3-amino-4-(cyclohexylamino)-N-(2-(piperazin-1-yl)ethyl)benzenesulfonamide

• 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-amino-4-(cyclohexylamino)-N-(2-(piperazin-1-yl)ethyl)benzenesulfonamide
• 英文别名: 3-amino-4-(cyclohexylamino)-N-(2-piperazin-1-ylethyl)benzenesulfonamide
• 化学式: C₁₈H₃₁N₅O₂S
• 分子量: 381.542
• InChiKey: ACCJCKBBUPYTID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  108
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-氯-3-硝基苯磺酰氯 在 盐酸 、 10 wt% Pd(OH)2 on carbon 、 氢气 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 39.0h， 生成 3-amino-4-(cyclohexylamino)-N-(2-(piperazin-1-yl)ethyl)benzenesulfonamide
  参考文献：
  名称：

  Discovery of Novel, Drug-Like Ferroptosis Inhibitors with in Vivo Efficacy

  摘要：

  Ferroptosis is an iron-catalyzed, nonapoptotic form of regulated necrosis that results in oxidative lipid damage in cell membranes that can be inhibited by the radical-trapping antioxidant Ferrostatin-1 (Fer-1). Novel inhibitors derived from the Fer-1 scaffold inhibited ferroptosis potently but suffered from solubility issues. In this paper, we report the synthesis of a more stable and readily soluble series of Fer-1 analogues that potently inhibit ferroptosis. The most promising compounds (37, 38, and 39) showed an improved protection compared to Fer-1 against multiorgan injury in mice. No toxicity was observed in mice after daily injection of 39 (UAMC-3203) for 4 weeks. UAMC-3203 inserts rapidly in a phospholipid bilayer in silico, which aligns with the current understanding of the mechanism of action of these compounds. In conclusion, these analogues have superior properties compared to Fer-1, show in vivo efficacy, and represent novel lead compounds with therapeutic potential in relevant ferroptosis-driven disease models.

  DOI：

  10.1021/acs.jmedchem.8b01299

文献信息

• 3-(benzylamino)-4-(cyclohexylamino)-n-(2-(piperazin-1-yl)ethyl)benzenesulfonamide derivatives and related ferrostatin-1 analogues as cell death inhibitors for treating e.g. stroke
  申请人：VIB VZW

  公开号：US11339124B2

  公开（公告）日：2022-05-24

  The present invention relates to 3-(benzylamino)-4-(cyclohexylamino)-N-(2-(piperazin-1-yl)ethyl)benzenesulfonamide derivatives and related ferrostatin-1 (Fer-1) analogues as cell death inhibitors by inhibition of ferroptosis and/or oxytosis for the treatment of stroke, myocardial infarction, diabetes, sepsis, the prevention of transplant rejection, neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, dementia with Lewy bodies and Friedreich's ataxia. The present invention further relates to pharmaceutical compositions of these compounds and discloses methods for making the compounds and the corresponding intermediate.

  本发明涉及 3-(苄基氨基)-4-(环己基氨基)-N-(2-(哌嗪-1-基)乙基)苯磺酰胺衍生物和相关的铁前列素-1（Fer-1）类似物，它们通过抑制铁氧化和/或氧氧化作用而成为细胞死亡抑制剂，用于治疗中风、心肌梗塞、糖尿病、败血症、预防移植排斥反应、神经退行性疾病（包括阿尔茨海默病、帕金森病、肌萎缩侧索硬化症）、心肌梗塞、糖尿病、败血症、预防移植排斥反应、神经退行性疾病，包括阿尔茨海默病、帕金森病、肌萎缩性脊髓侧索硬化症、多发性硬化症、亨廷顿氏病、路易体痴呆症和弗里德里希共济失调症。本发明进一步涉及这些化合物的药物组合物，并公开了制造这些化合物和相应中间体的方法。
• 3-(BENZYLAMINO)-4-(CYCLOHEXYLAMINO)-N-(2-(PIPERAZIN-1-YL)ETHYL)BENZENESULFONAMIDE DERIVATIVES AND RELATED FERROSTATIN-1 ANALOGUES AS CELL DEATH INHIBITORS FOR TREATING E.G. STROKE
  申请人：VIB VZW

  公开号：US20210094909A1

  公开（公告）日：2021-04-01

  The present invention relates to 3-(benzylamino)-4-(cyclohexylamino)-N-(2-(piperazin-1-yl)ethyl)benzenesulfonamide derivatives and related ferrostatin-1 (Fer-1) analogues as cell death inhibitors by inhibition of ferroptosis and/or oxytosis for the treatment of stroke, myocardial infarction, diabetes, sepsis, the prevention of transplant rejection, neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, dementia with Lewy bodies and Friedreich's ataxia. The present invention further relates to pharmaceutical compositions of these compounds and discloses methods for making the compounds and the corresponding intermediate.
• Discovery of Novel, Drug-Like Ferroptosis Inhibitors with in Vivo Efficacy
  作者：Lars Devisscher、Samya Van Coillie、Sam Hofmans、Dries Van Rompaey、Kenneth Goossens、Eline Meul、Louis Maes、Hans De Winter、Pieter Van Der Veken、Peter Vandenabeele、Tom Vanden Berghe、Koen Augustyns

  DOI：10.1021/acs.jmedchem.8b01299

  日期：2018.11.21

  Ferroptosis is an iron-catalyzed, nonapoptotic form of regulated necrosis that results in oxidative lipid damage in cell membranes that can be inhibited by the radical-trapping antioxidant Ferrostatin-1 (Fer-1). Novel inhibitors derived from the Fer-1 scaffold inhibited ferroptosis potently but suffered from solubility issues. In this paper, we report the synthesis of a more stable and readily soluble series of Fer-1 analogues that potently inhibit ferroptosis. The most promising compounds (37, 38, and 39) showed an improved protection compared to Fer-1 against multiorgan injury in mice. No toxicity was observed in mice after daily injection of 39 (UAMC-3203) for 4 weeks. UAMC-3203 inserts rapidly in a phospholipid bilayer in silico, which aligns with the current understanding of the mechanism of action of these compounds. In conclusion, these analogues have superior properties compared to Fer-1, show in vivo efficacy, and represent novel lead compounds with therapeutic potential in relevant ferroptosis-driven disease models.