tert-butyl 4-{4-oxo-6-[3-(4-methoxyphenyl)-prop-1-ynyl]-4H-quinazolin-3-ylmethyl}-benzoate | 660399-56-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: tert-butyl 4-{4-oxo-6-[3-(4-methoxyphenyl)-prop-1-ynyl]-4H-quinazolin-3-ylmethyl}-benzoate
• 英文别名: Tert-butyl 4-[[6-[3-(4-methoxyphenyl)prop-1-ynyl]-4-oxoquinazolin-3-yl]methyl]benzoate；tert-butyl 4-[[6-[3-(4-methoxyphenyl)prop-1-ynyl]-4-oxoquinazolin-3-yl]methyl]benzoate
• CAS: 660399-56-4
• 化学式: C₃₀H₂₈N₂O₄
• 分子量: 480.563
• InChiKey: UEMMJRCOOALKSX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  68.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-{4-oxo-6-[3-(4-methoxyphenyl)-prop-1-ynyl]-4H-quinazolin-3-ylmethyl}-benzoate 在 三氟乙酸 作用下， 反应 0.5h， 生成 4-{6-[3-(4-methoxy-phenyl)-prop-1-ynyl]-4-oxo-4H-quinazoline-3-ylmethyl}-benzoic acid
  参考文献：
  名称：

  Quinazolinones and Pyrido[3,4-d]pyrimidin-4-ones as Orally Active and Specific Matrix Metalloproteinase-13 Inhibitors for the Treatment of Osteoarthritis

  摘要：

  Quinazolinones 8 and pyrido[3,4-d]pyrimidin-4-ones 9 as orally active and specific matrix metalloproteinase-13 inhibitors were discovered for the treatment of osteoarthritis. Starting from a high-through-put screening (HTS) hit thizolopyrimidin-dione 7, we obtained two chemotypes, 8 and 9, using computer-aided drug design (CADD) and methodical structure-activity relationship (SAR) studies. They occupy the unique S1'-specificity pocket and do not bind to the Zn2+ ion. Some pyrido[3,4-d]pyrimidin-4-ones, such as 10a, possess favorable absorption, distribution, metabolism, and elimination (ADME) and safety profiles. 10a effectively prevents cartilage damage in rabbit animal models of osteoarthritis without inducing musculoskeletal side effects when given at extremely high doses to rats.

  DOI：

  10.1021/jm701274v
• 作为产物：
  描述：

  tert-butyl 4-(6-iodo-4-oxoquinazolin-3-ylmethyl)benzoate 、 1-甲氧基-4-(2-丙炔-1-基)苯 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide N,N-二异丙基乙胺 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 24.0h， 生成 tert-butyl 4-{4-oxo-6-[3-(4-methoxyphenyl)-prop-1-ynyl]-4H-quinazolin-3-ylmethyl}-benzoate
  参考文献：
  名称：

  [EN] MATRIX METALLOPROTEINASE INHIBITORS AND METHODS FOR IDENTIFICATION OF LEAD COMPOUNDS
  [FR] INHIBITEURS DE METALLOPROTEINASE MATRICIELLE ET PROCEDES D'IDENTIFICATION DE COMPOSES CHEFS DE FILE

  摘要：

  公开号：

  WO2004014381A2

文献信息

• [EN] MATRIX METALLOPROTEINASE INHIBITORS AND METHODS FOR IDENTIFICATION OF LEAD COMPOUNDS<br/>[FR] INHIBITEURS DE METALLOPROTEINASE MATRICIELLE ET PROCEDES D'IDENTIFICATION DE COMPOSES CHEFS DE FILE
  申请人：WARNER LAMBERT CO

  公开号：WO2004014381A2

  公开（公告）日：2004-02-19
• Quinazolinones and Pyrido[3,4-<i>d</i>]pyrimidin-4-ones as Orally Active and Specific Matrix Metalloproteinase-13 Inhibitors for the Treatment of Osteoarthritis
  作者：Jie Jack Li、Joe Nahra、Adam R. Johnson、Amy Bunker、Patrick O’Brien、Wen-Song Yue、Daniel F. Ortwine、Chiu-Fai Man、Vijay Baragi、Kenneth Kilgore、Richard D. Dyer、Hyo-Kyung Han

  DOI：10.1021/jm701274v

  日期：2008.2.1

  Quinazolinones 8 and pyrido[3,4-d]pyrimidin-4-ones 9 as orally active and specific matrix metalloproteinase-13 inhibitors were discovered for the treatment of osteoarthritis. Starting from a high-through-put screening (HTS) hit thizolopyrimidin-dione 7, we obtained two chemotypes, 8 and 9, using computer-aided drug design (CADD) and methodical structure-activity relationship (SAR) studies. They occupy the unique S1'-specificity pocket and do not bind to the Zn2+ ion. Some pyrido[3,4-d]pyrimidin-4-ones, such as 10a, possess favorable absorption, distribution, metabolism, and elimination (ADME) and safety profiles. 10a effectively prevents cartilage damage in rabbit animal models of osteoarthritis without inducing musculoskeletal side effects when given at extremely high doses to rats.