4-[[[((3,5-二甲基苯基)氨基]羰基]氨基]苯基氨基磺酸酯 | 1330061-67-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-[[[((3,5-二甲基苯基)氨基]羰基]氨基]苯基氨基磺酸酯
• 英文名称: 4-[(3,5-dimethylphenyl)ureido]phenyl sulfamate
• 英文别名: 4-(3'-(3'',5''-dimethylphenyl)ureido)phenyl sulfamate；BO546；S4；[4-[(3,5-dimethylphenyl)carbamoylamino]phenyl] sulfamate
• CAS: 1330061-67-0
• 化学式: C₁₅H₁₇N₃O₄S
• 分子量: 335.384
• InChiKey: HGVHSNXRZYOTPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-(3,5-dimethylphenyl)-3-(4-hydroxyphenyl)urea 在 氨基磺酰氯 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 以89%的产率得到4-[[[((3,5-二甲基苯基)氨基]羰基]氨基]苯基氨基磺酸酯
  参考文献：
  名称：

  Antimetastatic Effect of Sulfamate Carbonic Anhydrase IX Inhibitors in Breast Carcinoma Xenografts

  摘要：

  A panel of compounds belonging to the underexposed sulfamate class of carbonic anhydrase (CA, EC 4.2.1.1) inhibitors was generated that displayed high specificity at nanomolar levels for the tumor-associated CA IX/XII isoforms. Three of the specific CA IX/XII inhibitors showed a positive response in in vitro assays for tumor cell migration and spreading. One of them, 4-(3'-(3 '',5 ''-dimethylphenyl)-ureido)phenyl sulfamate (S4), was taken forward into the orthotopic MDA-MB-231 (breast carcinoma) model in mice. Treatment with a 10 mg/kg maintenance dosage of S4 given daily on a "5 days on, 2 days off" regimen reduced metastatic tumor burden in the lung while not affecting primary tumor growth or mouse condition. CA inhibitors of the sulfamate class specifically targeting the tumor-associated isoforms are potential candidates in antimetastatic therapy.

  DOI：

  10.1021/jm300529u

文献信息

• CARBONIC ANHYDRASE INHIBITORS
  申请人：Ebbesen Peter

  公开号：US20130053392A1

  公开（公告）日：2013-02-28

  A carbonic anhydrase IX (CA IX) inhibitor which comprises a compound of general formula: R—NH—CX—NH—(CH 2 ) n —Ar-Q-SO 2 —NH 2 or a pharmaceutically-acceptable salt, derivative or prodrug thereof; wherein n=0, 1 or 2; Q is O or NH; X is O or S; and R comprises an organic substituent group.

  一种碳酸酐酶IX（CA IX）抑制剂，包括一种一般化学式为：R—NH—CX—NH—（CH2）n—Ar-Q-SO2—NH2的化合物或其药用可接受的盐、衍生物或前药；其中n=0、1或2；Q为O或NH；X为O或S；R包括一个有机取代基。
• Ureido-substituted sulfamates show potent carbonic anhydrase IX inhibitory and antiproliferative activities against breast cancer cell lines
  作者：Jean-Yves Winum、Fabrizio Carta、Carol Ward、Peter Mullen、David Harrison、Simon P. Langdon、Alessandro Cecchi、Andrea Scozzafava、Ian Kunkler、Claudiu T. Supuran

  DOI：10.1016/j.bmcl.2012.05.083

  日期：2012.7

  A series of 50 sulfamates were obtained by reacting 4-aminophenol with isocyanates followed by sulfamoylation. Most of the new compounds were nanomolar inhibitors of the tumor-associated carbonic anhydrase (CA, EC 4.2.1.1) isoforms IX and XII, whereas they inhibited less cytosolic offtarget isoforms CA I and II. Some of these sulfamates showed significant antiproliferative activity in several breast cancer cell lines, such as SKBR3, MCF10A, ZR75/1, MDA-MB-361 and MCF7, constituting interesting anticancer leads. (C) 2012 Elsevier Ltd. All rights reserved.
• Antimetastatic Effect of Sulfamate Carbonic Anhydrase IX Inhibitors in Breast Carcinoma Xenografts
  作者：Roben G. Gieling、Muhammad Babur、Lupti Mamnani、Natalie Burrows、Brian A. Telfer、Fabrizio Carta、Jean-Yves Winum、Andrea Scozzafava、Claudiu T. Supuran、Kaye J. Williams

  DOI：10.1021/jm300529u

  日期：2012.6.14

  A panel of compounds belonging to the underexposed sulfamate class of carbonic anhydrase (CA, EC 4.2.1.1) inhibitors was generated that displayed high specificity at nanomolar levels for the tumor-associated CA IX/XII isoforms. Three of the specific CA IX/XII inhibitors showed a positive response in in vitro assays for tumor cell migration and spreading. One of them, 4-(3'-(3 '',5 ''-dimethylphenyl)-ureido)phenyl sulfamate (S4), was taken forward into the orthotopic MDA-MB-231 (breast carcinoma) model in mice. Treatment with a 10 mg/kg maintenance dosage of S4 given daily on a "5 days on, 2 days off" regimen reduced metastatic tumor burden in the lung while not affecting primary tumor growth or mouse condition. CA inhibitors of the sulfamate class specifically targeting the tumor-associated isoforms are potential candidates in antimetastatic therapy.