1,3-dihydro-1-methyl-5-phenyl-3(R,S)-<<(4-nitrophenoxy)carbonyl>amino>-2H-1,4-benzodiazepin-2-one | 136234-80-5

• 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,S)-<<(4-nitrophenoxy)carbonyl>amino>-2H-1,4-benzodiazepin-2-one
• 英文别名: (RS)-1,3-dihydro-1-methyl-3-(p-nitrophenyloxycarbonyl)amino-5-phenyl-2H-1,4-benzodiazepin-2-one；N-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl)-4-nitrophenyl-1-carboxylate；(4-nitrophenyl) N-(1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl)carbamate
• CAS: 136234-80-5
• 化学式: C₂₃H₁₈N₄O₅
• 分子量: 430.42
• InChiKey: BFEXYIQESMHFBL-UHFFFAOYSA-N

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,S)-<<(4-nitrophenoxy)carbonyl>amino>-2H-1,4-benzodiazepin-2-one 生成 (1-Methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-urea
  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：

  1,3-dihydro-1-methyl-3-oximino-5-phenyl-2H-1,4-benzodiazepine-2-one 在 镍 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 三乙胺 为溶剂， 生成 1,3-dihydro-1-methyl-5-phenyl-3(R,S)-<<(4-nitrophenoxy)carbonyl>amino>-2H-1,4-benzodiazepin-2-one
  参考文献：
  名称：

  New benzodiazepine analogs

  摘要：

  公开了一种公式为的苯二氮䓬类似物：它们是胃泌素和胆囊收缩素（CCK）的拮抗剂，具有增强的水溶性，并具有在治疗惊恐症、焦虑症、肿瘤性疾病、治疗疼痛或诱导镇痛，或治疗由药物或酒精滥用引起的戒断反应中有用的特性。

  公开号：

  EP0490590A1

文献信息

• Development of 1,4-benzodiazepine cholecystokinin type B antagonists
  作者：Mark G. Bock、Robert M. DiPardo、Ben E. Evans、Kenneth E. Rittle、Willie L. Whitter、Victor M. Garsky、Kevin F. Gilbert、James L. Leighton、Kenneth L. Carson

  DOI：10.1021/jm00078a018

  日期：1993.12

  4-benzodiazepines, nonpeptidal antagonists of the peptide hormone cholecystokinin (CCK), are described. Derived by reasoned modification of the CCK-A selective 3-carboxamido-1,4-benzodiazepine, MK-329, this paper chronicles the development of potent, orally effective compounds in which selectivity for the CCK-B receptor subtype was achieved. The principal lead structure that emerged from these studied is

  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。
• 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。
• 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.