ethyl 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoate | 934813-50-0

• 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: ethyl 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoate
• CAS: 934813-50-0
• 化学式: C₁₉H₂₄N₂O₅S
• 分子量: 392.476
• InChiKey: AVSUTJDVCDDYAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  正丁醛 、 ethyl 3-amino-4-phenoxy-5-sulfamoylbenzoate 在 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以70%的产率得到ethyl 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoate
  参考文献：
  名称：

  Discovery of a Small Molecule Drug Candidate for Selective NKCC1 Inhibition in Brain Disorders

  摘要：

  Aberrant expression ratio of Cl- transporters, NKCC1 and KCC2, is implicated in several brain conditions. NKCC1 inhibition by the FDA-approved diuretic drug, bumetanide, rescues core symptoms in rodent models and/or clinical trials with patients. However, bumetanide has a strong diuretic effect due to inhibition of the kidney Cl- transporter NKCC2, creating critical drug compliance issues and health concerns, Here, we report the discovery of a new chemical class of selective NKCC1 inhibitors and the lead drug candidate ARN23746. ARN23746 restores the physiological intracellular Cl- in murine Down syndrome neuronal cultures, has excellent solubility and metabolic stability, and displays no issues with off-target activity vitro. ARN23746 recovers core symptoms in mouse models of Down syndrome and autism, with no diuretic effect, nor overt toxicity upon chronic treatment in adulthood. ARN23746 is ready for advanced preclinical/manufacturing studies toward the first sustainable therapeutics for the neurological conditions characterized by impaired Cl- homeostasis.

  DOI：

  10.1016/j.chempr.2020.06.017

文献信息

• WO2019193159A5
  申请人：——

  公开号：WO2019193159A5

  公开（公告）日：2022-04-12
• BUMETANIDE DERIVATIVES FOR THE THERAPY OF HYPERHIDROSIS
  申请人：ZILENTIN AG

  公开号：EP3774763A1

  公开（公告）日：2021-02-17
• ANALOGS AND PRODRUGS OF BUMETANIDE; COMPOSITIONS AND METHODS OF USE
  申请人：HOCHMAN Daryl W.

  公开号：US20140066504A1

  公开（公告）日：2014-03-06

  Novel analogs and prodrugs of the loop diuretic bumetanide are described. Pharmaceutical compositions containing bumetanide analogs and prodrugs are also described. These analogs and prodrugs are particularly useful for the treatment and/or prophylaxis of conditions that involve the NKCC cotransporter family (NKCC1 and NKCC2), or the KCC cotransporter family (KCC1, KCC2, KCC3, KCC4), or GABAa receptors. Such conditions include, but are not limited to anxiety disorders, epilepsy, migraine, non-epileptic seizures, sleep disorders, obesity, eating disorders, autism, depression, edema, glaucoma, stroke, ischemia, neuropathic pain, addictive disorders, schizophrenia, psychosis, and tinnitus.
• US3991097A
  申请人：——

  公开号：US3991097A

  公开（公告）日：1976-11-09
• [EN] SULFAMOYLBENZENE DERIVATIVE AND DRUG APPLICATION<br/>[FR] DÉRIVÉ DE SULFAMOYLBENZÈNE ET APPLICATION DE MÉDICAMENT
  申请人：TORAY INDUSTRIES

  公开号：WO2014157635A1

  公开（公告）日：2014-10-02

  　本発明は、脳中への移行性が高く、てんかんの発症部位である脳中でブメタニドに変換されて薬理効果を発揮する医薬を提供することを目的としている。本発明は、下記一般式（Ｉ）で示されるスルファモイルベンゼン誘導体又はその薬学的に許容される塩を提供する。