(4S)-4-benzyl-2-(2,5-dihydroxyphenyl)-3,4-dihydro-5H-pyrido[1',2':1,2]imidazo-[4,5-d][1,3]diazepin-5-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑二氮卓类
• 英文名称: (4S)-4-benzyl-2-(2,5-dihydroxyphenyl)-3,4-dihydro-5H-pyrido[1',2':1,2]imidazo-[4,5-d][1,3]diazepin-5-one
• 英文别名: (13S)-13-benzyl-11-(2,5-dihydroxyphenyl)-2,8,10,12-tetrazatricyclo[7.5.0.02,7]tetradeca-1(9),3,5,7,11-pentaen-14-one
• 化学式: C₂₃H₁₈N₄O₃
• 分子量: 398.421
• InChiKey: BIJHBEFNVKYPRL-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  99.2
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  咪唑并[1,2-a]吡啶-2-胺 在 盐酸 、 碘 、 lead(IV) tetraacetate 、 三溴化硼 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 、 氯仿 、 水 为溶剂， 反应 14.0h， 生成 (4S)-4-benzyl-2-(2,5-dihydroxyphenyl)-3,4-dihydro-5H-pyrido[1',2':1,2]imidazo-[4,5-d][1,3]diazepin-5-one
  参考文献：
  名称：

  Pyrido-imidazodiazepinones as a new class of reversible inhibitors of human kallikrein 7

  摘要：

  The human tissue kallikrein-7 (KLK7) is a chymotryptic serine protease member of tissue kallikrein family. KLK7 is involved in skin homeostasis and inflammation. Excess of KLK7 activity is also associated with tumor metastasis processes, especially in ovarian carcinomas, prostatic and pancreatic cancers. Development of Kallikrein 7 inhibitors is thus of great interest in oncology but also for treating skin diseases. Most of the developed synthetic inhibitors present several drawbacks such as poor selectivity and unsuitable physico-chemical properties for in vivo use. Recently, we described a practical sequence for the synthesis of imidazopyridine-fused [1,3]-diazepines. Here, we report the identification of pyrido-imidazodiazepinone core as a new potential scaffold to develop selective and competitive inhibitors of kallikrein-related peptidase 7. Structure-activity relationships (SAR), inhibition mechanisms and selectivity as well as cytotoxicity against selected cancer cell lines were investigated. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.02.008