tert-butyl 4-(3,5-dibromobenzyloxy)phenylsulfonylcarbamate

• 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: tert-butyl 4-(3,5-dibromobenzyloxy)phenylsulfonylcarbamate
• 英文别名: tert-butyl N-[4-[(3,5-dibromophenyl)methoxy]phenyl]sulfonylcarbamate
• 化学式: C₁₈H₁₉Br₂NO₅S
• 分子量: 521.227
• InChiKey: AKLHNIRTYTZCGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  90.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(3,5-dibromobenzyloxy)phenylsulfonylcarbamate 在 偶氮二甲酸二异丙酯 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 9.0h， 生成 (R)-8-(4-(3,5-dibromobenzyloxy)phenylsulfonyl)-11,11-dimethyl-3,9-dioxo-1-phenyl-2,10-dioxa-4,8-diazadodecane-7-carboxylic acid
  参考文献：
  名称：

  Selective Arylsulfonamide Inhibitors of ADAM-17: Hit Optimization and Activity in Ovarian Cancer Cell Models

  摘要：

  Activated leukocyte cell adhesion molecule (ALCAM) is expressed at the surface of epithelial ovarian cancer (EOC) cells and is released in a soluble form (sALCAM) by ADAM-17-mediated shedding. This process is relevant to EOC cell motility and invasiveness, which is reduced by inhibitors of ADAM-17. In addition, ADAM-17 plays a key role in EGFR signaling and thus may represent a useful target in anticancer therapy. Herein we report our hit optimization effort to identify potent and selective ADAM-17 inhibitors, starting with previously identified inhibitor 1. A new series of secondary sulfonamido-based hydroxamates was designed and synthesized. The biological activity of the newly synthesized compounds was tested in vitro on isolated enzymes and human EOC cell lines. The optimization process led to compound 21, which showed an IC50 of 1.9 nivi on ADAM-17 with greatly increased selectivity. This compound maintained good inhibitory properties on sALCAM shedding in several in vitro assays.

  DOI：

  10.1021/jm4011753
• 作为产物：
  描述：

  sodium p-hydroxybenzenesulfonate 在 4-二甲氨基吡啶 、 草酰氯 、 氨 、 三乙胺 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 异丙醇 、 乙腈 为溶剂， 反应 48.17h， 生成 tert-butyl 4-(3,5-dibromobenzyloxy)phenylsulfonylcarbamate
  参考文献：
  名称：

  Selective Arylsulfonamide Inhibitors of ADAM-17: Hit Optimization and Activity in Ovarian Cancer Cell Models

  摘要：

  Activated leukocyte cell adhesion molecule (ALCAM) is expressed at the surface of epithelial ovarian cancer (EOC) cells and is released in a soluble form (sALCAM) by ADAM-17-mediated shedding. This process is relevant to EOC cell motility and invasiveness, which is reduced by inhibitors of ADAM-17. In addition, ADAM-17 plays a key role in EGFR signaling and thus may represent a useful target in anticancer therapy. Herein we report our hit optimization effort to identify potent and selective ADAM-17 inhibitors, starting with previously identified inhibitor 1. A new series of secondary sulfonamido-based hydroxamates was designed and synthesized. The biological activity of the newly synthesized compounds was tested in vitro on isolated enzymes and human EOC cell lines. The optimization process led to compound 21, which showed an IC50 of 1.9 nivi on ADAM-17 with greatly increased selectivity. This compound maintained good inhibitory properties on sALCAM shedding in several in vitro assays.

  DOI：

  10.1021/jm4011753

文献信息

• Selective Arylsulfonamide Inhibitors of ADAM-17: Hit Optimization and Activity in Ovarian Cancer Cell Models
  作者：Elisa Nuti、Francesca Casalini、Salvatore Santamaria、Marina Fabbi、Grazia Carbotti、Silvano Ferrini、Luciana Marinelli、Valeria La Pietra、Ettore Novellino、Caterina Camodeca、Elisabetta Orlandini、Susanna Nencetti、Armando Rossello

  DOI：10.1021/jm4011753

  日期：2013.10.24

  Activated leukocyte cell adhesion molecule (ALCAM) is expressed at the surface of epithelial ovarian cancer (EOC) cells and is released in a soluble form (sALCAM) by ADAM-17-mediated shedding. This process is relevant to EOC cell motility and invasiveness, which is reduced by inhibitors of ADAM-17. In addition, ADAM-17 plays a key role in EGFR signaling and thus may represent a useful target in anticancer therapy. Herein we report our hit optimization effort to identify potent and selective ADAM-17 inhibitors, starting with previously identified inhibitor 1. A new series of secondary sulfonamido-based hydroxamates was designed and synthesized. The biological activity of the newly synthesized compounds was tested in vitro on isolated enzymes and human EOC cell lines. The optimization process led to compound 21, which showed an IC50 of 1.9 nivi on ADAM-17 with greatly increased selectivity. This compound maintained good inhibitory properties on sALCAM shedding in several in vitro assays.