methyl 4-((4-((2,4-dioxothiazolidin-5-ylidene)methyl)-phenoxy)methyl)cyclohexanecarboxylate | 1221413-80-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: methyl 4-((4-((2,4-dioxothiazolidin-5-ylidene)methyl)-phenoxy)methyl)cyclohexanecarboxylate
• 英文别名: methyl-4-((4-((2,4-dioxothiazolidine-5-ylidene)methyl)phenoxy)methyl)cyclohexane carboxylate；Methyl-4-((4-((2,4-dioxothiazolidine-5-ylidene)methyl)phenoxy)methyl)cyclohexane carboxylate；methyl 4-[[4-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]phenoxy]methyl]cyclohexane-1-carboxylate
• CAS: 1221413-80-4
• 化学式: C₁₉H₂₁NO₅S
• 分子量: 375.445
• InChiKey: PSYKMFLSDVUOFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 4-((4-((2,4-dioxothiazolidin-5-ylidene)methyl)-phenoxy)methyl)cyclohexanecarboxylate 在 水 、 potassium hydroxide 、 盐酸 作用下， 以 水 为溶剂， 反应 1.0h， 以77.1%的产率得到4-([4-[(Z)-(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]phenoxy]methyl)cyclohexane carboxylic acid
  参考文献：
  名称：

  NOVEL THIAZOLIDINEDIONE DERIVATIVE AND USE THEREOF

  摘要：

  本发明涉及由以下式（I）表示的新型噻唑烷二酮衍生物及其用途。更具体地说，本发明涉及由以下式（I）表示的新型噻唑烷二酮衍生物以及包含其的药物组合物。根据本发明的式（I）的新型噻唑烷二酮衍生物可以通过抑制分解前列腺素的15-羟基前列腺素脱氢酶（15-PGDH）的活性，有效用于预防或治疗心血管疾病、胃肠道疾病和肾脏疾病，同时也用于预防脱发和促进头发生长，以及促进骨生成和伤口愈合。

  公开号：

  US20110269954A1
• 作为产物：
  描述：

  2,4-噻唑烷二酮 、 在 哌啶 、 溶剂黄146 作用下， 以 甲苯 为溶剂， 反应 12.0h， 以74.1%的产率得到methyl 4-((4-((2,4-dioxothiazolidin-5-ylidene)methyl)-phenoxy)methyl)cyclohexanecarboxylate
  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

• Thiazolidinedione derivative and use thereof
  申请人：Cho Hoon

  公开号：US08637558B2

  公开（公告）日：2014-01-28

  The present invention relates to novel thiazolidinedione derivatives expressed by the following formula (I) and the uses thereof. More specifically, the present invention relates to novel thiazolidinedione derivatives expressed by the following formula (I) and a pharmaceutical composition comprising the same. The novel thiazolidinedione derivatives of formula (I) according to the present invention can be effectively used for the prevention or treatment of cardiovascular disease, gastrointestinal disease and renal disease by inhibiting the activity of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) that decomposes prostaglandins as well as useful for the prevention of hair loss and the stimulation of hair growth, and osteogenic stimulation and wound healing.

  本发明涉及以下式(I)所表示的新型噻唑烷二酮衍生物及其用途。更具体地说，本发明涉及以下式(I)所表示的新型噻唑烷二酮衍生物及其制备的药物组合物。根据本发明的新型噻唑烷二酮衍生物可以有效用于抑制降解前列腺素的15-羟基前列腺素脱氢酶（15-PGDH）的活性，从而预防或治疗心血管疾病、胃肠道疾病和肾脏疾病，并且有助于预防脱发和促进头发生长，以及促进骨生成和伤口愈合。
• 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.
• NOVEL THIAZOLIDINEDIONE DERIVATIVE AND USE THEREOF
  申请人：Cho Hoon

  公开号：US20110269954A1

  公开（公告）日：2011-11-03

  The present invention relates to novel thiazolidinedione derivatives expressed by the following formula (I) and the uses thereof. More specifically, the present invention relates to novel thiazolidinedione derivatives expressed by the following formula (I) and a pharmaceutical composition comprising the same. The novel thiazolidinedione derivatives of formula (I) according to the present invention can be effectively used for the prevention or treatment of cardiovascular disease, gastrointestinal disease and renal disease by inhibiting the activity of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) that decomposes prostaglandins as well as useful for the prevention of hair loss and the stimulation of hair growth, and osteogenic stimulation and wound healing.

  本发明涉及由以下式（I）表示的新型噻唑烷二酮衍生物及其用途。更具体地说，本发明涉及由以下式（I）表示的新型噻唑烷二酮衍生物以及包含其的药物组合物。根据本发明的式（I）的新型噻唑烷二酮衍生物可以通过抑制分解前列腺素的15-羟基前列腺素脱氢酶（15-PGDH）的活性，有效用于预防或治疗心血管疾病、胃肠道疾病和肾脏疾病，同时也用于预防脱发和促进头发生长，以及促进骨生成和伤口愈合。