8-ethyl-5-oxo-2-(4-((4-(trifluoromethyl)phenyl)carbamothioyl)piperazin-1-yl)-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid | 1206482-87-2

• 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: 8-ethyl-5-oxo-2-(4-((4-(trifluoromethyl)phenyl)carbamothioyl)piperazin-1-yl)-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
• 英文别名: 2-(4-{[(4-trifluoromethylphenyl)amino]carbonothioyl}-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid；8-ethyl-5-oxo-2-[4-[[4-(trifluoromethyl)phenyl]carbamothioyl]piperazin-1-yl]pyrido[2,3-d]pyrimidine-6-carboxylic acid
• CAS: 1206482-87-2
• 化学式: C₂₂H₂₁F₃N₆O₃S
• 分子量: 506.508
• InChiKey: DEKWQMMVPGEFFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  35
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  134
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  4-(三氟甲基)异硫氰酸苯酯 、 吡哌酸 在 silica 作用下， 生成 8-ethyl-5-oxo-2-(4-((4-(trifluoromethyl)phenyl)carbamothioyl)piperazin-1-yl)-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
  参考文献：
  名称：

  Pipemidic acid derivative autotaxin inhibitors

  摘要：

  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。

  公开号：

  US08497371B2

文献信息

• [EN] PIPEMIDIC ACID DERIVATIVE AUTOTAXIN INHIBITORS<br/>[FR] INHIBITEURS D'AUTOTAXINE DÉRIVÉS D'ACIDE PIPÉMIDIQUE
  申请人：UNIV MEMPHIS RES FOUNDATION

  公开号：WO2011053597A1

  公开（公告）日：2011-05-05

  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.

  提供了一类新颖和优化的pipemidic酸衍生物化合物，这些化合物表现出对自体脂肪酶酶的有效抑制。这类化合物表现出与自体脂肪酶的反应性，最终减小其上的反应性位点的大小，以防止将溶酶磷脂酰胆碱转化为溶酶磷脂酸。此外，这类化合物可以被纳入人体摄入的输送形式中。因此，这些化合物提供了一种优秀的潜在方式，可以减少由于人体内天然存在的自体脂肪酶而导致的某些癌症的生成。在该发明中还包括了使用这些化合物使自体脂肪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：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型和优化的pipemidic酸衍生物类化合物，它们能够有效地抑制自体趋化素酶。这些化合物类别表现出与自体趋化素反应性，最终减小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体摄入的递送形式中。因此，这些化合物为潜在地减少由于人体内天然存在的自体趋化素而导致某些癌症的产生提供了出色的方式。本发明还涵盖了使用这些化合物使自体趋化素在一定程度上失活的方法。
• Identification of a potent small-molecule inhibitor of bacterial DNA repair that potentiates quinolone antibiotic activity in methicillin-resistant Staphylococcus aureus
  作者：Carine S.Q. Lim、Kam Pou Ha、Rebecca S. Clarke、Leigh-Anne Gavin、Declan T. Cook、Jennie A. Hutton、Charlotte L. Sutherell、Andrew M. Edwards、Lindsay E. Evans、Edward W. Tate、Thomas Lanyon-Hogg

  DOI：10.1016/j.bmc.2019.06.025

  日期：2019.10

  The global emergence of antibiotic resistance is one of the most serious challenges facing modern medicine. There is an urgent need for validation of new drug targets and the development of small molecules with novel mechanisms of action. We therefore sought to inhibit bacterial DNA repair mediated by the AddAB/RecBCD protein complexes as a means to sensitize bacteria to DNA damage caused by the host immune system or quinolone antibiotics. A rational, hypothesis-driven compound optimization identified IMP-1700 as a cell-active, nanomolar potency compound. IMP-1700 sensitized multidrug-resistant Staphylococcus aureus to the fluoroquinolone antibiotic ciprofloxacin, where resistance results from a point mutation in the fluoroquinolone target, DNA gyrase. Cellular reporter assays indicated IMP-1700 inhibited the bacterial SOS-response to DNA damage, and compoundfunctionalized Sepharose successfully pulled-down the AddAB repair complex. This work provides validation of bacterial DNA repair as a novel therapeutic target and delivers IMP-1700 as a tool molecule and starting point for therapeutic development to address the pressing challenge of antibiotic resistance.
• ANTIBIOTIC COMPOUNDS AND COMPOSITIONS, AND METHODS FOR IDENTIFICATION THEREOF
  申请人：Fred Hutchinson Cancer Research Center

  公开号：US20170305899A1

  公开（公告）日：2017-10-26

  Disclosed herein are compounds and methods for inhibiting bacterial DNA repair enzymes, including AddAB and RecBCD helicase-nucleases. Pharmaceutical compositions and methods for treating a subject with an antibacterial agent are also disclosed herein.
• US8497371B2
  申请人：——

  公开号：US8497371B2

  公开（公告）日：2013-07-30