2-[2,4-dioxo-5-phenyl-3-(phenylhydrazono)-2,3,4,5-tetrahydro benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-phenylacetamide | 161455-91-0

• 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-[2,4-dioxo-5-phenyl-3-(phenylhydrazono)-2,3,4,5-tetrahydro benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-phenylacetamide
• 英文别名: 2-[2,4-dioxo-5-phenyl-3-(phenylhydrazinylidene)-1,5-benzodiazepin-1-yl]-N-phenyl-N-propan-2-ylacetamide
• CAS: 161455-91-0
• 化学式: C₃₂H₂₉N₅O₃
• 分子量: 531.614
• InChiKey: ZKKTYLLVXDUAFG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  40
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  85.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[2,4-dioxo-5-phenyl-3-(phenylhydrazono)-2,3,4,5-tetrahydro benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-phenylacetamide 在 溶剂黄146 、 三乙胺 、 锌 作用下， 反应 17.5h， 生成 tert-butyl 2-[3-[[2,4-dioxo-1-[2-oxo-2-(N-propan-2-ylanilino)ethyl]-5-phenyl-1,5-benzodiazepin-3-yl]carbamoylamino]phenoxy]acetate
  参考文献：
  名称：

  Discovery of 1,5-Benzodiazepines with Peripheral Cholecystokinin (CCK-A) Receptor Agonist Activity (II):  Optimization of the C3 Amino Substituent

  摘要：

  Analogs of the previously reported 1,5-benzodiazepine peripheral cholecystokinin (CCK-A) receptor agonist 1 were prepared which explore substitution and/or replacement of the C-3 phenyl urea moiety. Agonist efficacy on the isolated guinea pig gallbladder (GPGB) was retained with a variety of substituted ureas and amide analogs. Three compounds were identified which were orally active in the mouse gallbladder emptying assay (MGBE). The 2-indolamide (52) and N-(carboxymethyl)-2-indolamide (54) derivatives had improved affinity for the human CCK-A receptor but reduced agonist efficacy on the GPGB. Neither indolamide was orally active in a rat feeding assay. In contrast, the (3-carboxyphenyl)urea derivative (29, GW7854) had moderately increased affinity for the human CCK-B receptor but was a potent full agonist on the GPGB and was orally active in both the MGBE and rat feeding assays. GW7854 was a full agonist (EC(50) = 60 nM) for calcium mobilization on CHO K1 cells expressing hCCK-A receptors and a potent antagonist; of CCK-8 (pA(2) = 9.1) on CHO K1 cells expressing hCCK-B receptors. GW7854 is a potent mixed CCK-A agonist/CCK-B antagonist which is orally active in two in vivo models of CCK-A-mediated agonist activity.

  DOI：

  10.1021/jm9601664
• 作为产物：
  描述：

  2-bromo-N-isopropyl-N-phenyl-acetamide 在 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 2-[2,4-dioxo-5-phenyl-3-(phenylhydrazono)-2,3,4,5-tetrahydro benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-phenylacetamide
  参考文献：
  名称：

  Discovery of 1,5-Benzodiazepines with Peripheral Cholecystokinin (CCK-A) Receptor Agonist Activity (II):  Optimization of the C3 Amino Substituent

  摘要：

  Analogs of the previously reported 1,5-benzodiazepine peripheral cholecystokinin (CCK-A) receptor agonist 1 were prepared which explore substitution and/or replacement of the C-3 phenyl urea moiety. Agonist efficacy on the isolated guinea pig gallbladder (GPGB) was retained with a variety of substituted ureas and amide analogs. Three compounds were identified which were orally active in the mouse gallbladder emptying assay (MGBE). The 2-indolamide (52) and N-(carboxymethyl)-2-indolamide (54) derivatives had improved affinity for the human CCK-A receptor but reduced agonist efficacy on the GPGB. Neither indolamide was orally active in a rat feeding assay. In contrast, the (3-carboxyphenyl)urea derivative (29, GW7854) had moderately increased affinity for the human CCK-B receptor but was a potent full agonist on the GPGB and was orally active in both the MGBE and rat feeding assays. GW7854 was a full agonist (EC(50) = 60 nM) for calcium mobilization on CHO K1 cells expressing hCCK-A receptors and a potent antagonist; of CCK-8 (pA(2) = 9.1) on CHO K1 cells expressing hCCK-B receptors. GW7854 is a potent mixed CCK-A agonist/CCK-B antagonist which is orally active in two in vivo models of CCK-A-mediated agonist activity.

  DOI：

  10.1021/jm9601664

文献信息

• 1,5-benzodiazepine derivatives having CCK antagonistic or agonistic
  申请人：Glaxo Wellcome Inc.

  公开号：US05646140A1

  公开（公告）日：1997-07-08

  This invention pertains to novel benzodiazepine compounds of formula (I) ##STR1## which exhibit agonistic activity for CCK-A receptors, enabling them to modulate the hormones gastrin and cholecystokinin (CCK) in mammals for use in medicine as anorectic agents in the regulation of appetite, the treatment of obesity and the maintenance of weight loss.

  本发明涉及公式（I）的新型苯二氮平类化合物 ##STR1## 它们表现出CCK-A受体的激动作用，使它们能够在哺乳动物中调节荷尔蒙胃泌素和胆囊收缩素（CCK），用于医学上作为抑制食欲代理、治疗肥胖症和维持体重减轻。
• Use of 1,5-benzo\x9bb!1,4-diazepines to control gastric emptying
  申请人：Glaxo Wellcome Inc.

  公开号：US05910495A1

  公开（公告）日：1999-06-08

  A method of controlling gastric emptying in patients having an early non-insulin-dependent diabetic condition and exhibiting rapid gastric emptying comprising the administration of an effective gastric emptying controlling amount of a compound of Formula (I) ##STR1## or a physiologically acceptable salt or solvate thereof.

  一种控制早期非胰岛素依赖性糖尿病患者胃排空的方法，其中这些患者表现出快速的胃排空，该方法包括给予化合物I式（见下文）或其生理上可接受的盐或溶剂的有效胃排空控制剂量的管理。 ##STR1##