3-(2-氯苯基)-n-(4-氯苯基)-n,5-二甲基-4-异噁唑羧酰胺 | 1197300-24-5

• 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: 3-(2-氯苯基)-n-(4-氯苯基)-n,5-二甲基-4-异噁唑羧酰胺
• 中文别名: 3-(2-氯苯基)-N-(4-氯苯基)-N,5-二甲基异恶唑-4-甲酰胺；TGR5抑制剂；TGR5受体激动剂；3-（2-氯苯基）-N-（4-氯苯基）-N，5-二甲基-4-异恶唑甲酰胺；化合物TGR5；3-(2-氯苯基)-N-(4-氯苯基)-N,5-二甲基-4-异噁唑羧酰胺；TGR5G蛋白受体激动剂；3-(2-氯苯基)-N-(4-氯苯基)-N,5-二甲基-4-异恶唑甲酰胺
• 英文名称: 3‐(2‐chlorophenyl)‐N‐(4‐chlorophenyl)‐N,5‐dimethylisoxazole‐4‐carboxamide
• 英文别名: 3-(2-chlorophenyl)-N-(4-chlorophenyl)-N,5-dimethyl-4-isoxazolecarboxamide；3-(2-chlorophenyl)-N-(4-chlorophenyl)-N,5-dimethylisoxazole-4-carboxamide；GPBARA；TGR5 Receptor Agonist；3-(2-chlorophenyl)-N-(4-chlorophenyl)-N,5-dimethyl-1,2-oxazole-4-carboxamide
• CAS: 1197300-24-5
• 化学式: C₁₈H₁₄Cl₂N₂O₂
• 分子量: 361.227
• InChiKey: IGRCWJPBLWGNPX-UHFFFAOYSA-N

物化性质

• 沸点：
  541.8±50.0 °C(Predicted)
• 密度：
  1.346±0.06 g/cm3(Predicted)
• 溶解度：
  DMF：50 mg/ml； DMSO：50 mg/ml； DMSO:PBS (pH 7.2) (1:4)：0.2 mg/ml；乙醇：30 mg/ml

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  46.3
• 氢给体数：
  0
• 氢受体数：
  3

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,H320,H335
• 储存条件：
  -20℃

制备方法与用途

生物活性

TGR5 Receptor Agonist (CCDC) 是 TGR5（GPCR19）的激动剂。

靶点

• IC50 值：6.8（pEC₅₀，U2-OS 细胞测定）；7.5（pEC₅₀，色素细胞）

反应信息

• 作为产物：
  描述：

  4-氯-N-甲基苯胺 、 3-(2-氯苯基)-5-甲基-4-异恶唑甲酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以74%的产率得到3-(2-氯苯基)-n-(4-氯苯基)-n,5-二甲基-4-异噁唑羧酰胺
  参考文献：
  名称：

  Discovery of 3-Aryl-4-isoxazolecarboxamides as TGR5 Receptor Agonists

  摘要：

  A series of 3-aryl-4-isoxazolecarboxamides identified from a high-throughput screening campaign as novel, potent small molecule agonists of the human TGR5 G-protein coupled receptor is described. Subsequent optimization resulted in the rapid identification of potent exemplars 6 and 7 which demonstrated improved GLP-1 secretion in vivo via an intracolonic dose coadministered with glucose challenge in a canine model. These novel TGR5 receptor agonists are potentially useful therapeutics for metabolic disorders such as type II diabetes and its associated complications.

  DOI：

  10.1021/jm901434t

文献信息

• THERAPEUTIC COMPOUNDS THAT SUPPRESS PROTEIN ARGININE METHYLTRANSFERASE ACTIVITY FOR REDUCING TUMOR CELL PROLIFERATION
  申请人：Epinova Therapeutics Corp.

  公开号：US20160271149A1

  公开（公告）日：2016-09-22

  The described invention provides methods for modulating gene expression of a gene related to proliferation of a population of tumor cells. The method entails administering a therapeutic amount of a therapeutic compound to a cell, a tissue, or a mammal, wherein the therapeutic amount of the therapeutic compound is effective to suppress methyltransferase activity of a protein arginine methyltransferase. Modulation of the protein arginine methyltransferase activity in turn modulates methylation of a target protein that affects gene expression of the gene, and may suppress the proliferation of the population of tumor cells.
• COMPOSITIONS AND METHODS FOR THE TREATMENT OF LIVER DISORDERS
  申请人：Viking Therapeutics, Inc.

  公开号：US20220016136A1

  公开（公告）日：2022-01-20

  The present disclosure is directed toward the use of thyroid receptor agonists of pharmaceutically acceptable salts thereof, in combination with a second pharmaceutical agent for preventing, treating, or ameliorating fatty liver diseases such as steatosis, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis.
• [EN] THERAPEUTIC COMPOUNDS THAT SUPPRESS PROTEIN ARGININE METHYLTRANSFERASE ACTIVITY FOR REDUCING TUMOR CELL PROLIFERATION<br/>[FR] COMPOSÉS THÉRAPEUTIQUES QUI SUPPRIMENT L'ACTIVITÉ DE LA PROTÉINE ARGININE MÉTHYLTRANSFÉRASE POUR RÉDUIRE LA PROLIFÉRATION DE CELLULES TUMORALES
  申请人：EPINOVA THERAPEUTICS CORP

  公开号：WO2016149299A1

  公开（公告）日：2016-09-22

  The described invention provides methods for modulating gene expression of a gene related to proliferation of a population of tumor cells. The method entails administering a therapeutic amount of a therapeutic compound to a cell, a tissue, or a mammal, wherein the therapeutic amount of the therapeutic compound is effective to suppress methyltransferase activity of a protein arginine methyltransferase. Modulation of the protein arginine methyltransferase activity in turn modulates methylation of a target protein that affects gene expression of the gene, and may suppress the proliferation of the population of tumor cells.
• Discovery of 3-Aryl-4-isoxazolecarboxamides as TGR5 Receptor Agonists
  作者：Karen A. Evans、Brian W. Budzik、Sean A. Ross、David D. Wisnoski、Jian Jin、Ralph A. Rivero、Mythily Vimal、George R. Szewczyk、Channa Jayawickreme、David L. Moncol、Thomas J. Rimele、Susan L. Armour、Susan P. Weaver、Robert J. Griffin、Sarva M. Tadepalli、Michael R. Jeune、Todd W. Shearer、Zibin B. Chen、Lihong Chen、Donald L. Anderson、J. David Becherer、Maite De Los Frailes、Francisco Javier Colilla

  DOI：10.1021/jm901434t

  日期：2009.12.24

  A series of 3-aryl-4-isoxazolecarboxamides identified from a high-throughput screening campaign as novel, potent small molecule agonists of the human TGR5 G-protein coupled receptor is described. Subsequent optimization resulted in the rapid identification of potent exemplars 6 and 7 which demonstrated improved GLP-1 secretion in vivo via an intracolonic dose coadministered with glucose challenge in a canine model. These novel TGR5 receptor agonists are potentially useful therapeutics for metabolic disorders such as type II diabetes and its associated complications.