1,1-二甲基乙基-N-[((4-氯苯基)甲基]-N-[(5-硝基-2-噻吩基)甲基])甘氨酸盐 | 1216744-19-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 1,1-二甲基乙基-N-[((4-氯苯基)甲基]-N-[(5-硝基-2-噻吩基)甲基])甘氨酸盐
• 英文名称: GSK 4112
• 英文别名: (1,1-dimethylethyl N-[(4-chlorophenyl)methyl]-N-[(5-nitro-2-thienyl)methyl])glycinate；1,1-dimethylethyl N-[(4-chlorophenyl)methyl]-N-[(5-nitro-2-thienyl)methyl]glycinate；GSK4112；SR6452；SGN；Tert-butyl 2-[(4-chlorophenyl)methyl-[(5-nitrothiophen-2-yl)methyl]amino]acetate
• CAS: 1216744-19-2
• 化学式: C₁₈H₂₁ClN₂O₄S
• 分子量: 396.895
• InChiKey: WYSLOKHVFKLWOU-UHFFFAOYSA-N

物化性质

• 熔点：
  95 - 96°C
• 沸点：
  486.7±45.0 °C(Predicted)
• 密度：
  1.296±0.06 g/cm3(Predicted)
• 溶解度：
  氯仿（微溶）、甲醇（微溶、加热）

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  104
• 氢给体数：
  0
• 氢受体数：
  6

安全信息

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

制备方法与用途

生物活性方面，GSK4112是一种Rev-erbα激动剂，其EC50值为0.4 μM。GSK4112是用于研究核受体REV-erbα细胞生物学的小分子化学探针。

反应信息

• 作为产物：
  描述：

  5-硝基噻吩-2-甲醛 、 tert-butyl N-[(4-chlorophenyl)methyl]glycinate 在 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 生成 1,1-二甲基乙基-N-[((4-氯苯基)甲基]-N-[(5-硝基-2-噻吩基)甲基])甘氨酸盐
  参考文献：
  名称：

  Optimized Chemical Probes for REV-ERBα

  摘要：

  REV-ERB alpha has emerged as an important target for regulation of circadian rhythm and its associated physiology. Herein, we report on the optimization of a series of REV-ERB alpha agonists based on G5K4112 (1) for potency, selectivity, and bioavailability.(1) Potent REV-ERB alpha agonists 4, 10, 16, and 23 are detailed for their ability to suppress BMAL and IL-6 expression from human cells while also demonstrating excellent selectivity over LAR alpha. Amine 4 demonstrated in vivo bioavailability after either iv or oral dosing.

  DOI：

  10.1021/jm400458q

文献信息

• Methods of Treating Portal Hypertension
  申请人：THE CHARLOTTE-MECKLENBURG HOSPITAL AUTHORITY D/B/A CAROLINAS HEALTHCARE SYSTEM

  公开号：US20150313871A1

  公开（公告）日：2015-11-05

  The present invention provides methods for treating or preventing portal hypertension comprising administering to a patient in need of such treatment or prevention at least one Rev-erb modulating agent (REMA) in an amount effective to treat or prevent said portal hypertension. The REMA can be SR6452 or a related compound, such as SR9009 or SR9011. The amount of the REMA administered can comprises a quantity sufficient to modulate Rev-erbα expression, activity, and/or subcellular location and/or to inhibit or reverse hepatic stellate cell (HSC) activation and contractility.
• Methods of Treating Hepatic Fibrosis and Associated Diseases by Regulating Rev-ERB Activity
  申请人：The Charlotte-Mecklenburg Hospital Authority d/b/a Carolinas Healthcare System

  公开号：US20150328186A1

  公开（公告）日：2015-11-19

  The present invention is directed to compositions and associated methods for treatment, prevention, amelioration, and/or delaying the onset of hepatic fibrosis and/or associated diseases. The methods preferably involve regulating at least one of Rev-erbα expression, activity, and subcellular localization. In particular, certain embodiments of the present invention relate to compositions and methods of using a Rev-erb-modulating agent (REMA) for the treatment or prevention of hepatic fibrosis and/or associated diseases. Preferably, the amount of a REMA administered comprises a quantity sufficient to modulate at least one of Rev-erbα expression, activity, and subcellular localization and reduce the activation of hepatic stellate cells (HSCs).
• US9750718B2
  申请人：——

  公开号：US9750718B2

  公开（公告）日：2017-09-05
• US9872851B2
  申请人：——

  公开号：US9872851B2

  公开（公告）日：2018-01-23
• [EN] TREATING INFLAMMATORY DISEASES BY ADMINISTRATION OF REV-ERB a LIGANDS<br/>[FR] TRAITEMENT DE MALADIES INFLAMMATOIRES PAR ADMINISTRATION DE LIGANDS DE REV-ERB ?
  申请人：GLAXO GROUP LTD

  公开号：WO2011022619A1

  公开（公告）日：2011-02-24

  The invention relates to methods of modulating inflammatory diseases by administration of REV-ERB α nuclear receptor ligands, and to REV-ERB α ligands compounds.