(S)-1-(3-iodophenyl)-3-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)urea | 1137837-74-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: (S)-1-(3-iodophenyl)-3-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)urea
• 英文别名: 1-(3-iodophenyl)-3-[(3S)-1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]urea
• CAS: 1137837-74-1
• 化学式: C₂₃H₁₉IN₄O₂
• 分子量: 510.334
• InChiKey: VLKJKVMACAESPP-OAQYLSRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  73.8
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-碘苯异氰酸酯 、 (S)-3-amino-1-methyl-5-phenyl-1H-benzo[e][1,4]diazepin-2(3H)-one 以 二氯甲烷 为溶剂， 反应 2.0h， 以94.5%的产率得到(S)-1-(3-iodophenyl)-3-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)urea
  参考文献：
  名称：

  Synthesis and in Vitro Characterization of Radioiodinatable Benzodiazepines Selective for Type 1 and Type 2 Cholecystokinin Receptors

  摘要：

  Radiolabeled antagonists of specific peptide receptors identify a higher number of receptor binding sites than agonists and may thus be preferable for in vivo tumor targeting. In this study, two novel radioiodinated 1,4-benzodiazepines, (S)-1-(3-iodophenyl)-3-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin3-yl)urea (9) and (R)-1-(3-iodophenyl)-3-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo(e][1,4]diazepin-3-yl)urea (7), were developed. They were characterized in vitro as high affinity selective antagonists at cholecystokinin types 1 and 2 (CCK1 and CCK2) receptors using receptor binding, calcium mobilization, and internalization studies. Their binding to human tumor tissues was assessed with in vitro receptor autoradiography and compared with an established peptidic CCK agonist radioligand. The I-125-labeled CCK1 receptor-selective compound 9 often revealed a substantially higher amount of CCK1 receptor binding sites in tumors than the agonist I-125-CCK. Conversely, the radioiodinated CCK2 receptor-selective compound 7 showed generally weaker tumor binding than I-125-CCK. In conclusion, compound 9 is an excellent radioiodinated nonpeptidic antagonist ligand for direct and selective labeling of CCK1 receptors in vitro. Moreover, it represents a suitable candidate to test antagonist binding to CCK1 receptor-expressing tumors in vivo.

  DOI：

  10.1021/jm801439x

文献信息

• Synthesis and in Vitro Characterization of Radioiodinatable Benzodiazepines Selective for Type 1 and Type 2 Cholecystokinin Receptors
  作者：Eyup Akgün、Meike Körner、Fan Gao、Kaleeckal G. Harikumar、Beatrice Waser、Jean Claude Reubi、Philip S. Portoghese、Laurence J. Miller

  DOI：10.1021/jm801439x

  日期：2009.4.9

  Radiolabeled antagonists of specific peptide receptors identify a higher number of receptor binding sites than agonists and may thus be preferable for in vivo tumor targeting. In this study, two novel radioiodinated 1,4-benzodiazepines, (S)-1-(3-iodophenyl)-3-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin3-yl)urea (9) and (R)-1-(3-iodophenyl)-3-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo(e][1,4]diazepin-3-yl)urea (7), were developed. They were characterized in vitro as high affinity selective antagonists at cholecystokinin types 1 and 2 (CCK1 and CCK2) receptors using receptor binding, calcium mobilization, and internalization studies. Their binding to human tumor tissues was assessed with in vitro receptor autoradiography and compared with an established peptidic CCK agonist radioligand. The I-125-labeled CCK1 receptor-selective compound 9 often revealed a substantially higher amount of CCK1 receptor binding sites in tumors than the agonist I-125-CCK. Conversely, the radioiodinated CCK2 receptor-selective compound 7 showed generally weaker tumor binding than I-125-CCK. In conclusion, compound 9 is an excellent radioiodinated nonpeptidic antagonist ligand for direct and selective labeling of CCK1 receptors in vitro. Moreover, it represents a suitable candidate to test antagonist binding to CCK1 receptor-expressing tumors in vivo.