(4S)-1-[1-(4-aminobenzoyl)-2,3-dihydro-1H-indol-6-sulfonyl]-4-phenylimidazolidin-2-one | 503539-19-3

• 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: (4S)-1-[1-(4-aminobenzoyl)-2,3-dihydro-1H-indol-6-sulfonyl]-4-phenylimidazolidin-2-one
• 英文别名: (S)-1-(1-(4-aminobenzoyl)indolin-5-ylsulfonyl)-4-phenylimidazolidin-2-one；JSH-2282；DW2282；(S)-(+)-4-phenyl-1-[N-(4-aminobenzoyl)indoline-5-sulfonyl)-4,5-dihydro-2-imidazolone；DW-2282 free base；(4S)-1-[[1-(4-aminobenzoyl)-2,3-dihydroindol-5-yl]sulfonyl]-4-phenylimidazolidin-2-one
• CAS: 503539-19-3
• 化学式: C₂₄H₂₂N₄O₄S
• 分子量: 462.529
• InChiKey: YZBUIQWOLSBWEX-OAQYLSRUSA-N

物化性质

• 密度：
  1.431±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4S)-1-[1-(4-aminobenzoyl)-2,3-dihydro-1H-indol-6-sulfonyl]-4-phenylimidazolidin-2-one 在 哌啶 、 盐酸 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.25h， 生成 DW2282-Ser*HCl
  参考文献：
  名称：

  Investigation of amino acid conjugates of (S)-1-[1-(4-aminobenzoyl)-2,3-dihydro-1H-indol-6-sulfonyl]-4-phenyl-imidazolidin-2-one (DW2282) as water soluble anticancer prodrugs

  摘要：

  The amino acid-conjugates (1a-k) with eleven amino acids attached to primary amine of (S)-1-[1-(4-aminobenzoyl)-2,3-dihydro-1H-indol-6-sulfonyl]-4-phenyl-imidazolidin-2-one (DW2282, 1) were prepared and studied for their prodrug characteristics and anti-cancer activity against SW620 cell line. All the amino acid derivatives showed not only improved water solubility but also displayed potent anti-cancer activity in vitro. Among these amino acid-conjugates the compounds, DW2282-L-Ala (1b), DW2282-L-Phe (1e), DW2282-L-Leu (1g) and DW2282-L-Met (1h) showed good reconversion within 8 h (104.76%, 84.03%, 95.02% and 78.34%, respectively) to the parent drug in human plasma. In addition, the compounds 1e, 1g and 1j also showed good bioavailability profile along with potent in vivo anticancer activity.

  DOI：

  10.1016/j.ejmech.2014.04.048

文献信息

• Synthesis of Water Soluble Analogs of Arylsulfonylimidazolidinone (JSH-2282)
  作者：Seong-Cheol Bang、Ki-Cheul Lee、Vinay K. Sharma、Niti Sharma、Hyun-Sun Yang、Sang-Hun Jung

  DOI：10.5012/bkcs.2013.34.7.2011

  日期：2013.7.20

  To improve the water solubility of arylsulfonylimidazolidinone (JSH-2282), a potent anti-cancer agent, two urea derivatives, sodium (S)-2-(3-(4-(5-((S)-2-oxo-4-phenylimidazolidin-1-ylsulfonyl)indoline-1-carbonyl)-phenyl)ureido)succinate (2a) and sodium (S)-2-(3-(4-(5-((S)-2-oxo-4-phenylimidazolidin-1-ylsulfonyl)indoline-1-carbonyl)phenyl)ureido)pentanedioate (2b), were synthesized and studied for solubility and anti-cancer activity.

  为提高芳磺酰基咪唑烷酮（JSH-2282）这一高效抗癌药物的水溶性，合成了两种脲类衍生物，即钠盐（S）-2-（3-（4-（5-（（S）-2-氧代-4-苯基咪唑烷-1-磺酰基）吲哚啉-1-羰基）苯基）脲基）琥珀酸酯（2a）和钠盐（S）-2-（3-（4-（5-（（S）-2-氧代-4-苯基咪唑烷-1-磺酰基）吲哚啉-1-羰基）苯基）脲基）戊二酸酯（2b），并研究了它们的水溶性和抗癌活性。
• Arylsulfonylimidazolone derivatives as an antitumor agent
  申请人：Dong Wha Pharm. Ind. Co., Ltd.

  公开号：US05929103A1

  公开（公告）日：1999-07-27

  The present invention relates to a novel arylsulfonylimidazolone derivative represented by the following formula (I) which shows a superior antineoplastic activity in contrast to the known sulfonylurea antitumor agents as well as little side effect: ##STR1## and its pharmaceutically acceptable salt and stereoisomer, in which ----, R.sub.1, and R.sub.2 are as defined in the specification.

  本发明涉及一种新型芳基磺酰基咪唑酮衍生物，其化学式如下(I)，与已知的磺酰脲类抗肿瘤药物相比具有更优异的抗肿瘤活性，且副作用小：##STR1## 以及其药学上可接受的盐和立体异构体，其中----，R.sub.1和R.sub.2在说明书中定义。
• ARYLSULFONYLIMIDAZOLONE DERIVATIVES AS AN ANTITUMOR AGENT
  申请人：DONG WHA PHARMACEUTICAL INDUSTRIAL CO. LTD.

  公开号：EP1021437B1

  公开（公告）日：2001-11-14
• Investigation of amino acid conjugates of (S)-1-[1-(4-aminobenzoyl)-2,3-dihydro-1H-indol-6-sulfonyl]-4-phenyl-imidazolidin-2-one (DW2282) as water soluble anticancer prodrugs
  作者：Ki-Cheul Lee、Eeda Venkateswararao、Vinay Kumar Sharma、Sang-Hun Jung

  DOI：10.1016/j.ejmech.2014.04.048

  日期：2014.6

  The amino acid-conjugates (1a-k) with eleven amino acids attached to primary amine of (S)-1-[1-(4-aminobenzoyl)-2,3-dihydro-1H-indol-6-sulfonyl]-4-phenyl-imidazolidin-2-one (DW2282, 1) were prepared and studied for their prodrug characteristics and anti-cancer activity against SW620 cell line. All the amino acid derivatives showed not only improved water solubility but also displayed potent anti-cancer activity in vitro. Among these amino acid-conjugates the compounds, DW2282-L-Ala (1b), DW2282-L-Phe (1e), DW2282-L-Leu (1g) and DW2282-L-Met (1h) showed good reconversion within 8 h (104.76%, 84.03%, 95.02% and 78.34%, respectively) to the parent drug in human plasma. In addition, the compounds 1e, 1g and 1j also showed good bioavailability profile along with potent in vivo anticancer activity.