N-methyl-N-((5-((6-phenyl-1,3-benzothiazol-2-yl)carbonyl)-1,3,4-oxadiazol-2-yl)methyl)sulfamide | 1579303-77-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: N-methyl-N-((5-((6-phenyl-1,3-benzothiazol-2-yl)carbonyl)-1,3,4-oxadiazol-2-yl)methyl)sulfamide
• 英文别名: 2-[[Methyl(sulfamoyl)amino]methyl]-5-(6-phenyl-1,3-benzothiazole-2-carbonyl)-1,3,4-oxadiazole；2-[[methyl(sulfamoyl)amino]methyl]-5-(6-phenyl-1,3-benzothiazole-2-carbonyl)-1,3,4-oxadiazole
• CAS: 1579303-77-7
• 化学式: C₁₈H₁₅N₅O₄S₂
• 分子量: 429.48
• InChiKey: WGSUNDWKFJGNLI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  169
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-(6-phenylbenzo[d]thiazol-2-yl)acetohydrazide 在 双氧水 、 磺酰胺 、 1-丙基磷酸酐 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 溶剂黄146 、 乙酸乙酯 为溶剂， 反应 28.0h， 生成 N-methyl-N-((5-((6-phenyl-1,3-benzothiazol-2-yl)carbonyl)-1,3,4-oxadiazol-2-yl)methyl)sulfamide
  参考文献：
  名称：

  Identification of Reversible Small Molecule Inhibitors of Endothelial Lipase (EL) That Demonstrate HDL-C Increase In Vivo

  摘要：

  Endothelial lipase (EL) hydrolyzes phospholipids in high-density lipoprotein (HDL) resulting in reduction in plasma HDL levels. Studies with murine transgenic, KO, or loss-of-function variants strongly suggest that inhibition of EL will lead to sustained plasma high-density lipoprotein cholesterol (HDL-C) increase and, potentially, a reduced cardiovascular disease (CVD) risk. Herein, we describe the discovery of a series of oxadiazole ketones, which upon optimization, led to the identification of compound 12. Compound 12 was evaluated in a mouse pharmacodynamics (PD) model and demonstrated a 56% increase in plasma HDL-C. In a mouse reverse cholesterol transport study, compound 12 stimulated cholesterol efflux by 53% demonstrating HDL-C functionality.

  DOI：

  10.1021/acs.jmedchem.9b01831

文献信息

• KETONE LINKED BENZOTHIAZOLE INHIBITORS OF ENDOTHELIAL LIPASE
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20150239879A1

  公开（公告）日：2015-08-27

  The present invention provides compounds of Formula (I): as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used as medicament.

  本发明提供了式(I)所定义的化合物以及包含任何这样的新化合物的组合物。这些化合物是内皮酯酶抑制剂，可以用作药物。
• US9169240B2
  申请人：——

  公开号：US9169240B2

  公开（公告）日：2015-10-27
• Identification of Reversible Small Molecule Inhibitors of Endothelial Lipase (EL) That Demonstrate HDL-C Increase In Vivo
  作者：George Tora、Soong-Hoon Kim、Zulan Pi、James A. Johnson、Ji Jiang、Monique Phillips、John Lloyd、Lynn M. Abell、Hao Lu、Gregory Locke、Leonard P. Adam、David S. Taylor、Xiaohong Yin、Kamelia Behnia、Lei Zhao、Richard Yang、Michael Basso、Christian Caporuscio、Alice Ye Chen、Eddie Liu、Todd Kirshgessner、Joelle M. Onorato、Carol Ryan、Sarah C. Traeger、David Gordon、Ruth R. Wexler、Heather J. Finlay

  DOI：10.1021/acs.jmedchem.9b01831

  日期：2020.2.27

  Endothelial lipase (EL) hydrolyzes phospholipids in high-density lipoprotein (HDL) resulting in reduction in plasma HDL levels. Studies with murine transgenic, KO, or loss-of-function variants strongly suggest that inhibition of EL will lead to sustained plasma high-density lipoprotein cholesterol (HDL-C) increase and, potentially, a reduced cardiovascular disease (CVD) risk. Herein, we describe the discovery of a series of oxadiazole ketones, which upon optimization, led to the identification of compound 12. Compound 12 was evaluated in a mouse pharmacodynamics (PD) model and demonstrated a 56% increase in plasma HDL-C. In a mouse reverse cholesterol transport study, compound 12 stimulated cholesterol efflux by 53% demonstrating HDL-C functionality.