(R)-4-(2-oxo-1,2,4,5-tetrahydrobenzo[d][1,3]diazepin-3-yl)-N-(2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)piperidine-1-carboxamide | 820214-52-6

• 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: (R)-4-(2-oxo-1,2,4,5-tetrahydrobenzo[d][1,3]diazepin-3-yl)-N-(2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)piperidine-1-carboxamide
• 英文别名: 4-(2-oxo-4,5-dihydro-1H-1,3-benzodiazepin-3-yl)-N-[(3R)-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-3H-1,4-benzodiazepin-3-yl]piperidine-1-carboxamide
• CAS: 820214-52-6
• 化学式: C₃₂H₃₁F₃N₆O₃
• 分子量: 604.632
• InChiKey: DPKUUAZWPCGLJU-NDEPHWFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  44
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  97.4
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-(4-piperidinyl)-1,3,4,5-tetrahydro-1,3-benzodiazepin-2-one 、 4-nitrophenyl [(3R)-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]carbamate 在 三乙胺 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 生成 (R)-4-(2-oxo-1,2,4,5-tetrahydrobenzo[d][1,3]diazepin-3-yl)-N-(2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)piperidine-1-carboxamide
  参考文献：
  名称：

  Non-peptide calcitonin gene-related peptide receptor antagonists from a benzodiazepinone lead

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2006.02.051

文献信息

• Methods for detecting nucleic acid variations
  申请人：Delgrosso Kathleen

  公开号：US20070111204A1

  公开（公告）日：2007-05-17

  The invention provides methods and diagnostic test kits for detecting target nucleic acid sequence variations in a sample. In particular, a plurality of oligonucleotide probe sets is provided. Each set has a target specific portion and a barcode. The target specific portions of the probes are suitable for ligation together when hybridized adjacent to one another on a corresponding target polynucleotide. The ligated product contains a barcode that binds to a probe attached to a substrate and hence facilitate the capture of the ligated product on the solid support. Detection is carried out with a gold nanoparticle-attached barcode that hybridizes with the barcode on the ligated product.

  该发明提供了一种用于检测样本中目标核酸序列变异的方法和诊断试剂盒。具体来说，提供了多个寡核苷酸探针组。每个组具有一个目标特异部分和一个条形码。当探针的目标特异部分在相应的目标多核苷酸上相邻杂交时，这些探针的目标特异部分适合进行连接。连接的产物包含一个与基质上附着的探针结合的条形码，从而有助于在固体支持上捕获连接的产物。检测是通过与连接的产物上的条形码杂交的金纳米颗粒附着的条形码进行的。
• Benzodiazepine CGRP receptor antagonists
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP1641781B1

  公开（公告）日：2013-03-06
• US7196079B2
  申请人：——

  公开号：US7196079B2

  公开（公告）日：2007-03-27
• 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.