5-cycloheptylmethyl-2-naphthalen-2-yl-1H-imidazole-4-carboxylic acid (3,5-(dimethoxycarbonyloxymethyl)phenyl)amide | 269070-89-5

• 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: 5-cycloheptylmethyl-2-naphthalen-2-yl-1H-imidazole-4-carboxylic acid (3,5-(dimethoxycarbonyloxymethyl)phenyl)amide
• 英文别名: 5-Cycloheptylmethyl-2-naphthalen-2-yl-1H-imidazole-4-carboxylic Acid (3,5-bis-methoxycarbonyloxymethyl-phenyl)-amide；[3-[[5-(cycloheptylmethyl)-2-naphthalen-2-yl-1H-imidazole-4-carbonyl]amino]-5-(methoxycarbonyloxymethyl)phenyl]methyl methyl carbonate
• CAS: 269070-89-5
• 化学式: C₃₄H₃₇N₃O₇
• 分子量: 599.684
• InChiKey: GENZYQMKEBLMMM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  44
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  129
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5-cycloheptylmethyl-2-naphthalen-2-yl-1H-imidazole-4-carboxylic acid (3,5-(dimethoxycarbonyloxymethyl)phenyl)amide 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 以83%的产率得到5-cycloheptylmethyl-2-(naphthalen-2-yl)-1H-imidazole-4-carboxylic acid (3,5-bis-hydroxymethylphenyl)amide
  参考文献：
  名称：

  Gastrin and cholecystokinin receptor ligands

  摘要：

  化合物的结构式（I）及其药学上可接受的盐是胃泌素和/或胆囊收缩素受体的配体。X和Y独立地为═N—，—N(R5)—═CH—，—S—或—O—。n为1至4；R1为H或C1至C15烃基；R2从H，Me，Et，Pr和OH中选择；R3从H，Me，Et和Pr中选择；或（当n大于1时）每个R3独立地从H，Me，Et和Pr中选择，或相邻碳原子上的两个R3基团连接形成C3至C6碳环，或R2和R3在同一碳原子上共同表示一个═O基团；R4为C1至C15烃基；Z为—(NR7)a—CO—(NR8)b—（其中a为0或1，b为0或1，—CO—NR7—CH2—CO—NR8—，—CO—O—，—CH2—CH2—，—CH═CH—，—CH2—NR8—或键；Q为—R9V，或（II），（其中R9为—CH2—；—CH2—CH2—；或（III），R9和R8，与R8连接的氮原子一起形成被V取代的哌啶或吡咯烷环；V为—CO—NH—SO2—Ph，—SO2—NH—CO—Ph，—CH2OH，或具有式—R10U的基团，（其中U为—COOH，四唑基，—CONHOH—或—SO3H；R10为键；C1至C6烃基亚烷，—O—（C1至C3亚烷基）—；—SO2NR11—CHR12—；—CO—NR11—CHR12—，或—NH—（CO）c—CH2—，其中c为0或1）。

  公开号：

  US06479531B1
• 作为产物：
  描述：

  环庚醋酸 在 4-二甲氨基吡啶 、 Oxone 、 sodium hydroxide 、 ammonium acetate 、 1-羟基苯并三唑 、 溶剂黄146 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 83.0h， 生成 5-cycloheptylmethyl-2-naphthalen-2-yl-1H-imidazole-4-carboxylic acid (3,5-(dimethoxycarbonyloxymethyl)phenyl)amide
  参考文献：
  名称：

  Scaffold Hopping with Molecular Field Points:  Identification of a Cholecystokinin-2 (CCK₂) Receptor Pharmacophore and Its Use in the Design of a Prototypical Series of Pyrrole- and Imidazole-Based CCK₂ Antagonists

  摘要：

  A new molecular modeling approach has been used to derive a pharmacophore of the potent and selective cholecystokinin-2 (CCK2) receptor antagonist 5 (JB93182), based on features shared with two related series. The technique uses "field points" as simple and effective descriptions of the electrostatic and van der Waals maxima and minima surrounding a molecule equipped with XED (extended electron distribution) charges. Problems associated with the high levels of biliary elimination of 5 in vivo required us to design a compound with significantly lower molecular weight without sacrificing its nanomolar levels of in vitro activity. Two new series of compounds were designed to mimic the arrangement of field points present in the pharmacophore rather than its structural elements. In a formal sense, two of the three amides in 5 were replaced with either a simple pyrrole or imidazole, while some features thought to be essential for the high levels of in vitro activity of the parent compounds were retained and others deleted. These compounds maintained activity and selectivity for this receptor over CCK1. In addition, the reduction in molecular weight coupled with lower polarities greatly reduced levels of biliary elimination associated with 5. This makes them good lead compounds for development of drug candidates whose structures are not obviously related to those of the parents and represents the first example of scaffold hopping using molecular field points.

  DOI：

  10.1021/jm049069y