3,4-dichloro-N-(2-hydroxy-2-methylpropyl)benzenesulfonamide | 1216469-17-8

• 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: 3,4-dichloro-N-(2-hydroxy-2-methylpropyl)benzenesulfonamide
• CAS: 1216469-17-8
• 化学式: C₁₀H₁₃Cl₂NO₃S
• mdl: MFCD14870995
• 分子量: 298.19
• InChiKey: VIMSYIABMUFZCR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  74.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2R)-2-[(S)-azido(phenyl)methyl]oxirane 、 3,4-dichloro-N-(2-hydroxy-2-methylpropyl)benzenesulfonamide 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 异丙醇 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  Discovery of Orally Active Hydroxyethylamine Based SPPL2a Inhibitors

  摘要：

  SPPL2a (Signal Peptide Peptidase Like 2a) is an intramembrane aspartyl protease engaged in the function of B-cells and dendritic cells. Despite being an attractive target for modulation of the immune system, selective SPPL2a inhibitors are barely described in the literature. Recently, we have disclosed a selective, small molecular weight agent SPL-707 which confirmed that pharmacological inhibition of SPPL2a leads to the accumulation of its substrate CD74/p8 and as a consequence to a reduction in the number of B-cells as well as myeloid dendritic cells in mice. In this paper we describe the discovery of novel hydroxyethylamine based SPPL2a inhibitors. Starting from a rather lipophilic screening hit, several iterative optimization cycles allowed for its transformation into a highly potent and selective compound 15 (SPL-410) which inhibited in vivo CD74/p8 fragment processing in mice at 10 mg/kg oral dose.

  DOI：

  10.1021/acsmedchemlett.9b00044

文献信息

• Discovery of Orally Active Hydroxyethylamine Based SPPL2a Inhibitors
  作者：Juraj Velcicky、Casey J. N. Mathison、Victor Nikulin、Daniel Pflieger、Robert Epple、Mihai Azimioara、Christopher Cow、Pierre-Yves Michellys、Pascal Rigollier、Daniel R. Beisner、Ursula Bodendorf、Danilo Guerini、Bo Liu、Ben Wen、Samantha Zaharevitz、Trixi Brandl

  DOI：10.1021/acsmedchemlett.9b00044

  日期：2019.6.13

  SPPL2a (Signal Peptide Peptidase Like 2a) is an intramembrane aspartyl protease engaged in the function of B-cells and dendritic cells. Despite being an attractive target for modulation of the immune system, selective SPPL2a inhibitors are barely described in the literature. Recently, we have disclosed a selective, small molecular weight agent SPL-707 which confirmed that pharmacological inhibition of SPPL2a leads to the accumulation of its substrate CD74/p8 and as a consequence to a reduction in the number of B-cells as well as myeloid dendritic cells in mice. In this paper we describe the discovery of novel hydroxyethylamine based SPPL2a inhibitors. Starting from a rather lipophilic screening hit, several iterative optimization cycles allowed for its transformation into a highly potent and selective compound 15 (SPL-410) which inhibited in vivo CD74/p8 fragment processing in mice at 10 mg/kg oral dose.