(R,S)-N-(1-isopropyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-4-(2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxamide | 820214-30-0

• 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,S)-N-(1-isopropyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-4-(2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxamide
• 英文别名: 4-(2-oxo-1,4-dihydroquinazolin-3-yl)-N-(2-oxo-5-phenyl-1-propan-2-yl-3H-1,4-benzodiazepin-3-yl)piperidine-1-carboxamide
• CAS: 820214-30-0
• 化学式: C₃₂H₃₄N₆O₃
• 分子量: 550.66
• InChiKey: BWLUJBRNLJVDMS-UHFFFAOYSA-N

物化性质

• 沸点：
  862.8±65.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  41
• 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：
  4

反应信息

• 作为反应物：
  描述：

  (R,S)-N-(1-isopropyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-4-(2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxamide 、 碘甲烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-(1-methyl-2-oxo-4H-quinazolin-3-yl)-N-(2-oxo-5-phenyl-1-propan-2-yl-3H-1,4-benzodiazepin-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
• 作为产物：
  描述：

  、 3-(哌啶-4-基)-3,4-二氢喹唑啉-2(1H)-酮 在 三乙胺 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 生成 (R,S)-N-(1-isopropyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-4-(2-oxo-1,2-dihydroquinazolin-3(4H)-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

• 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.