3-(dimethylsulfamoyl)-4-fluorobenzoic acid | 381229-72-7

• 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-(dimethylsulfamoyl)-4-fluorobenzoic acid
• CAS: 381229-72-7
• 化学式: C₉H₁₀FNO₄S
• mdl: MFCD09040991
• 分子量: 247.247
• InChiKey: SFRDRLYPUDGRAQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(dimethylsulfamoyl)-4-fluorobenzoic acid 在 哌啶 、 manganese(IV) oxide 、 草酰氯 、 硼烷 、 potassium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 21.0h， 生成
  参考文献：
  名称：

  Discovery of Novel p-Arylthio Cinnamides as Antagonists of Leukocyte Function-Associated Antigen-1/Intercellular Adhesion Molecule-1 Interaction. 4. Structure−Activity Relationship of Substituents on the Benzene Ring of the Cinnamide

  摘要：

  We have shown that p-arylthio cinnamides can inhibit the interaction of LFA-1 and ICAM-1, which is involved in cell adhesion and the inflammatory process. We now show that 2,3-disubstitution on the aryl portion of the cinnamide results in enhanced activity over mono substitution on the ring. The best 2,3-substituents were chlorine and trifluoromethyl groups. Compounds 39 and 40 which contain two CF3 groups have IC50 values of 0.5 and 0.1 nM, respectively, in inhibiting JY8 cells expressing LFA-1 on their surface, from adhering to ICAM-1. The structure-activity relationship (SAR) was examined using an NMR based model of the LFA-1 I domain/compound 31 complex. One of our compounds (38) was able to reduce cell migration in two different in vivo experiments.

  DOI：

  10.1021/jm0103108
• 作为产物：
  描述：

  3-氯磺酰基-4-氟苯甲酸 、 二甲胺 以 四氢呋喃 为溶剂， 反应 0.5h， 以73%的产率得到3-(dimethylsulfamoyl)-4-fluorobenzoic acid
  参考文献：
  名称：

  用于治疗唐氏综合症核心症状的选择性 NKCC1 抑制剂的设计、合成、体外和体内表征

  摘要：

  细胞内氯化物浓度 [Cl – ] i在几种神经系统疾病中存在缺陷。在神经元中，[Cl – ] i主要受 Na + –K + –Cl –输入端 NKCC1 和 K + –Cl –输出端 KCC2的作用调节。最近，我们报道了发现ARN23746作为一类新型 NKCC1 选择性抑制剂的主要候选物。重要的是，ARN23746能够在小鼠模型中挽救唐氏综合症 (DS) 和自闭症的核心症状。在这里，我们描述了这类化学选择性 NKCC1 抑制剂的发现和广泛表征，重点是ARN23746和其他有前途的衍生物。特别是，我们提出了化合物40 ( ARN24092 ) 作为在 DS 小鼠模型中具有体内功效的备用/后续先导。这些结果进一步加强了这类新化合物在治疗以 NKCC1/KCC2 表达比率缺陷为特征的脑部疾病的核心症状方面的潜力。

  DOI：

  10.1021/acs.jmedchem.1c00603

文献信息

• [EN] MODULATORS OF INTRACELLULAR CHLORIDE CONCENTRATION<br/>[FR] MODULATEURS DE LA CONCENTRATION DE CHLORURE INTRACELLULAIRE
  申请人：FONDAZIONE ST ITALIANO TECNOLOGIA

  公开号：WO2020202072A1

  公开（公告）日：2020-10-08

  The present invention relates to a compound of Formula la, lb and Ic, (Formula Ia) a pharmaceutical composition comprising the same and their use in the treatment or prevention of pathological conditions associated to depolarizing GABAergic transmission including, for example, Down syndrome and autism.

  本发明涉及化合物Ia、Ib和Ic的公式（公式Ia），包括相同的药物组合物以及它们在治疗或预防与去极化GABA能传导相关的病理条件中的用途，例如唐氏综合征和自闭症。
• Sulfamylbenzoic acids
  申请人：Pfizer Inc.

  公开号：US03992441A1

  公开（公告）日：1976-11-16

  Certain mono- and disubstituted-5-sulfamylbenzoic acids, many of which are novel, and their use in lowering blood lipid levels in mammals.

  某些单取代和双取代的5-磺酰基苯甲酸，其中许多是新颖的，并且它们的用途是降低哺乳动物的血脂水平。
• Sulfamylbenzoic acid
  申请人：Pfizer Inc.

  公开号：US04138399A1

  公开（公告）日：1979-02-06

  Certain mono- and disubstituted-5-sulfamylbenzoic acids, many of which are novel, and their use in lowering blood lipid levels in mammals.

  某些单取代和双取代的5-磺酰基苯甲酸，其中许多是新颖的，以及它们在降低哺乳动物血脂水平方面的应用。
• Discovery of a Small Molecule Drug Candidate for Selective NKCC1 Inhibition in Brain Disorders
  作者：Annalisa Savardi、Marco Borgogno、Roberto Narducci、Giuseppina La Sala、Jose Antonio Ortega、Maria Summa、Andrea Armirotti、Rosalia Bertorelli、Andrea Contestabile、Marco De Vivo、Laura Cancedda

  DOI：10.1016/j.chempr.2020.06.017

  日期：2020.8

  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.
• MODULATORS OF INTRACELLULAR CHLORIDE CONCENTRATION
  申请人：Fondazione Istituto Italiano di Tecnologia

  公开号：EP3947345A1

  公开（公告）日：2022-02-09