6-[[4-(benzenesulfonyl)phenyl]methyl-ethylamino]-1H-benzo[cd]indole-2-thione | 143032-70-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 6-[[4-(benzenesulfonyl)phenyl]methyl-ethylamino]-1H-benzo[cd]indole-2-thione
• CAS: 143032-70-6
• 化学式: C₂₆H₂₂N₂O₂S₂
• 分子量: 458.605
• InChiKey: SDFFMXMQAJPGKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  89.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-[[4-(benzenesulfonyl)phenyl]methyl-ethylamino]-1H-benzo[cd]indole-2-thione 在 sodium hydroxide 、 氨 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 为溶剂， 生成 6-N-[[4-(benzenesulfonyl)phenyl]methyl]-6-N-ethylbenzo[cd]indole-2,6-diamine
  参考文献：
  名称：

  Crystal-structure-based design and synthesis of benz[cd]indole-containing inhibitors of thymidylate synthase

  摘要：

  The X-ray crystal-structure-based design, synthesis, and biological activity of a novel family of benz[cd]indole-containing inhibitors of thymidylate synthase (TS) are described. The structure-activity of the lead compound was studied by conceptually dividing the molecule into four regions and independently optimizing the substituents for each region. Combination of favored substituents for each region led to inhibitors with K(i)'s against the human enyzme in the range of 10-20 nM. Thymidine shift experiments suggested that the cytotoxic properties of the best enzyme inhibitors were due to TS targeting in cells. The inhibitors were synthesized from substitued 6-aminobenz[cd]indol-2(1H)-ones by alkylation with both a simple alkyl group and a substituted benzylic portion. The 2,6-diaminobenz[cd]indoles were prepared from the corresponding lactams by conversion to the thiolactam, alkylation to the methylated thiolactam, and then displacement with a substituted or unsubstituted amine.

  DOI：

  10.1021/jm00082a006
• 作为产物：
  描述：

  1-(苯磺酰基)-4-(溴甲基)苯 在 劳森试剂 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 6-[[4-(benzenesulfonyl)phenyl]methyl-ethylamino]-1H-benzo[cd]indole-2-thione
  参考文献：
  名称：

  Crystal-structure-based design and synthesis of benz[cd]indole-containing inhibitors of thymidylate synthase

  摘要：

  The X-ray crystal-structure-based design, synthesis, and biological activity of a novel family of benz[cd]indole-containing inhibitors of thymidylate synthase (TS) are described. The structure-activity of the lead compound was studied by conceptually dividing the molecule into four regions and independently optimizing the substituents for each region. Combination of favored substituents for each region led to inhibitors with K(i)'s against the human enyzme in the range of 10-20 nM. Thymidine shift experiments suggested that the cytotoxic properties of the best enzyme inhibitors were due to TS targeting in cells. The inhibitors were synthesized from substitued 6-aminobenz[cd]indol-2(1H)-ones by alkylation with both a simple alkyl group and a substituted benzylic portion. The 2,6-diaminobenz[cd]indoles were prepared from the corresponding lactams by conversion to the thiolactam, alkylation to the methylated thiolactam, and then displacement with a substituted or unsubstituted amine.

  DOI：

  10.1021/jm00082a006

文献信息

• ANTIPROLIFERATIVE SUBSTITUTED NAPHTHALENE COMPOUNDS
  申请人：AGOURON PHARMACEUTICALS

  公开号：EP0550566A1

  公开（公告）日：1993-07-14
• [EN] ANTIPROLIFERATIVE SUBSTITUTED NAPHTHALENE COMPOUNDS
  申请人：AGOURON PHARMACEUTICALS, INC.

  公开号：WO1992005153A1

  公开（公告）日：1992-04-02

  (EN) The present invention relates to certain naphthalene compounds which inhibit the enzyme thymidylate synthase ('TS'), pharmaceutical compositions containing these cyclic compounds, and the use of these compounds to inhibit TS, including all effects derived from the inhibition of TS. Effects derived from the inhibiton of TS include the inhibition of the growth and proliferation of the cells of higher organisms and of microorganisms, such as yeast and fungi. Such effects include antitumor activity. Processes for the preparation of the naphthalene compounds of the invention are also disclosed. (I) wherein: Z and W are independently nitrogen, sulfur, or substituted or unsubstituted alkylene groups with the proviso that, when either of Z or W is nitrogen or sulfur, the other is a substituted or unsubstituted alkylene group; Ar is a group comprising one or more rings selected from the group consisting of (1) substituted or unsubstituted aryl rings and (2) substituted or unsubstituted heterocyclic rings; X and Y together form a nitrogen-containing, five- or six-membered heterocyclic ring which itself may be substituted or unsubstituted.(FR) Cette invention concerne certains composés de naphtalène qui inhibent l'enzyme de synthase thymidylate ('TS'), des compositions pharmaceutiques renfermant ces composés cycliques, et l'utilisation de ces composés pour inhiber le TS, ainsi que tous les effets dus à l'inhibition du TS. Les effets provenant de l'inhibition du TS comprennent l'inhibition de la croissance et de la prolifération des cellules d'organismes plus évolués et de microorganismes, tels que des levures et des champignons. De tels effets comprennent une activité antitumorale. L'invention concerne également des procédés de préparation des composés au naphtalène décrit dans l'invention, correspondant à la formule (I), dans laquelle Z et W représentent indépendamment azote, soufre, ou des groupes alkylènes substitutés ou non à condition que lorsque Z ou W représente azote ou soufre, l'autre élément représente un groupe alkylène substitué ou non; Ar représente un groupe comprenant un ou plusieurs composés choisis parmi le groupe constitué (1) de composés aryle substitués ou non et (2) de composés hétérocycliques substitutés ou non; X et Y forment ensemble un composé hétérocyclique pentagonal ou hexagonal, renfermant de l'azote qui peut être lui-même substituté ou non.