosanna Maccari、Gerhard Wolber、Massimo Genovese、Gemma Sardelli、Valerij Talagayev、Francesco Balestri、Simone Luti、Alice Santi、Roberta Moschini、Antonella Del Corso、Paolo Paoli、Rosaria Ottanà

  DOI：10.1016/j.ejmech.2023.115270

  日期：2023.4

  for the treatment of complex diseases with multifactorial pathogenesis, such as T2DM. Protein tyrosine phosphatase 1B (PTP1B) and aldose reductase (AKR1B1) are two enzymes crucially involved in the development of T2DM and its chronic complications and, therefore, dual inhibitors targeted to both these enzymes could provide novel agents for the treatment of this complex pathological condition. In continuing

  2 型糖尿病 (T2DM) 是一种严重的慢性疾病，其全球患病率正以惊人的速度增长。目前 T2DM 的治疗主要依靠药物组合来控制血糖水平，从而预防高血糖相关并发症的发生。多靶点药物的开发最近成为药物组合的有吸引力的替代品，用于治疗具有多因素发病机制的复杂疾病，例如 T2DM。蛋白酪氨酸磷酸酶 1B (PTP1B) 和醛糖还原酶 (AKR1B1) 是与 T2DM 及其慢性并发症的发展密切相关的两种酶，因此，针对这两种酶的双重抑制剂可以为治疗这种复杂的病理状况提供新的药物. 在继续寻找双靶点 PTP1B/AKR1B1 抑制剂的过程中，我们设计了新的 (5-arylidene-4-oxo-2-thioxothiazolidin-3-yl) 链烷酸。其中，3-(4-苯基丁氧基)亚苄基衍生物6f和7f具有针对两个靶标的有趣抑制活性，证明可以控制与 T2DM 和相关并发症的发展有关的特定细胞通路。