4-(dimethylamino)phenyl 4-[3-(2-chloroethyl)ureido]benzenesulfonate | 1328953-82-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(dimethylamino)phenyl 4-[3-(2-chloroethyl)ureido]benzenesulfonate
• 英文别名: [4-(Dimethylamino)phenyl] 4-(2-chloroethylcarbamoylamino)benzenesulfonate
• CAS: 1328953-82-7
• 化学式: C₁₇H₂₀ClN₃O₄S
• 分子量: 397.883
• InChiKey: OLEKDRCSRRNAPS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  96.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(dimethylamino)phenyl 4-[3-(2-chloroethyl)ureido]benzenesulfonate 以 乙腈 为溶剂， 以53%的产率得到4-(dimethylamino)phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonate
  参考文献：
  名称：

  Design, Synthesis, Biological Evaluation, and Structure–Activity Relationships of Substituted Phenyl 4-(2-Oxoimidazolidin-1-yl)benzenesulfonates as New Tubulin Inhibitors Mimicking Combretastatin A-4

  摘要：

  Sixty-one phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates (PIB-SOs) and 13 of their tetrahydro-2-oxopyrimidin-1(2H)-yl analogues (PPB-SOs) were prepared and biologically evaluated. The antiproliferative activities of PIB-SOs on 16 cancer cell lines are in the nanomolar range and unaffected in cancer cells resistant to colchicine, paclitaxel, and vinblastine or overexpressing the P-glycoprotein. None of the PPB-SOs exhibit significant antiproliferative activity. PIB-SOs block the cell cycle progression in the G(2)/M phase and bind to the colchicine-binding site on beta-tubulin leading to cytoskeleton disruption and cell death. Chick chorioallantoic membrane tumor assays show that compounds 36, 44, and 45 efficiently block angiogenesis and tumor growth at least at similar levels as combretastatin A-4 (CA-4) and exhibit low to very low toxicity on the chick embryos. PIB-SOs were subjected to CoMFA and CoMSIA analyses to establish quantitative structure-activity relationships.

  DOI：

  10.1021/jm200488a
• 作为产物：
  描述：

  4-二甲氨基苯酚 在 盐酸 、 铁粉 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 24.25h， 生成 4-(dimethylamino)phenyl 4-[3-(2-chloroethyl)ureido]benzenesulfonate
  参考文献：
  名称：

  Synthesis, Biological Evaluation, and Structure–Activity Relationships of Novel Substituted N-Phenyl Ureidobenzenesulfonate Derivatives Blocking Cell Cycle Progression in S-Phase and Inducing DNA Double-Strand Breaks

  摘要：

  Twenty-eight new substituted N-phenyl ureido-benzenesulfonate (PUB-SO) and 18 N-phenylureidobenzene-sulfonamide (PUB-SA) derivatives were prepared. Several PUB-SOs exhibited antiproliferative activity at the micromolar level against the HT-29, M21, and MCF-7 cell lines and blocked cell cycle progression in S-phase similarly to cisplatin. In addition, PUB-SOs induced histone H2AX (gamma H2AX) phosphorylation, indicating that these molecules induce DNA double-strand breaks. In contrast, PUB-SAs were less active than PUB-SOs and did not block cell cycle progression in S-phase. Finally, PUB-SOs 4 and 46 exhibited potent antitumor activity in HT-1080 fibrosarcoma cells grafted onto chick chorioallantoic membranes, which was similar to cisplatin and combretastatin A-4 and without significant toxicity toward chick embryos. These new compounds are members of a promising new class of anticancer agents.

  DOI：

  10.1021/jm3006492

文献信息

• [EN] SUBSTITUTED 2-IMIDAZOLIDONES AND ANALOGS<br/>[FR] 2-IMIDAZOLIDONES SUBSTITUES ET ANALOGUES
  申请人：UNIV LAVAL

  公开号：WO2011100840A1

  公开（公告）日：2011-08-25

  Compounds of formula (I): wherein R1, R2, R3, R4, R7, R6, R7, R8, R9, A, X and Y as defined herein are provided as useful for the treatment of cancer or for the manufacture of anti-cancer agents.

  式（I）的化合物：其中所述的R1、R2、R3、R4、R7、R6、R7、R8、R9、A、X和Y如本文所定义的那样，被提供为用于治疗癌症或用于制造抗癌药物。
• [EN] ALKYLUREA DERIVATIVES ACTIVE AGAINST CANCER CELLS<br/>[FR] DÉRIVÉS D'ALKYLURÉE ACTIFS CONTRE LES CELLULES CANCÉREUSES
  申请人：UNIV LAVAL

  公开号：WO2012142698A1

  公开（公告）日：2012-10-26

  Compounds of formula (I) : wherein A, m, n, R1, X, Y, R2, R3, R4, R5 and R6, as defined herein are provided as useful for the treatment of cancer or for the manufacture of anti-cancer agents.

  化合物的化学式（I）：其中A、m、n、R1、X、Y、R2、R3、R4、R5和R6的定义如下，在此处被提供作为治疗癌症或制造抗癌药物的有用化合物。
• SUBSTITUTED 2-IMIDAZOLIDONES AND ANALOGS
  申请人：Université Laval

  公开号：EP2536693A1

  公开（公告）日：2012-12-26
• US9034888B2
  申请人：——

  公开号：US9034888B2

  公开（公告）日：2015-05-19
• Design, Synthesis, Biological Evaluation, and Structure–Activity Relationships of Substituted Phenyl 4-(2-Oxoimidazolidin-1-yl)benzenesulfonates as New Tubulin Inhibitors Mimicking Combretastatin A-4
  作者：Sébastien Fortin、Lianhu Wei、Emmanuel Moreau、Jacques Lacroix、Marie-France Côté、Éric Petitclerc、Lakshmi P. Kotra、René C.-Gaudreault

  DOI：10.1021/jm200488a

  日期：2011.7.14

  Sixty-one phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates (PIB-SOs) and 13 of their tetrahydro-2-oxopyrimidin-1(2H)-yl analogues (PPB-SOs) were prepared and biologically evaluated. The antiproliferative activities of PIB-SOs on 16 cancer cell lines are in the nanomolar range and unaffected in cancer cells resistant to colchicine, paclitaxel, and vinblastine or overexpressing the P-glycoprotein. None of the PPB-SOs exhibit significant antiproliferative activity. PIB-SOs block the cell cycle progression in the G(2)/M phase and bind to the colchicine-binding site on beta-tubulin leading to cytoskeleton disruption and cell death. Chick chorioallantoic membrane tumor assays show that compounds 36, 44, and 45 efficiently block angiogenesis and tumor growth at least at similar levels as combretastatin A-4 (CA-4) and exhibit low to very low toxicity on the chick embryos. PIB-SOs were subjected to CoMFA and CoMSIA analyses to establish quantitative structure-activity relationships.