2-(5-methoxybiphenyl-3-yl)acetaldehyde | 1252013-90-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(5-methoxybiphenyl-3-yl)acetaldehyde
• 英文别名: 2-(3-Methoxy-5-phenylphenyl)acetaldehyde
• CAS: 1252013-90-3
• 化学式: C₁₅H₁₄O₂
• 分子量: 226.275
• InChiKey: MJWUTRCSXCQEHP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(5-methoxybiphenyl-3-yl)acetaldehyde 在 Jones reagent 作用下， 以 丙酮 为溶剂， 以2.63 g的产率得到5-甲氧基-3-联苯乙酸
  参考文献：
  名称：

  Structure-Based Approach to the Development of Potent and Selective Inhibitors of Dihydrofolate Reductase from Cryptosporidium

  摘要：

  Cryptosporidiosis is an emerging infectious disease that can be life-threatening in ail immune-compromised individual and causes gastrointestinal distress lasting up to 2 weeks in an immune-competent individual. There are few therapeutics available for effectively treating this disease. We have been exploring dihydrofolate reductase (DHFR) as a potential target in Cryptosporidium. On the basis of the structure of the DHFR enzyme from C. hominis, we have developed a novel scaffold that led to the discovery of potent (38 nM) and efficient inhibitors of this enzyme. Recently, we have advanced these inhibitors to the next stage of development. Using the Structures of both the protozoal and human enzymes. we have developed inhibitors with nanomolar potency (1.1 nM) against the pathogenic enzyme and high levels (1273-fold) of selectivity over the human enzyme.

  DOI：

  10.1021/jm8009124
• 作为产物：
  描述：

  在 盐酸 、 水 作用下， 反应 1.0h， 以0.3343 g的产率得到2-(5-methoxybiphenyl-3-yl)acetaldehyde
  参考文献：
  名称：

  炭疽芽孢杆菌二氢叶酸还原酶缩合复杂结构-活性关系的靶向突变

  摘要：

  几种抗叶酸剂，包括甲氧苄氨嘧啶 (TMP) 和一系列炔丙基连接的类似物，可结合来自炭疽芽孢杆菌的二氢叶酸还原酶(BaDHFR) 的亲和力低于其他细菌物种的典型亲和力。为了指导 BaDHFR 的先导优化，我们探索了一种确定结构-活性关系的新方法，由此酶被改变而类似物保持不变，从根本上扭转了标准的实验设计。酶的活性位点突变体 Ba(F96I)DHFR 和 Ba(Y102F)DHFR 被创建并用酶抑制测定和晶体结构进行评估。对于 Y102F 突变体，抗叶酸剂的亲和力增加了 60 倍，这表明与 Tyr 102 的相互作用对亲和力至关重要。与 TMP 和炔丙基连接的抑制剂结合的酶的晶体结构揭示了 TMP 抗性的基础，并阐明了 Tyr 102 对嘧啶和芳环之间的亲脂性接头的影响。

  DOI：

  10.1021/jm100727t

文献信息

• Structure-Based Approach to the Development of Potent and Selective Inhibitors of Dihydrofolate Reductase from <i>Cryptosporidium</i>
  作者：David B. Bolstad、Erin S. D. Bolstad、Kathleen M. Frey、Dennis L. Wright、Amy C. Anderson

  DOI：10.1021/jm8009124

  日期：2008.11.13

  Cryptosporidiosis is an emerging infectious disease that can be life-threatening in ail immune-compromised individual and causes gastrointestinal distress lasting up to 2 weeks in an immune-competent individual. There are few therapeutics available for effectively treating this disease. We have been exploring dihydrofolate reductase (DHFR) as a potential target in Cryptosporidium. On the basis of the structure of the DHFR enzyme from C. hominis, we have developed a novel scaffold that led to the discovery of potent (38 nM) and efficient inhibitors of this enzyme. Recently, we have advanced these inhibitors to the next stage of development. Using the Structures of both the protozoal and human enzymes. we have developed inhibitors with nanomolar potency (1.1 nM) against the pathogenic enzyme and high levels (1273-fold) of selectivity over the human enzyme.
• Targeted Mutations of <i>Bacillus anthracis</i> Dihydrofolate Reductase Condense Complex Structure−Activity Relationships
  作者：Jennifer M. Beierlein、Nanda G. Karri、Amy C. Anderson

  DOI：10.1021/jm100727t

  日期：2010.10.28

  and crystal structures. The affinities of the antifolates increase up to 60-fold with the Y102F mutant, suggesting that interactions with Tyr 102 are critical for affinity. Crystal structures of the enzymes bound to TMP and propargyl-linked inhibitors reveal the basis of TMP resistance and illuminate the influence of Tyr 102 on the lipophilic linker between the pyrimidine and aryl rings. Two new inhibitors

  几种抗叶酸剂，包括甲氧苄氨嘧啶 (TMP) 和一系列炔丙基连接的类似物，可结合来自炭疽芽孢杆菌的二氢叶酸还原酶(BaDHFR) 的亲和力低于其他细菌物种的典型亲和力。为了指导 BaDHFR 的先导优化，我们探索了一种确定结构-活性关系的新方法，由此酶被改变而类似物保持不变，从根本上扭转了标准的实验设计。酶的活性位点突变体 Ba(F96I)DHFR 和 Ba(Y102F)DHFR 被创建并用酶抑制测定和晶体结构进行评估。对于 Y102F 突变体，抗叶酸剂的亲和力增加了 60 倍，这表明与 Tyr 102 的相互作用对亲和力至关重要。与 TMP 和炔丙基连接的抑制剂结合的酶的晶体结构揭示了 TMP 抗性的基础，并阐明了 Tyr 102 对嘧啶和芳环之间的亲脂性接头的影响。