2,4-二氯-N-(异丙基)-N-[2-[(异丙基)氨基]乙基]苯磺酰胺 | 946387-07-1

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 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: 2,4-二氯-N-(异丙基)-N-[2-[(异丙基)氨基]乙基]苯磺酰胺
• 英文名称: 2,4-Dichloro-N-isopropyl-N-(2-isopropylaminoethyl)benzenesulfonamide
• 英文别名: 2,4-dichloro-N-propan-2-yl-N-[2-(propan-2-ylamino)ethyl]benzenesulfonamide
• CAS: 946387-07-1
• 化学式: C₁₄H₂₂Cl₂N₂O₂S
• 分子量: 353.3
• InChiKey: IHYZMEAZAIFMTN-UHFFFAOYSA-N

物化性质

• 溶解度：
  二甲基亚砜：>20mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  57.8
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性

RN-1734 (TRPV4 Antagonist I) 是一种选择性的 transient receptor potential vanilloid 4 (TRPV4) 拮抗剂，对于 hTRPV4、mTRPV4 和 rTRPV4 的 IC50 值分别为 2.3 μM、5.9 μM 和 3.2 μM。RN-1734 在不改变 olig2 阳性细胞数量的情况下，可减轻脱髓鞘作用并抑制神经胶质活化以及抑制 tumor necrosis factor α (TNF-α) 和 interleukin 1β (IL-1β) 的产生。

靶点

Target	Value
TNF-α
IL-1β
hTRPV4 (Cell-free assay)	2.3 μM
rTRPV4 (Cell-free assay)	3.2 μM
mTRPV4 (Cell-free assay)	5.9 μM

体外研究

RN-1734 (27 小时，浓度：10 μM) 可逆转由 CM (LPS 激活的小胶质细胞组) 引起的少突胶质细胞凋亡率增加，并缓解 CM 所诱导的 CNP 减少。

细胞凋亡分析

• 细胞系: 小胶质细胞
• 孵育时间: 27 小时
• 浓度: 10 μM
• 结果: 显著减少 cleaved-caspase 3 阳性细胞的比例。

蛋白印迹分析

• 细胞系: 小胶质细胞
• 孵育时间: 27 小时
• 浓度: 10 μM
• 结果: 缓解 LPS 诱导的 CNP 减少。

体内研究

RN-1734 (通过微量注射泵每日给予，剂量：0.5 μl，共五周) 显著逆转了棉酚 (CPZ) 引起的髓鞘减少并改善了小鼠的髓鞘化程度。

实验动物模型

• 动物模型: CPZ 引起的髓鞘损伤 C57BL/6 雄性小鼠
• 剂量: 0.5 μl（10 μM 溶于 5% DMSO 和 0.9% NaCl 中）
• 给药方式: 微量注射泵，持续五周
• 结果: 显著逆转了棉酚引起的 CNP 蛋白减少并改善了髓鞘化。

文献信息

• Fibrous Structures Comprising Sensates
  申请人：The Procter & Gamble Company

  公开号：US20180280562A1

  公开（公告）日：2018-10-04

  Fibrous structures, for example sanitary tissue products, such as toilet tissue, containing one or more sensates, more particularly one or more TRPM8 receptor triggering agents, a sensate composition, for example surface softening composition, comprising one or more TRPM8 receptor triggering agents, and methods for making same are provided.
• USE OF TRPV4 ANTAGONISTS TO AMELIORATE HYDROCEPHALUS AND RELATED MATERIALS AND METHODS
  申请人：Indiana University Research and Technology Corporation

  公开号：US20190262350A1

  公开（公告）日：2019-08-29

  The present disclosure provides uses of TRPV4 antagonists in the treatment or prevention of hydrocephalus symptoms, also known as hydrocephaly, including hydrocephalus as a result of any structural defect, any metabolic defect, any injury (direct force to the head, indirect force to the head, shock waves, pressure changes, etc.), any insult (microbial, chemical, toxins, allergic reactions or other inflammatory process, or other pathology, e.g. cancer, benign tumor, etc.). Related materials and methods are also provided herein.
• Methods for Treating Hydrocephalus
  申请人：Indian University Research and Technology Corporation

  公开号：US20200085767A1

  公开（公告）日：2020-03-19

  Methods for inhibiting transepithelial ion transport, inhibiting hydrocephalic development, and for treating hydrocephalus are disclosed herein. The methods include administering a potassium channel inhibitor to the individual. In one particular embodiment, the individual is administered the calcium-activated potassium channel inhibitor, fluoxetine.
• [EN] METHODS FOR TREATING HYDROCEPHALUS<br/>[FR] PROCÉDÉS DE TRAITEMENT DE L'HYDROCÉPHALIE
  申请人：UNIV INDIANA RES & TECH CORP

  公开号：WO2018119356A1

  公开（公告）日：2018-06-28

  Methods for inhibiting transepithelial ion transport, inhibiting hydrocephalic development, and for treating hydrocephalus are disclosed herein. The methods include administering a potassium channel inhibitor to the individual. In one particular embodiment, the individual is administered the calcium-activated potassium channel inhibitor, fluoxetine.
• [EN] COMPOSITION FOR PREVENTING OR TREATING SPINAL CORD INJURY, COMPRISING TRPV4 ANTAGONIST<br/>[FR] COMPOSITION POUR PRÉVENIR OU TRAITER DES LÉSIONS DE LA MOELLE ÉPINIÈRE, COMPRENANT UN ANTAGONISTE DE TRPV4<br/>[KO] TRPV4 길항제를 포함하는 척수 손상 예방 또는 치료용 조성물
  申请人：SUNGKWANG MEDICAL FOUND

  公开号：WO2021015342A1

  公开（公告）日：2021-01-28

  본 발명은 TRPV4 길항제(transient receptor potential vanilloid 4 antagonist antagonist)를 포함하는 척수 손상 예방 또는 치료용 조성물에 관한 것이다. 본 발명에 따른 TRPV4 길항제를 유효성분으로 포함하는 척수 손상 또는 치료용 약학적 조성물은 척수 손상에 있어 환자에게 특히 고통스러운 신경병증성 통증을 억제하고, 염증반응을 억제할 수 있으며, 글루타메이트 독성을 억제함으로써 척수 손상 치료제로 활용 가능성이 높다.