5-(4-((2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methoxy)benzylidene)thiazolidine-2,4-dione | 148833-66-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: 5-(4-((2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methoxy)benzylidene)thiazolidine-2,4-dione
• 英文别名: 5-(4-((2,3-Dihydrobenzo[b][1,4]dioxin-2-yl)methoxy)benzylidene)thiazolidine-2,4-dione；5-[[4-(2,3-dihydro-1,4-benzodioxin-3-ylmethoxy)phenyl]methylidene]-1,3-thiazolidine-2,4-dione
• CAS: 148833-66-3
• 化学式: C₁₉H₁₅NO₅S
• 分子量: 369.398
• InChiKey: DFEJSZCZXHPODS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  99.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2,4-噻唑烷二酮 、 2-((4-formylphenoxy)methyl)-2,3-dihydrobenzo[1,4]dioxine 在 哌啶 、 溶剂黄146 作用下， 以 甲苯 为溶剂， 反应 12.0h， 以82.4%的产率得到5-(4-((2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methoxy)benzylidene)thiazolidine-2,4-dione
  参考文献：
  名称：

  Synthesis and SAR of thiazolidinedione derivatives as 15-PGDH inhibitors

  摘要：

  Prostaglandins have a short life in vivo because they are metabolized rapidly by oxidation to 15-ketoprostaglandins catalyzed by a cytosolic enzyme known as NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Previously, CT-8, a thiazolidinedione analogue, was found to be a potent inhibitor of 15-PGDH. Structure-activity analysis indicated that the N-methylation of thiazolidine-2,4-dione, CT-8, abolished the inhibitory activity, whereas the introduction of an ethyl hydroxyl group at amine in CT-8 still had a good inhibitory effect. Based on the structures of the thiazolidinediones analogues and inhibitory activity, a range of benzylidene thiazolidinedione derivatives were synthesized with different substituents on the phenyl ring and their inhibitory activity was evaluated. Replacement of the cyclohexylethyl group of CT-8 with the hetero five-member ring increased the inhibitory potency. However, replacement of the cyclohexylethyl group with a hetero six-member ring decreased the inhibitory potency significantly. It was found that compound 2 (5-(4-(2-(thiophen-2yl) ethoxy) benzylidene) thiazolidine-2,4-dione) was the most potent inhibitor that was effective in the nanomolar range. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.01.016

文献信息

• Synthesis and SAR of thiazolidinedione derivatives as 15-PGDH inhibitors
  作者：Ying Wu、Hsin-Hsiung Tai、Hoon Cho

  DOI：10.1016/j.bmc.2010.01.016

  日期：2010.2

  Prostaglandins have a short life in vivo because they are metabolized rapidly by oxidation to 15-ketoprostaglandins catalyzed by a cytosolic enzyme known as NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Previously, CT-8, a thiazolidinedione analogue, was found to be a potent inhibitor of 15-PGDH. Structure-activity analysis indicated that the N-methylation of thiazolidine-2,4-dione, CT-8, abolished the inhibitory activity, whereas the introduction of an ethyl hydroxyl group at amine in CT-8 still had a good inhibitory effect. Based on the structures of the thiazolidinediones analogues and inhibitory activity, a range of benzylidene thiazolidinedione derivatives were synthesized with different substituents on the phenyl ring and their inhibitory activity was evaluated. Replacement of the cyclohexylethyl group of CT-8 with the hetero five-member ring increased the inhibitory potency. However, replacement of the cyclohexylethyl group with a hetero six-member ring decreased the inhibitory potency significantly. It was found that compound 2 (5-(4-(2-(thiophen-2yl) ethoxy) benzylidene) thiazolidine-2,4-dione) was the most potent inhibitor that was effective in the nanomolar range. (C) 2010 Elsevier Ltd. All rights reserved.