2-(4-{[(3-Benzothiadiazolphenyl)amino]carbonothioyl}-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic Acid | 1206482-73-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-(4-{[(3-Benzothiadiazolphenyl)amino]carbonothioyl}-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic Acid
• 英文别名: 2-[4-(2,1,3-benzothiadiazol-5-ylcarbamothioyl)piperazin-1-yl]-8-ethyl-5-oxopyrido[2,3-d]pyrimidine-6-carboxylic acid
• CAS: 1206482-73-6
• 化学式: C₂₁H₂₀N₈O₃S₂
• 分子量: 496.574
• InChiKey: TXKCPYNQAWJPHH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  188
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2,1,3-苯并噻二唑-5-异硫氰酸酯 、 吡哌酸 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以58%的产率得到2-(4-{[(3-Benzothiadiazolphenyl)amino]carbonothioyl}-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic Acid
  参考文献：
  名称：

  Optimization of a Pipemidic Acid Autotaxin Inhibitor

  摘要：

  Autotaxin (ATX, NPP2) has recently been shown to be the lysophospholipase D responsible for synthesis of the bioactive lipid lysophosphatidic acid (LPA). LPA has a well-established role in cancer, and the production of LPA is consistent with the cancer-promoting actions of ATX. Increased ATX and LPA receptor expression have been found in numerous cancer cell types. The current study has combined ligand-based computational approaches (binary quantitative structure-activity relationship), medicinal chemistry, and experimental enzymatic assays to optimize a previously identified small molecule ATX inhibitor, H2L 7905958 (1). Seventy prospective analogs were analyzed via computational screening, from which 30 promising compounds were synthesized and screened to assess efficacy, potency, and mechanism of inhibition. This approach has identified four analogs as potent as or more potent than the lead. The most potent analog displayed an IC50 of 900 nM with respect to ATX-mediated FS-3 hydrolysis with a K-i of 700 nM, making this compound approximately 3-fold more potent than the previously described lead.

  DOI：

  10.1021/jm9012328

文献信息

• PIPEMIDIC ACID DERIVATIVE AUTOTAXIN INHIBITORS
  申请人：Parrill-Baker Abby Louise

  公开号：US20120100592A1

  公开（公告）日：2012-04-26

  Novel and optimized classes of pipemidic acid derivative compounds that exhibit effective inhibition of autotaxin enzymes are provided. Such classes of compounds exhibit exhibit reactivity with autotaxin to ultimately reduce the size of the reactive sites thereon to prevent conversion of lysophosphatidyl choline to lysophophatidic acid. Furthermore, such compounds can be incorporated within delivery forms for human ingestion. As such, these compounds accord an excellent manner of potentially reducing generation of certain cancers attributable to the presence of naturally occurring autotaxin within the human body. Methods of inactivating autotaxin to certain degrees therewith such compounds are encompassed within invention as well.

  本发明提供了一种新颖且优化的pipemidic酸衍生物类，其表现出有效抑制自体移行酶酶的作用。这些化合物类表现出与自体移行酶的反应性，最终减少其上的反应性位点的大小，以防止溶血磷脂酰胆碱转化为溶血磷脂酸。此外，这些化合物可以被纳入人类摄入的递送形式中。因此，这些化合物提供了一种可能减少由于人体内天然存在的自体移行酶而产生某些癌症的优秀方法。本发明还涵盖了使用这些化合物将自体移行酶失活到一定程度的方法。
• Pipemidic acid derivative autotaxin inhibitors
  申请人：Parrill-Baker Abby Louise

  公开号：US08497371B2

  公开（公告）日：2013-07-30

  Novel and optimized classes of pipemidic acid derivative compounds that exhibit effective inhibition of autotaxin enzymes are provided. Such classes of compounds exhibit exhibit reactivity with autotaxin to ultimately reduce the size of the reactive sites thereon to prevent conversion of lysophosphatidyl choline to lysophophatidic acid. Furthermore, such compounds can be incorporated within delivery forms for human ingestion. As such, these compounds accord an excellent manner of potentially reducing generation of certain cancers attributable to the presence of naturally occurring autotaxin within the human body. Methods of inactivating autotaxin to certain degrees therewith such compounds are encompassed within invention as well.

  本发明提供了一种新型优化的吡啶酸衍生物化合物类，这些化合物类表现出有效的抑制自动趋化素酶酶活性。这些化合物类表现出与自动趋化素酶的反应性，最终减小其反应位点的大小，以防止溶血磷脂酰胆碱转化为溶血磷脂酸。此外，这些化合物可以被纳入人体摄入的递送形式中。因此，这些化合物可以可能地减少由于人体内天然存在的自动趋化素酶而导致的某些癌症的发生。本发明还涵盖了使用这些化合物在不同程度上失活自动趋化素酶的方法。