3-(3-(4-bromophenylsulfanyl)-2-oxopropyl)-5,5-dimethylimidazolidine-2,4-dione | 220615-61-2

• 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: 3-(3-(4-bromophenylsulfanyl)-2-oxopropyl)-5,5-dimethylimidazolidine-2,4-dione
• 英文别名: 1-(4-bromophenylthio)-3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-propanone；3-[3-(4-bromophenyl)sulfanyl-2-oxopropyl]-5,5-dimethylimidazolidine-2,4-dione
• CAS: 220615-61-2
• 化学式: C₁₄H₁₅BrN₂O₃S
• 分子量: 371.255
• InChiKey: MHXVXNFOILEVLQ-UHFFFAOYSA-N

物化性质

• 密度：
  1.57±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  91.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(3-(4-bromophenylsulfanyl)-2-oxopropyl)-5,5-dimethylimidazolidine-2,4-dione 在 四(三苯基膦)钯 吡啶 、 盐酸 、 sodium hydroxide 、 吡啶硼烷 、 盐酸羟胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙二醇二甲醚 、 乙醇 为溶剂， 反应 24.0h， 生成 3-[2-Hydroxyamino-3-(4'-trifluoromethyl-biphenyl-4-ylsulfanyl)-propyl]-5,5-dimethyl-imidazolidine-2,4-dione
  参考文献：
  名称：

  Phenoxyphenyl Sulfone N-Formylhydroxylamines (Retrohydroxamates) as Potent, Selective, Orally Bioavailable Matrix Metalloproteinase Inhibitors

  摘要：

  A novel series of sulfone N-formylhydroxylamines (retrohydroxamates) have been investigated as matrix metalloproteinases (MMP) inhibitors. The substitution of the ether linkage of ABT-770 (5) with a sulfone group 13a led to a substantial increase in activity against MMP-9 but was accompanied by a loss of selectivity for inhibition of MMP-2 and -9 over MMP-1 and diminished oral exposure. Replacement of the biphenyl P1' substituent with a phenoxyphenyl group provided compounds that are highly selective for inhibition of MMP-2 and -9 over MMP-1. Optimization of the substituent adjacent to the retrohydroxamate center in this series led to the clinical candidate ABT-518 (6), a highly potent, selective, orally bioavailable MMP inhibitor that has been shown to significantly inhibit tumor growth in animal cancer models.

  DOI：

  10.1021/jm0103920
• 作为产物：
  描述：

  4-溴苯硫酚 、 3-(3-bromo-2-oxopropyl)-5,5-dimethylimidazolidine-2,4-dione 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 3-(3-(4-bromophenylsulfanyl)-2-oxopropyl)-5,5-dimethylimidazolidine-2,4-dione
  参考文献：
  名称：

  Phenoxyphenyl Sulfone N-Formylhydroxylamines (Retrohydroxamates) as Potent, Selective, Orally Bioavailable Matrix Metalloproteinase Inhibitors

  摘要：

  A novel series of sulfone N-formylhydroxylamines (retrohydroxamates) have been investigated as matrix metalloproteinases (MMP) inhibitors. The substitution of the ether linkage of ABT-770 (5) with a sulfone group 13a led to a substantial increase in activity against MMP-9 but was accompanied by a loss of selectivity for inhibition of MMP-2 and -9 over MMP-1 and diminished oral exposure. Replacement of the biphenyl P1' substituent with a phenoxyphenyl group provided compounds that are highly selective for inhibition of MMP-2 and -9 over MMP-1. Optimization of the substituent adjacent to the retrohydroxamate center in this series led to the clinical candidate ABT-518 (6), a highly potent, selective, orally bioavailable MMP inhibitor that has been shown to significantly inhibit tumor growth in animal cancer models.

  DOI：

  10.1021/jm0103920

文献信息

• Reverse hydroxamate inhibitors of matrix metalloproteinases
  申请人：——

  公开号：US20020007060A1

  公开（公告）日：2002-01-17

  Compounds having the formula 1 are matrix metalloproteinase inhibitors. Also disclosed are matrix metalloproteinase-inhibiting compositions and methods of inhibiting matrix metalloproteinase in a mammal.

  具有公式1的化合物是基质金属蛋白酶抑制剂。还披露了基质金属蛋白酶抑制剂组合物和在哺乳动物中抑制基质金属蛋白酶的方法。
• N-HYDROXYFORMAMIDE DERIVATIVES AS INHIBITORS OF MATRIX METALLOPROTEINASES
  申请人：Abbott Laboratories

  公开号：EP1001930B1

  公开（公告）日：2002-12-04
• US6235786B1
  申请人：——

  公开号：US6235786B1

  公开（公告）日：2001-05-22
• US6294573B1
  申请人：——

  公开号：US6294573B1

  公开（公告）日：2001-09-25
• [EN] REVERSE HYDROXAMATE INHIBITORS OF MATRIX METALLOPROTEINASES<br/>[FR] INHIBITEURS D'HYDROXAMATES INVERSES DE METALLOPROTEINASES MATRICIELLES
  申请人：——

  公开号：WO1999006361A2

  公开（公告）日：1999-02-11

  [EN] Compounds having formula (I) are matrix metalloproteinase inhibitors. Also disclosed are matrix metalloproteinase-inhibiting compositions and methods of inhibiting matrix metalloproteinase in a mammal.
  [FR] La présente invention concerne des composés inhibiteurs de métalloprotéinase représentés par la formule générale (I). La présente invention concerne également des compositions et des procédés permettant d'inhiber une métalloprotéinase matricielle chez un mammifère.