1,3-dihydro-1-methyl-5-phenyl-3(R)-<<(4-nitrophenoxy)carbonyl>amino>-2H-1,4-benzodiazepin-2-one | 136051-20-2

• 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-methyl-5-phenyl-3(R)-<<(4-nitrophenoxy)carbonyl>amino>-2H-1,4-benzodiazepin-2-one
• 英文别名: (R)-1,3-Dihydro-1-methyl-3-(p-nitrophenyl-oxycarbonyl)amino-5-phenyl-2H-1,4-benzodiazepin-2-one；(R)-1,3-dihydro-1-methyl-3-(p-nitrophenyloxycarbonyl)amino-5-phenyl-2H-1,4-benzodiazepin-2-one；(4-nitrophenyl) N-[(3R)-1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]carbamate
• CAS: 136051-20-2
• 化学式: C₂₃H₁₈N₄O₅
• 分子量: 430.42
• InChiKey: BFEXYIQESMHFBL-NRFANRHFSA-N

物化性质

• 沸点：
  661.5±55.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  32
• 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：
  117
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1,3-dihydro-1-methyl-5-phenyl-3(R)-<<(4-nitrophenoxy)carbonyl>amino>-2H-1,4-benzodiazepin-2-one 以88%的产率得到
  参考文献：
  名称：

  Bock Mark G., DiPardo Robert M., Evans Ben E., Rittle Kenneth E., Whitter+, J. Med. Chem, 36 (1993) N 26, S 4276- 4292

  摘要：

  DOI：
• 作为产物：
  描述：

  (3R)-3-amino-1-methyl-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one 、 对硝基苯基氯甲酸酯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 生成 1,3-dihydro-1-methyl-5-phenyl-3(R)-<<(4-nitrophenoxy)carbonyl>amino>-2H-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。
• 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.

  公开了一种苯二氮䓬类似物的化学式：##STR1##其中：R.sup.3为##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为O、S、HH或NR.sup.15，但有条件限定X.sup.7只能在R.sup.1不是H时为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，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方面有用的特性，还可用于增强吗啡和其他阿片类镇痛药的治疗。
• Benzodiazepine analogs for treating panic syndrome and for directly inducing analgesia
  申请人：MERCK & CO. INC.

  公开号：EP0434364A2

  公开（公告）日：1991-06-26

  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.

  式中的苯二氮卓类似物： 公开了胃泌素和胆囊收缩素（CCK）的拮抗剂，具有治疗惊恐综合征和直接诱导镇痛的特性。
• Non-peptide calcitonin gene-related peptide receptor antagonists from a benzodiazepinone lead
  作者：Theresa M. Williams、Craig A. Stump、Diem N. Nguyen、Amy G. Quigley、Ian M. Bell、Steven N. Gallicchio、C. Blair Zartman、Bang-Lin Wan、Kimberly Della Penna、Priya Kunapuli、Stefanie A. Kane、Ken S. Koblan、Scott D. Mosser、Ruth Z. Rutledge、Christopher Salvatore、John F. Fay、Joseph P. Vacca、Samuel L. Graham

  DOI：10.1016/j.bmcl.2006.02.051

  日期：2006.5

  High-throughput screening of the Merck sample collection identified benzodiazepinone tetralin-spirohydantoin 1 as a CGRP receptor antagonist with micromolar activity. Comparing the structure of 1 with those of earlier peptide-based antagonists such as BIBN 4096 BS, a key hydrogen bond donor-acceptor pharmacophore was hypothesized. Subsequent structure activity studies supported this hypothesis and led to benzodiazepinone piperidinyldihydroquinazolinone 7, CGRP receptor K-i=44 nM and IC50=38 nM. Compound 7 was orally bioavailabile in rats and is a lead in the development of orally bioavailable CGRP antagonists for the treatment of migraine. (C) 2006 Elsevier Ltd. All rights reserved.