2-(3-amino-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydrobenzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-phenylacetamide | 184944-86-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-(3-amino-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydrobenzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-phenylacetamide
• 英文别名: GI155056；TCMDC-143071；2-(3-Amino-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo [b] ›1, 4! diazepine-1-yl)-N-isopropyl-N-phenyl acetamide；2-(3-amino-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-phenyl-acetamide；2-(3-amino-2,4-dioxo-5-phenyl-1,5-benzodiazepin-1-yl)-N-phenyl-N-propan-2-ylacetamide
• CAS: 184944-86-3
• 化学式: C₂₆H₂₆N₄O₃
• 分子量: 442.517
• InChiKey: SNGMAIJHCWVIEO-UHFFFAOYSA-N

物化性质

• 沸点：
  732.3±60.0 °C(Predicted)
• 密度：
  1.259±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  87
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(3-amino-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydrobenzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-phenylacetamide 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 25.0 ℃ 、344.73 kPa 条件下， 反应 88.83h， 生成 2-[3-[(3-aminophenyl)carbamoylamino]-2,4-dioxo-5-phenyl-1,5-benzodiazepin-1-yl]-N-phenyl-N-propan-2-ylacetamide
  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 、 溶剂黄146 、 锌 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 39.0h， 生成 2-(3-amino-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydrobenzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-phenylacetamide
  参考文献：
  名称：

  3-[2-(N-Phenylacetamide)]-1,5-benzodiazepines:  Orally Active, Binding Selective CCK-A Agonists

  摘要：

  A series of modifications were made to the C-3 substituent of the 1,5-benzodiazepine CCK-A agonist 1. Replacement of the inner urea NH and addition of a methyl group to generate a C-3 quaternary carbon resulted in acetamide 6, which showed CCK-A receptor binding selectivity and sub-micromolar agonist activity in vitro. Benzodiazepine 6 was active in an in. vivo mouse gallbladder emptying assay and represents a novel orally active, binding selective CCK-A agonist.

  DOI：

  10.1021/jm960205b

文献信息

• 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.

  一种控制患有早期非胰岛素依赖型糖尿病病情且胃排空迅速的患者胃排空的方法，包括给予化合物的有效胃排空控制量，该化合物为下式（I）的化合物或其生理上可接受的盐或溶剂。
• Radiosynthesis of carbon-11-labelled GI181771, a new selective CCK-A agonist
  作者：F. Dollé、L. Martarello、Y. Bramoullé、M. Bottlaender、A.D. Gee

  DOI：10.1002/jlcr.947

  日期：2005.6

  o)benzoic acid, GI181771 ((S)-1) has been isotopically labelled with carbon-11 at its urea site using [11C]phosgene in a one-pot two-step process, via the intermediate preparation of an [11C]isocyanate derivative. Optimized conditions for the preparation of (S)-[11C]-1 were the following: (1) Trapping of [11C]phosgene (radiosynthesized from cyclotron-produced [11C]methane via [11C]carbon tetrachloride

  新型 CCK-A 激动剂，(S)-3-(3-1-[(isopropylphenylcarbamoyl)methyl]-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[ b][1,4]diazepin-3-yl}ureido)benzoic acid, GI181771 ((S)-1) 已在其尿素位点使用 [11C] 光气在一锅二合一中用碳 11 同位素标记一步法，通过中间体制备[11C]异氰酸酯衍生物。制备 (S)-[11C]-1 的优化条件如下： (1) 捕集 [11C] 光气（从回旋加速器产生的 [11C] 甲烷通过 [11C] 四氯化碳放射合成，对已发表的工艺稍作修改) 在室温下在 300 µl 含有 0. 6 µmol 合适的（结构复杂的）手性胺得到相应的 [11C] 异氰酸酯，然后 (2) 添加过量的 3-氨基苯甲酸（40 µmol
• [EN] 1,5-BENZODIAZEPINE DERIVATIVES HAVING CCK ANTAGONISTIC OR AGONISTIC ACTIVITY<br/>[FR] DERIVES DE 1,5-BENZODIAZEPINE PRESENTANT UNE ACTIVITE D'ANTAGONISTES OU D'AGONISTES POUR LA CCK
  申请人：GLAXO INC.

  公开号：WO1994024149A1

  公开（公告）日：1994-10-27

  (EN) Novel benzodiazepine compounds of formula (1) 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.(FR) Nouveaux composés de benzodiazépine de formule (1) présentant une activité d'agonistes pour les récepteurs de la CCK-A leur permettant de moduler les hormones gastrine et cholécystoquinine (CCK) chez les mammifères. Lesdits composés sont destinés à être utilisés comme agents anorexiques dans la régulation de l'appétit, le traitement de l'obésité et la stabilisation de la perte de poids.

  （中文）公式（1）的新型苯二氮平类化合物表现出对CCK-A受体的激动作用，使它们能够在哺乳动物中调节胃泌素和胆囊收缩素（CCK）的激素，用于医学上的压食剂，以调节食欲，治疗肥胖和维持体重减轻。
• 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。
• Structurally similar small molecule photoaffinity CCK-A agonists and antagonists as novel tools for directly probing 7TM receptor-ligand interactions
  作者：James W. Darrow、Elizabeth M. Hadac、Laurence J. Miller、Elizabeth E. Sugg

  DOI：10.1016/s0960-894x(98)00548-4

  日期：1998.11

  Incorporation of photolabile benzoyl (2a-d) or trifluoromethyl-3H-diazirine (3a-d) substituents into 1,5-benzodiazepine ligands did not significantly impair the rat CCK-A binding affinity of either agonists or antagonists. The modified agonist ligands also retained functional potency and efficacy in the rat amylase assay. Despite their strong structural similarity, the SAR of this limited set of compounds suggests that these small molecule antagonists and agonists might differ in their mode of binding to the CCK-A receptor. Preliminary affinity results show that representative agonists and antagonists from these series can be used to efficiently covalently label the CCK-A receptor. (C) 1998 Elsevier Science Ltd. All rights reserved.