4-(3-butyl-2-oxoimidazolidin-1-yl)-N-(3,4,5-trimethoxy-phenyl)-benzenesulfonamide | 1422527-85-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 4-(3-butyl-2-oxoimidazolidin-1-yl)-N-(3,4,5-trimethoxy-phenyl)-benzenesulfonamide
• 英文别名: 4-(3-butyl-2-oxoimidazolidin-1-yl)-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide
• CAS: 1422527-85-2
• 化学式: C₂₂H₂₉N₃O₆S
• 分子量: 463.555
• InChiKey: JDBOGILEKJNQDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(3-butyl-2-oxoimidazolidin-1-yl)-N-(3,4,5-trimethoxy-phenyl)-benzenesulfonamide 在 sodium salt 作用下， 以 四氢呋喃 为溶剂， 以90 %的产率得到4-(3-butyl-2-oxoimidazolidin-1-yl)-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide sodium
  参考文献：
  名称：

  4-(3-烷基-2-氧代咪唑啉-1-基)-N-苯基苯磺酰胺盐：新型水溶性抗有丝分裂前药，在乳腺癌细胞中被细胞色素 P450 1A1 选择性生物激活

  摘要：

  4-(3-烷基-2-氧代咪唑烷-1-基)-N-苯基苯磺酰胺 (PAIB-SAs) 是新的前药家族的成员，可被乳腺癌细胞中的细胞色素 P450 1A1 (CYP1A1) 生物激活为有效的 4-( 2-氧代咪唑啉-1-基)-N-苯基苯磺酰胺代谢物 (PIB-SA)。在动物研究中，PAIB-SA 的盖仑制剂和给药的主要问题之一是它们的水溶性差。为了克服这一困难，我们报告了 18 种新的PAIB-SAs Na +、K +和 Li +盐的设计、合成、化学表征、水溶性评估、抗增殖活性和作用机制。我们的结果证明，与不敏感的 MDA-MB-231 和 HaCaT 细胞相比，后者对表达内源 CYP1A1 的 MCF7 和 MDA-MB-468 乳腺癌细胞表现出高度选择性的抗增殖活性。此外，PAIB-SA 盐1 – 18的水溶性 (3.9–9.4 mg/mL) 明显高于中性盐 (< 0.0001 mg/mL)。此外，最有效的

  DOI：

  10.1016/j.bioorg.2023.106820
• 作为产物：
  描述：

  1-(2-氯乙基)-3-苯基脲 在 氯磺酸 、 4-二甲氨基吡啶 、 sodium hydride 作用下， 以 四氢呋喃 、 四氯化碳 、 乙腈 为溶剂， 反应 76.0h， 生成 4-(3-butyl-2-oxoimidazolidin-1-yl)-N-(3,4,5-trimethoxy-phenyl)-benzenesulfonamide
  参考文献：
  名称：

  4-(3-Alkyl-2-oxoimidazolidin-1-yl)-N-phenylbenzenesulfonamides as new antimitotic prodrugs activated by cytochrome P450 1A1 in breast cancer cells

  摘要：

  The role and the importance of the sulfonate moiety in phenyl 4-(2-oxo-3-alkylimidazolidin-1-yl) benzenesulfonates (PAIB-SOs) were assessed using its bioisosteric sulfonamide equivalent leading to new cytochrome P450 1A1 (CYP1A1)-activated prodrugs designated as 4-(3-alkyl-2-oxoimidazolidin-1-yl)-N-phenylbenzenesulfonamides (PAIB-SAs). PAIB-SAs are active in the submicromolar to low micromolar range showing selectivity toward CYP1A1-expressing MCF7 cells as compared to cells devoid of CYP1A1 activity such as MDA-MB-231 and HaCaT cells. The most potent, PAIB-SA 13, bearing a trimethoxyphenyl group on ring B blocks the cell cycle progression in G2/M phase, disrupts the microtubule dynamics and is biotransformed by CYP1A1 into CEU-638, its potent antimicrotuble counterpart. Structure-activity relationships related to PAIB-SOs and PAIB-SAs evidenced that PAIB-SOs and PAIB-SAs are true bioisosteric equivalents fully and selectively activatable by CYP1A-expressing cells into potent antimitotics.

  DOI：

  10.1016/j.bmc.2018.09.001

文献信息

• Substituted 2-Imidazolidinones and 2-Imidazolones and Their Use in the Treatment of Cancer
  申请人：C.-Gaudreault Rene

  公开号：US20140315968A1

  公开（公告）日：2014-10-23

  Compounds of formula (I) wherein R 1 , R 4 , R 8 , X and Y as defined herein are provided as useful for the inhibition of certain types of cancer cells, amongst others, breast cancer cells, or for the manufacture of anti-cancer agents.
• SUBSTITUTED 2-IMIDAZOLIDINONES AND 2-IMIDAZOLONES AND THEIR USE IN THE TREATMENT OF CANCER
  申请人：UNIVERSITÉ LAVAL

  公开号：US20160184270A1

  公开（公告）日：2016-06-30

  Compounds of formula (I) wherein R 1 , R 4 , R 8 , X and Y as defined herein are provided as useful for the inhibition of certain types of cancer cells, amongst others, breast cancer cells, or for the manufacture of anti-cancer agents.
• US9278937B2
  申请人：——

  公开号：US9278937B2

  公开（公告）日：2016-03-08
• US9579306B2
  申请人：——

  公开号：US9579306B2

  公开（公告）日：2017-02-28
• 4-(3-Alkyl-2-oxoimidazolidin-1-yl)-N-phenylbenzenesulfonamides as new antimitotic prodrugs activated by cytochrome P450 1A1 in breast cancer cells
  作者：Atziri Corin Chavez Alvarez、Mitra Zarifi Khosroshahi、Marie-France Côté、Mathieu Gagné-Boulet、Sébastien Fortin

  DOI：10.1016/j.bmc.2018.09.001

  日期：2018.10

  The role and the importance of the sulfonate moiety in phenyl 4-(2-oxo-3-alkylimidazolidin-1-yl) benzenesulfonates (PAIB-SOs) were assessed using its bioisosteric sulfonamide equivalent leading to new cytochrome P450 1A1 (CYP1A1)-activated prodrugs designated as 4-(3-alkyl-2-oxoimidazolidin-1-yl)-N-phenylbenzenesulfonamides (PAIB-SAs). PAIB-SAs are active in the submicromolar to low micromolar range showing selectivity toward CYP1A1-expressing MCF7 cells as compared to cells devoid of CYP1A1 activity such as MDA-MB-231 and HaCaT cells. The most potent, PAIB-SA 13, bearing a trimethoxyphenyl group on ring B blocks the cell cycle progression in G2/M phase, disrupts the microtubule dynamics and is biotransformed by CYP1A1 into CEU-638, its potent antimicrotuble counterpart. Structure-activity relationships related to PAIB-SOs and PAIB-SAs evidenced that PAIB-SOs and PAIB-SAs are true bioisosteric equivalents fully and selectively activatable by CYP1A-expressing cells into potent antimitotics.