{4-oxo-2-[(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethyl)carbamoyl]-3,4,5,6,7,8-hexahydrobenzo[4,5]thieno[2,3-d]pyrimidin-5-yl}acetic acid | 1029688-46-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: {4-oxo-2-[(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethyl)carbamoyl]-3,4,5,6,7,8-hexahydrobenzo[4,5]thieno[2,3-d]pyrimidin-5-yl}acetic acid
• 英文别名: 2-[4-oxo-2-[(3-oxo-4H-1,4-benzoxazin-6-yl)methylcarbamoyl]-5,6,7,8-tetrahydro-3H-[1]benzothiolo[2,3-d]pyrimidin-5-yl]acetic acid
• CAS: 1029688-46-7
• 化学式: C₂₂H₂₀N₄O₆S
• 分子量: 468.49
• InChiKey: JCGIMUBZBSZGII-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  174
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  {4-oxo-2-[(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethyl)carbamoyl]-3,4,5,6,7,8-hexahydrobenzo[4,5]thieno[2,3-d]pyrimidin-5-yl}acetic acid 在 N-甲基吗啉 、 N-羟基-7-氮杂苯并三氮唑 、 氯化铵 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以69%的产率得到5-carbamoylmethyl-4-oxo-3,4,5,6,7,8-hexahydrobenzo[4,5]thieno[2,3-d]pyrimidine-2-carboxylic acid (3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethyl)amide
  参考文献：
  名称：

  Extra Binding Region Induced by Non-Zinc Chelating Inhibitors into the S₁′ Subsite of Matrix Metalloproteinase 8 (MMP-8)

  摘要：

  The mode of binding and the activity of the first two non-zinc chelating, potent, and selective inhibitors of human neutrophil collagenase are reported. The crystal structures of the catalytic domain of MMP-8, respectively complexed with each inhibitor, reveals that both ligands are deeply inserted into the primary specificity subsite S(1)', where they induce a similar conformational change of the surrounding loop that is endowed with the main specificity determinants of MMPs. Accord to this rearrangement, both inhibitors remove the floor of the pocket formed by the Y227 side-chain, rendering available an extra binding region never explored before. The present data show that potent and more selective inhibitors can be obtained by developing ligands able to interact with the selectivity regions of the enzyme rather than with the catalytic zinc ion, which is the common feature of all MMP members.

  DOI：

  10.1021/jm801166j
• 作为产物：
  描述：

  {4-oxo-2-[(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethyl)carbamoyl]-3,4,5,6,7,8-hexahydrobenzo[4,5]thieno[2,3-d]pyrimidin-5-yl}acetic acid ethyl ester 在 lithium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 4.0h， 以80%的产率得到{4-oxo-2-[(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethyl)carbamoyl]-3,4,5,6,7,8-hexahydrobenzo[4,5]thieno[2,3-d]pyrimidin-5-yl}acetic acid
  参考文献：
  名称：

  Extra Binding Region Induced by Non-Zinc Chelating Inhibitors into the S₁′ Subsite of Matrix Metalloproteinase 8 (MMP-8)

  摘要：

  The mode of binding and the activity of the first two non-zinc chelating, potent, and selective inhibitors of human neutrophil collagenase are reported. The crystal structures of the catalytic domain of MMP-8, respectively complexed with each inhibitor, reveals that both ligands are deeply inserted into the primary specificity subsite S(1)', where they induce a similar conformational change of the surrounding loop that is endowed with the main specificity determinants of MMPs. Accord to this rearrangement, both inhibitors remove the floor of the pocket formed by the Y227 side-chain, rendering available an extra binding region never explored before. The present data show that potent and more selective inhibitors can be obtained by developing ligands able to interact with the selectivity regions of the enzyme rather than with the catalytic zinc ion, which is the common feature of all MMP members.

  DOI：

  10.1021/jm801166j

文献信息

• WO2008/63667
  申请人：——

  公开号：——

  公开（公告）日：——
• Heterotricyclic metalloprotease inhibitors
  申请人：Gege Christian

  公开号：US20080207607A1

  公开（公告）日：2008-08-28

  The present invention relates generally to azatriocyclic containing pharmaceutical agents, and in particular, to azatricyclic metalloprotease inhibiting compounds. More particularly, the present invention provides a new class of azatricyclic MMP-3, MMP-8 and/or MMP-13 inhibiting compounds, that exhibit an increased potency and selectivity in relation to currently known MMP-13, MMP-8 and MMP-3 inhibitors.
• Heterotricyclic Metalloprotease Inhibitors
  申请人：Gege Christian

  公开号：US20100087420A1

  公开（公告）日：2010-04-08

  The present invention relates generally to azatriocyclic containing pharmaceutical agents, and in particular, to azatricyclic metalloprotease inhibiting compounds. More particularly, the present invention provides a new class of azatricyclic MMP-3, MMP-8 and/or MMP-13 inhibiting compounds, that exhibit an increased potency and selectivity in relation to currently known MMP-13, MMP-8 and MMP-3 inhibitors.
• US7749996B2
  申请人：——

  公开号：US7749996B2

  公开（公告）日：2010-07-06
• [EN] HETEROTRICYCLIC METALLOPROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE MÉTALLOPROTÉASE HÉTÉROTRICYCLIQUE
  申请人：ALANTOS PHARM HOLDING

  公开号：WO2008063667A1

  公开（公告）日：2008-05-29

  [EN] The present invention relates generally to azatricyclic containing pharmaceutical agents, and in particular, to azatricyclic metalloprotease inhibiting compounds. More particularly, the present invention provides a new class of azatricyclic MMP-3, MMP-8 and/or MMP-13 inhibiting compounds, that exhibit an increased potency and selectivity in relation to currently known MMP-13, MMP-8 and MMP-3 inhibitors.
  [FR] L'invention concerne, de manière générale, des agents pharmaceutiques contenant de l'azatricyclique, et notamment des composés inhibant la métalloprotéase azatricyclique. Cette invention concerne plus particulièrement une nouvelle classe de composés inhibant les MMP-3, MMP-8 et/ou MMP-13 azatricycliques, qui offre une puissance et une sélectivité améliorées par rapport aux inhibiteurs de MMP-13, MMP-8 et MMP-3 actuellement connus.