3-amino-2,3-dihydro-1-(2-oxo-2-phenylethyl)-5-phenyl-1H-1,4-benzodiazepin-2-one | 174276-56-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-amino-2,3-dihydro-1-(2-oxo-2-phenylethyl)-5-phenyl-1H-1,4-benzodiazepin-2-one
• 英文别名: 3-amino-1,3-dihydro-1-phenacyl-5-phenyl-2H-1,4-benzodiazepin-2-one；3-amino-1-phenacyl-5-phenyl-3H-1,4-benzodiazepin-2-one
• CAS: 174276-56-3
• 化学式: C₂₃H₁₉N₃O₂
• 分子量: 369.423
• InChiKey: LLABBYXQQFABRQ-UHFFFAOYSA-N

物化性质

• 沸点：
  619.3±55.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  75.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-叔丁氧羰基-L-丙氨酸 、 3-amino-2,3-dihydro-1-(2-oxo-2-phenylethyl)-5-phenyl-1H-1,4-benzodiazepin-2-one 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 以93%的产率得到3-(N'-(tert-Butoxycarbonyl)-L-alaninyl)amino-2,3-dihydro-1-(2-oxo-2-phenylethyl)-5-phenyl-1H-1,4-benzodiazepin-2-one
  参考文献：
  名称：

  CYCLOALKYL, LACTAM, LACTONE AND RELATED COMPOUNDS, PHARMACEUTICAL COMPOSITIONS COMPRISING SAME, AND METHODS FOR INHIBITING BETA-AMYLOID PEPTIDE RELEASE AND/OR ITS SYNTHESIS BY USE OF SUCH COMPOUNDS

  摘要：

  公开号：

  EP0951466B1
• 作为产物：
  描述：

  1,3-二氢-5-苯基-1,4-苯并二氮杂卓-2-酮 在 Ru-carbon sodium hydroxide 、 potassium tert-butylate 、 氢气 、 甲基三辛基氯化铵 、 亚硝酸异戊酯 作用下， 以 甲醇 、 甲苯 为溶剂， -20.0~60.0 ℃ 、810.6 kPa 条件下， 反应 8.75h， 生成 3-amino-2,3-dihydro-1-(2-oxo-2-phenylethyl)-5-phenyl-1H-1,4-benzodiazepin-2-one
  参考文献：
  名称：

  New 1,4-Benzodiazepin-2-one Derivatives as Gastrin/Cholecystokinin-B Antagonists.

  摘要：

  研究人员制备了一系列新型 1-芳酰基甲基-1，3-二氢-2H-1，4-苯并二氮杂卓-2-酮衍生物，并对其作为胃泌素/胆囊收缩素（CCK）-B 受体拮抗剂的活性进行了评估。体外结合研究表明，一些衍生物对胃泌素/CCK-B 受体具有很强的亲和力，对外周 CCK（CCK-A）受体具有很高的选择性。此外，在大鼠体内模型中，这些化合物静脉注射后能有效抑制五肽胃泌素诱导的胃酸分泌。该系列化合物的结构-活性关系研究表明，1-[(R)-2, 3-二氢-1-（2-甲基苯乙酰基）-2-氧代-5-苯基-1H-1, 4-苯并二氮杂卓-3-基]-3-（3-甲基苯基）脲（35b，YM022）是最佳化合物，其 IC50 值分别为 0.对胃泌素、CCK-B 和 CCK-A 受体的 IC50 值分别为 0.17、0.11 和 150nM，对大鼠的 ED50 值为 9.5nmol/kg（静脉注射）。YM022 的前体是一种 (R)-3-氨基-1, 3-二氢-2H-1, 4-苯并二氮杂卓-2-酮衍生物（(R)-25），其绝对构型是通过对其 (S)-mandelate 的 X 射线晶体学分析确定的。YM022 是一种强效的选择性胃泌素/CCK-B 受体拮抗剂，可抑制胃酸分泌，但不会引起胃泌素介导的副作用，如高胃泌素血症和胃黏膜增生。

  DOI：

  10.1248/cpb.43.2159

文献信息

• Cycloalkyl, lactam, lactone and related compounds, pharmaceutical compositions comprising same, and methods for inhibiting beta-amyloid peptide release and/or its synthesis by use of such compounds
  申请人：——

  公开号：US20020045747A1

  公开（公告）日：2002-04-18

  Disclosed are compounds which inhibit &bgr;-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits &bgr;-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.

  公开了抑制β-淀粉样肽释放和/或其合成的化合物，因此可用于治疗阿尔茨海默病。还公开了包含抑制β-淀粉样肽释放和/或其合成的化合物的药物组合物，以及使用这些药物组合物预防性和治疗性治疗阿尔茨海默病的方法。
• Cyclic amino acid compounds pharmaceutical compositions comprising same and methods for inhibiting &bgr;-amyloid peptide release and/or its synthesis by use of such compounds
  申请人：Elan Pharmaceuticals, Inc.

  公开号：US06528505B1

  公开（公告）日：2003-03-04

  Disclosed are compounds which inhibit &bgr;-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits &bgr;-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.

  公开了抑制β-淀粉样肽释放和/或其合成的化合物，因此可用于治疗阿尔茨海默病。还公开了包含抑制β-淀粉样肽释放和/或其合成的化合物的药物组合物，以及使用这些药物组合物预防性和治疗性治疗阿尔茨海默病的方法。
• Deoxyamino acid compounds, pharmaceutical compositions comprising same, and methods for inhibiting &bgr;-amyloid peptide release and/or its synthesis by use of such compounds
  申请人：Elan Pharmaceuticals, Inc.

  公开号：US06509331B1

  公开（公告）日：2003-01-21

  Disclosed are compounds which inhibit &bgr;-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits &bgr;-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.

  公开了抑制β-淀粉样肽释放和/或其合成的化合物，因此可用于治疗阿尔茨海默病。还公开了包含抑制β-淀粉样肽释放和/或其合成的化合物的药物组合物，以及使用这些药物组合物预防性和治疗性地治疗阿尔茨海默病的方法。
• Benzodiazepine aryl urea derivatives
  申请人：Yamanouchi Pharmaceutical Co., Ltd.

  公开号：US05541182A1

  公开（公告）日：1996-07-30

  This invention relates to novel benzodiazepine derivatives represented by the following general formula (I) or pharmaceutically acceptable salts thereof, ##STR1## (wherein R.sup.1 is an aryl group, or an aromatic heterocyclic radical of 5-membered monocyclic, 6-membered monocyclic or 5- and 6-membered bicyclic structure, which may optionally be substituted; and R.sup.2 is an aryl group which may optionally be substituted), to medicinal compositions comprising the same, and to a process for producing the same. The compounds of formula (I) shown above exhibit antagonism for the CCK-B receptor and the action of depressing the gastric acid secretion caused by the stimulus of pentagastrin, and are therefore useful as a drug for the relief of diseases related to the CCK-B receptor and the gastrin receptor.

  本发明涉及以下通式(I)或其药学上可接受的盐所表示的新型苯二氮平衍生物，其中R1是芳基基团或5元单环、6元单环或5-和6元双环结构的芳香杂环基团，可以选择性地被取代；R2是可以选择性地被取代的芳基基团。本发明还涉及包含这些化合物的药物组合物，以及制备它们的方法。上述化合物的通式(I)表现出对CCK-B受体的拮抗作用，以及对因五胃素刺激引起的胃酸分泌的抑制作用，因此可用作缓解与CCK-B受体和胃泌素受体相关的疾病的药物。
• Cycloalkyl, lactam, lactone and related compounds, pharmaceutical compositions comprising same, and methods for inhibiting B-amyloid peptide release and/or its synthesis by use of such compounds
  申请人：——

  公开号：US20020173504A1

  公开（公告）日：2002-11-21

  Disclosed are compounds which inhibit &bgr;-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits &bgr;-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.

  本发明涉及抑制&bgr;-淀粉样肽的释放和/或合成的化合物，因此具有治疗阿尔茨海默病的效用。还公开了包含抑制&bgr;-淀粉样肽释放和/或合成的化合物的药物组合物，以及使用这种药物组合物预防和治疗阿尔茨海默病的方法。