2-(2,4-dioxo-5-phenyl-3-{3-[3-(1H-tetrazol-5-yl)-phenyl]-ureido}2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl) N-isopropyl-N-phenylacetamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(2,4-dioxo-5-phenyl-3-{3-[3-(1H-tetrazol-5-yl)-phenyl]-ureido}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-{3-[3-(1H-tetrazol-5-yl)-phenyl]-ureido}2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-phenylacetamide；2-[2,4-dioxo-5-phenyl-3-[[3-(2H-tetrazol-5-yl)phenyl]carbamoylamino]-1,5-benzodiazepin-1-yl]-N-phenyl-N-propan-2-ylacetamide
• 化学式: C₃₄H₃₁N₉O₄
• 分子量: 629.678
• InChiKey: IUSBBWZHXHVOMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  47
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  157
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 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 6.5h， 生成 2-(2,4-dioxo-5-phenyl-3-{3-[3-(1H-tetrazol-5-yl)-phenyl]-ureido}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

• 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。
• [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。
• 1,5-BENZODIAZEPINE DERIVATIVES HAVING CCK ANTAGONISTIC AND OR AGONISTIC ACTIVITY
  申请人：GLAXO WELLCOME INC.

  公开号：EP0694039B1

  公开（公告）日：2001-01-24
• US5646140A
  申请人：——

  公开号：US5646140A

  公开（公告）日：1997-07-08