2-amino-4-ethoxycarbonylmethyl-4,5,6,7-tetrahydrobenz[b]thiophene-3-carboxylic acid ethyl ester | 1029689-53-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 2-amino-4-ethoxycarbonylmethyl-4,5,6,7-tetrahydrobenz[b]thiophene-3-carboxylic acid ethyl ester
• 英文别名: ethyl 2-amino-4-ethoxycarbonylmethyl-4,5,6,7-tetrahydrobenz[b]thiophene-3-carboxylate；Ethyl 2-amino-4-(2-ethoxy-2-oxoethyl)-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate
• CAS: 1029689-53-9
• 化学式: C₁₅H₂₁NO₄S
• 分子量: 311.402
• InChiKey: HFCIWIAMSADOKD-UHFFFAOYSA-N

物化性质

• 沸点：
  448.0±45.0 °C(predicted)
• 密度：
  1.214±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-amino-4-ethoxycarbonylmethyl-4,5,6,7-tetrahydrobenz[b]thiophene-3-carboxylic acid ethyl ester 、 氰基甲酸乙酯 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 以27%的产率得到5-ethoxycarbonylmethyl-4-oxo-3,4,5,6,7,8-hexahydrobenzo[4,5]thieno[2,3-d]pyridmidine-2-carboxylic acid ethyl ester
  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：

  cyano-(2-ethoxycarbonylmethyl-cyclohexylidene)acetic acid ethyl ester 在 sulfur 、 二乙胺 作用下， 以 甲醇 为溶剂， 反应 4.0h， 生成 2-amino-4-ethoxycarbonylmethyl-4,5,6,7-tetrahydrobenz[b]thiophene-3-carboxylic acid ethyl ester
  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

• Characterization of a selective inhibitor for matrix metalloproteinase-8 (MMP-8)
  作者：Derong Ding、Katerina Lichtenwalter、Hualiang Pi、Shahriar Mobashery、Mayland Chang

  DOI：10.1039/c4md00172a

  日期：——

  MMP-8 has been implicated in various diseases. Selective MMP-8 inhibitors are needed to ascertain the role of this enzyme. We synthesized two inhibitors reported previously as selective for MMP-8. Compound 1 selectively inhibited MMP-8 and MMP-13; compound 2 was a potent broad-spectrum inhibitor, notwithstanding that it is used as a selective one.

  MMP-8与多种疾病有关。需要选择性的MMP-8抑制剂来确定这种酶的作用。我们合成了两种先前报道的对MMP-8具有选择性的抑制剂。化合物1选择性抑制MMP-8和MMP-13；化合物2是有效的广谱抑制剂，尽管它被用作选择性抑制剂。
• 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.