Ethyl 8-methoxy-4-(piperazin-1-yl)quinoline-3-carboxylate

• 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: Ethyl 8-methoxy-4-(piperazin-1-yl)quinoline-3-carboxylate
• 英文别名: ethyl 8-methoxy-4-piperazin-1-ylquinoline-3-carboxylate
• 化学式: C₁₇H₂₁N₃O₃
• mdl: MFCD06617804
• 分子量: 315.372
• InChiKey: OLWRDQRYQVXBAR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  63.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-溴氯苯 、 Ethyl 8-methoxy-4-(piperazin-1-yl)quinoline-3-carboxylate 在 tris-(dibenzylideneacetone)dipalladium(0) 、 三叔丁基膦 、 sodium t-butanolate 作用下， 以 甲苯 为溶剂， 反应 1.0h， 生成 Ethyl 4-[4-(2-chlorophenyl)piperazin-1-yl]-8-methoxyquinoline-3-carboxylate
  参考文献：
  名称：

  Synthesis and SAR of a series of mGlu7 NAMs based on an ethyl-8-methoxy-4-(4-phenylpiperazin-1-yl)quinoline carboxylate core

  摘要：

  A High-Throughput Screening (HTS) campaign identified a fundamentally new mGlu₇ NAM chemotype, based on an ethyl-8-methoxy-4-(4-phenylpiperazin-1-yl)quinolone carboxylate core. The initial hit, VU0226390, was a potent mGlu₇ NAM (IC₅₀ = 647 nM, 6% L-AP4 min) with selectivity versus the other group III mGlu receptors (>30 μM vs. mGlu₄ and mGlu₈). A multi-dimensional optimization effort surveyed all regions of this new chemotype, and found very steep SAR, reminiscent of allosteric modulators, and unexpected piperazine mimetics (whereas classical bioisosteres failed). While mGlu₇ NAM potency could be improved (IC₅₀s ~ 350 nM), the necessity of the ethyl ester moiety and poor physiochemical and DMPK properties precluded optimization towards in vivo tool compounds or clinical candidates. Still, this hit-to-lead campaign afforded key medicinal chemistry insights and new opportunities.

  DOI：

  10.1016/j.bmcl.2020.127529
• 作为产物：
  描述：

  4-氯-8-甲氧基喹啉-3-甲酸乙酯 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 Ethyl 8-methoxy-4-(piperazin-1-yl)quinoline-3-carboxylate
  参考文献：
  名称：

  Synthesis and SAR of a series of mGlu7 NAMs based on an ethyl-8-methoxy-4-(4-phenylpiperazin-1-yl)quinoline carboxylate core

  摘要：

  A High-Throughput Screening (HTS) campaign identified a fundamentally new mGlu₇ NAM chemotype, based on an ethyl-8-methoxy-4-(4-phenylpiperazin-1-yl)quinolone carboxylate core. The initial hit, VU0226390, was a potent mGlu₇ NAM (IC₅₀ = 647 nM, 6% L-AP4 min) with selectivity versus the other group III mGlu receptors (>30 μM vs. mGlu₄ and mGlu₈). A multi-dimensional optimization effort surveyed all regions of this new chemotype, and found very steep SAR, reminiscent of allosteric modulators, and unexpected piperazine mimetics (whereas classical bioisosteres failed). While mGlu₇ NAM potency could be improved (IC₅₀s ~ 350 nM), the necessity of the ethyl ester moiety and poor physiochemical and DMPK properties precluded optimization towards in vivo tool compounds or clinical candidates. Still, this hit-to-lead campaign afforded key medicinal chemistry insights and new opportunities.

  DOI：

  10.1016/j.bmcl.2020.127529

文献信息

• New quinoline-thiolactone conjugates as potential antitubercular and antibacterial agents
  作者：Shaikh Faazil、M. Shaheer Malik、Saleh A. Ahmed、Qazi Mohammad Sajid Jamal、Shaikh Thoukhir Basha、Munirah M. Al-Rooqi、Rami J. Obaid、Jihan Qurban、Iqbal N Shaikh、Basim H. Asghar、Ahmed Kamal

  DOI：10.1016/j.molstruc.2022.134099

  日期：2023.1

  elevated infection rates and drug resistance. New chemical agents need to be developed to address them. Thiolactomycin and quinolines are promising lead molecules in the design of new antitubercular and antibacterial agents. Herein, we report the design and synthesis of series of new quinoline-thiolactone conjugates as potential antitubercular and antibacterial agents. Two of the conjugates, 6b and 6d, exhibited

  由于感染率和耐药性升高，结核病和细菌感染是主要挑战。需要开发新的化学试剂来解决这些问题。硫乳霉素和喹啉是新型抗结核和抗菌药物设计中很有前途的先导分子。在此，我们报告了一系列新型喹啉-硫内酯偶联物作为潜在的抗结核和抗菌剂的设计和合成。其中两种偶联物6b和6d表现出良好的抗结核活性，MIC 值为 8 µg/mL。对接研究表明，缀合物6b和6d对结核分枝杆菌的靶蛋白 KasA 表现出良好的结合亲和力. 另外两种结合物也显示出良好的抗菌活性，MIC 值为 8 µg/mL。此外，缀合物7a的对接优于标准药物利奈唑胺对三种不同分子受体的对接。
• Synthesis and SAR of a series of mGlu7 NAMs based on an ethyl-8-methoxy-4-(4-phenylpiperazin-1-yl)quinoline carboxylate core
  作者：Jacob J. Kalbfleisch、Carson W. Reed、Charlotte Park、Paul K. Spearing、Marc C. Quitalig、Matthew T. Jenkins、Alice L. Rodriguez、Anna L. Blobaum、P. Jeffrey Conn、Colleen M. Niswender、Craig W. Lindsley

  DOI：10.1016/j.bmcl.2020.127529

  日期：2020.11

  A High-Throughput Screening (HTS) campaign identified a fundamentally new mGlu₇ NAM chemotype, based on an ethyl-8-methoxy-4-(4-phenylpiperazin-1-yl)quinolone carboxylate core. The initial hit, VU0226390, was a potent mGlu₇ NAM (IC₅₀ = 647 nM, 6% L-AP4 min) with selectivity versus the other group III mGlu receptors (>30 μM vs. mGlu₄ and mGlu₈). A multi-dimensional optimization effort surveyed all regions of this new chemotype, and found very steep SAR, reminiscent of allosteric modulators, and unexpected piperazine mimetics (whereas classical bioisosteres failed). While mGlu₇ NAM potency could be improved (IC₅₀s ~ 350 nM), the necessity of the ethyl ester moiety and poor physiochemical and DMPK properties precluded optimization towards in vivo tool compounds or clinical candidates. Still, this hit-to-lead campaign afforded key medicinal chemistry insights and new opportunities.