1,3-dihydro-1-(2-hydroxyethyl)-3-(R,S)-amino-5-phenyl-1H-1,4-benzodiazepin-2-one | 136051-17-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 1,3-dihydro-1-(2-hydroxyethyl)-3-(R,S)-amino-5-phenyl-1H-1,4-benzodiazepin-2-one
• 英文别名: 3-(RS)-Amino-1,3-dihydro-1-(2-hydroxyethyl)-5-phenyl-2H-1,4-benzodiazepin-2-one；3-amino-1-(2-hydroxyethyl)-5-phenyl-3H-1,4-benzodiazepin-2-one
• CAS: 136051-17-7
• 化学式: C₁₇H₁₇N₃O₂
• 分子量: 295.341
• InChiKey: OVVHEXPPNCSLQB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,3-dihydro-1-(2-hydroxyethyl)-3-(R,S)-amino-5-phenyl-1H-1,4-benzodiazepin-2-one 在 氢氧化钾 、 三乙胺 、 三丁基氧化锡 作用下， 以 甲醇 、 水 为溶剂， 生成 4-{2-[2-Oxo-5-phenyl-3-(3-m-tolyl-ureido)-2,3-dihydro-benzo[e][1,4]diazepin-1-yl]-ethoxycarbonylamino}-butyric acid
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of highly potent dual histamine H2 and gastrin receptor antagonists

  摘要：

  The chemical modification of the dual histamine H-2 and gastrin receptor antagonists described in our preceding paper, particularly the modification of spacers as well as the alteration of their connecting bonds at the gastrin receptor antagonist site (GA) from the amide bond to the carbamate bond, significantly improved not only their dual activity but also the GA versus CCK-A receptor selectivity. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/s0960-894x(96)00249-1
• 作为产物：
  描述：

  benzyl N-[1-(2-hydroxyethyl)-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]carbamate 在 氢溴酸 作用下， 以 四氢呋喃 为溶剂， 以366 mg的产率得到1,3-dihydro-1-(2-hydroxyethyl)-3-(R,S)-amino-5-phenyl-1H-1,4-benzodiazepin-2-one
  参考文献：
  名称：

  开发1,4-苯并二氮杂类胆囊收缩素B型拮抗剂。

  摘要：

  描述了一系列3-（芳基脲基）-5-苯基-1,4-苯并二氮杂卓，肽激素胆囊收缩素（CCK）的非肽拮抗剂。通过对CCK-A选择性3-甲酰胺基-1,4-苯并二氮杂卓MK-329的合理修饰而衍生，本文记载了有效的，口服有效的化合物的开发，其中对CCK-B受体亚型具有选择性。从这些研究中得出的主要铅结构是L-365,260，该化合物已提交临床评估。讨论了通过适当的结构修饰来调节这些苯并二氮杂the的受体相互作用的能力的细节，这暗示了进一步完善这类化合物的CCK-B受体亲和力和选择性的可能性。

  DOI：

  10.1021/jm00078a018

文献信息

• New benzodiazepine analogs
  申请人：MERCK & CO. INC.

  公开号：EP0523845A2

  公开（公告）日：1993-01-20

  Pharmaceutical compositions containing benzodiazepine analogs of the formula : are disclosed which are antagonists of gastrin and cholecystokinin (CCK) with enhanced aqueous solubility and have properties useful in the treatment of oncologic disorders, controlling pupil constriction in the eye, or treating a withdrawal response produced by treatment or abuse of drugs or alcohol.

  包含苯二氮䓬类似物的制药组合物的公开，这些类似物是胃泌素和胆囊收缩素（CCK）的拮抗剂，具有增强的水溶性，并具有在治疗肿瘤性疾病、控制眼睛瞳孔收缩或治疗由药物或酒精滥用引起的戒断反应中有用的特性。
• Benzodiazepine analogs for treating panic syndrome and for directly inducing analgesia
  申请人：MERCK & CO. INC.

  公开号：EP0434364A3

  公开（公告）日：1992-04-01

  Benzodiazepine analogs of the formula: are disclosed which are antagonists of gastrin and cholecystokinin (CCK) and have properties useful for treating panic syndrome and for directly inducing analgesia.

  公开了以下化学式的苯二氮䓬类似物：这些类似物是胃泌素和胆囊收缩素（CCK）的拮抗剂，并具有用于治疗惊恐综合症和直接诱导镇痛的特性。
• New benziodiazepine analogs
  申请人：MERCK & CO. INC.

  公开号：EP0434360A1

  公开（公告）日：1991-06-26

  Benzodiazepine analogs of the formula: are disdosed which are antagonists of gastrin and cholecystokinin (CCK) with enhanced aqueous solubility and have properties useful in the treatment of disorders of gastric secretion, appetite regulation, gastrointestinal motility, pancreatic secretion, and dopaminergic function, as well as in treatment producing potentiation of morphine and other opiate analgesics.

  已开发出一种苯二氮䓬类似物，其为胃泌素和胆囊收缩素（CCK）的拮抗剂，具有增强的水溶性，并具有在治疗胃分泌障碍、食欲调节、胃肠蠕动、胰腺分泌和多巴胺功能障碍方面有用的特性，同时在产生吗啡和其他阿片类镇痛药的增效治疗中也具有作用。
• Benzodiazepine analogs
  申请人：Merck & Co., Inc.

  公开号：US05324726A1

  公开（公告）日：1994-06-28

  Benzodiazepine analogs of the formula: ##STR1## wherein: R.sup.3 is ##STR2## --NH(CH.sub.2).sub.2 --.sub.3 NHCOR.sup.7, ##STR3## or --X.sup.11 NR.sup.18 SO.sub.2 (CH.sub.2).sub.q R.sup.7 ; R.sup.7 is O,S,HH, or NR.sup.15 with the proviso that X.sup.7 can be NR.sup.15 only when R.sup.1 is not H. are disclosed which are antagonists of gastrin and cholecystokinin (CCK) with enhanced aqueous solubility and have properties useful in the treatment of disorders of gastric secretion, appetite regulation, gastrointestinal motility, pancreatic secretion, and dopaminergic function, as well as in treatment producing potentiation of morphine and other opiate analgesics.

  公开了一种Benzodiazepine的类似物，其化学式为：##STR1## 其中：R.sup.3是##STR2## --NH(CH.sub.2).sub.2 --.sub.3 NHCOR.sup.7, ##STR3## 或--X.sup.11 NR.sup.18 SO.sub.2 (CH.sub.2).sub.q R.sup.7；R.sup.7是O、S、HH或NR.sup.15，但X.sup.7只有在R.sup.1不是H时才能是NR.sup.15。这些类似物是胃泌素和胆囊收缩素（CCK）的拮抗剂，具有增强的水溶性和有用于治疗胃分泌、食欲调节、胃肠动力、胰腺分泌和多巴胺功能障碍的特性，以及用于产生吗啡和其他鸦片类镇痛药的增强作用的治疗。
• Design, synthesis, and pharmacological evaluation of dual histamine H2 and gastrin receptor antagonists
  作者：Yasuyuki Kawanishi、Shoichi Ishihara、Tadahiko Tsushima、Kaoru Seno、Masanori Miyagoshi、Sanji Hagishita、Michio Ishikawa、Noriko Shima、Mayumi Shimamura、Yasunobu Ishihara

  DOI：10.1016/s0960-894x(96)00248-x

  日期：1996.7

  The joint type of hybrid molecules composed of two pharmacophore moieties taken from histamine H-2 and gastrin receptor antagonists have been designed and synthesized to exhibit dual histamine H-2 and gastrin receptor antagonistic activities. Here we report the importance of spacers as well as binding sites of both pharmacophores for the dual activity. Copyright (C) 1996 Elsevier Science Ltd