1-(4-chlorophenyl)-3-(4-(pyridin-2-yl)piperazin-1-yl)propan1-one | 861964-86-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-chlorophenyl)-3-(4-(pyridin-2-yl)piperazin-1-yl)propan1-one
• 英文别名: 1-(4-Chlorophenyl)-3-(4-pyridin-2-yl-piperazin-1-yl)propan-1-one；1-(4-chlorophenyl)-3-(4-pyridin-2-ylpiperazin-1-yl)propan-1-one
• CAS: 861964-86-5
• 化学式: C₁₈H₂₀ClN₃O
• 分子量: 329.829
• InChiKey: HCSATKXVYZITCI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  36.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(4-chlorophenyl)-3-(4-(pyridin-2-yl)piperazin-1-yl)propan1-one 在 氢氧化钾 、 碘苯二乙酸 、 硫酸 作用下， 以 氯仿 为溶剂， 反应 37.0h， 生成 (1Z)-1-(4-chlorophenyl)-2-hydroxy-3-(4-pyridin-2-ylpiperazin-1-yl)propan-1-one O-methyloxime
  参考文献：
  名称：

  1-Aryl-3-(4-pyridine-2-ylpiperazin-1-yl)propan-1-one Oximes as Potent Dopamine D₄ Receptor Agonists for the Treatment of Erectile Dysfunction

  摘要：

  A new series of dopamine D-4 receptor agonists, 1-aryl-3-(4-pyridinepiperazin-1-yl) propanone oximes, was designed through the modification of known dopamine D4 receptor agonist PD 168077. Replacement of the amide group with a methylene-oxime moiety produced compounds with improved stability and efficacy. Structure-activity relationsips (SAR) of the aromatic ring linked to the N-4-piperazine ring confirmed the superiority of 2-pyridine as a core for D4 agonist activity. A two-methylene linker between the oxime group and the N-1-piperazine ring displayed the best profile. New dopamine D4 receptor agonists, exemplified by (E)-1-(4-chlorophenyl)-3-(4-pyridin-2-ylpiperazin-1-yl) propan-1-one O-methyloxime (59a) and (E)-1-(3-chloro- 4-fluorophenyl)-3-(4-pyridin-2-ylpiperazin-1-yl) propan-1-one O-methyloxime (64a), exhibited favorable pharmacokinetic profiles and showed oral bioavailability in rat and dog. Subsequent evaluation of 59a in the rat penile erection model revealed in vivo activity, comparable in efficacy to apomorphine. Our results suggest that the oximes provide a novel structural linker for 4-arylpiperazine-based D4 agonists, possessing leadlike quality and with potential to develop a new class of potent and selective dopamine D4 receptor agonists.

  DOI：

  10.1021/jm060279f
• 作为产物：
  描述：

  1-(2-吡啶基)哌嗪 、 3,4'-二氯苯丙酮 在 sodium carbonate 作用下， 以 乙腈 为溶剂， 以67 %的产率得到1-(4-chlorophenyl)-3-(4-(pyridin-2-yl)piperazin-1-yl)propan1-one
  参考文献：
  名称：

  2,3-二酮哌嗪作为开发新的抗 Chagasic 药物的潜在支架

  摘要：

  继续我们开发具有潜在抗克氏锥虫活性的化合物的计划，在这项工作中，我们设计、合成并在体外对锥体鞭毛体进行了评估，形成了一系列新的 2,3-二酮哌嗪衍生物。通过两步序列，其中一步是催化和选择性 C( sp 3 )-H 键反应，获得了九种最终化合物 ( 5a-i )。 与参考药物苯并咪唑 (Bzn) 和硝呋替莫 (Nfx) 相比，这些 2,3-二酮哌嗪中的大多数对锥体鞭毛体菌株 NINOA 具有高活性（LC 50 < 100 μM）。同样，化合物5c和5h显示出对锥体鞭毛体菌株 A1 的高效力（LC50  = 25.2 和 40.49 μM，分别），其中5c的活性是参考药物的四到五倍。此外，这些化合物的细胞毒性是在小鼠巨噬细胞 J774 细胞系中测定的，在大多数情况下，与 Bzn 和 Nfx 相比，它们具有更高的选择性。计算机研究表明，这些 2,3-二酮哌嗪衍生物可能是细胞溶质和线粒体水平的 Fe-SOD

  DOI：

  10.1007/s00044-022-03003-9

文献信息

• Oximes and hydrazones that are useful in treating sexual dysfunction
  申请人：Kolasa Teodzyj

  公开号：US20050176727A1

  公开（公告）日：2005-08-11

  The present invention relates to oximes and hydrazones of formula (I) for the treatment of sexual dysfunction and to compositions containing compounds of formula (I) for the treatment of sexual dysfunction.

  本发明涉及用于治疗性功能障碍的肟和腙的公式（I）化合物，以及含有用于治疗性功能障碍的公式（I）化合物的组合物。
• 1-Aryl-3-(4-pyridine-2-ylpiperazin-1-yl)propan-1-one Oximes as Potent Dopamine D₄ Receptor Agonists for the Treatment of Erectile Dysfunction
  作者：Teodozyj Kolasa、Mark A. Matulenko、Ahmed A. Hakeem、Meena V. Patel、Kathleen Mortell、Pramila Bhatia、Rodger Henry、Masaki Nakane、Gin C. Hsieh、Marc A. Terranova、Marie E. Uchic、Loan N. Miller、Renje Chang、Diana L. Donnelly-Roberts、Marian T. Namovic、Peter R. Hollingsworth、Brenda Martino、Odile El Kouhen、Kennan C. Marsh、Jill M. Wetter、Robert B. Moreland、Jorge D. Brioni、Andrew O. Stewart

  DOI：10.1021/jm060279f

  日期：2006.8.1

  A new series of dopamine D-4 receptor agonists, 1-aryl-3-(4-pyridinepiperazin-1-yl) propanone oximes, was designed through the modification of known dopamine D4 receptor agonist PD 168077. Replacement of the amide group with a methylene-oxime moiety produced compounds with improved stability and efficacy. Structure-activity relationsips (SAR) of the aromatic ring linked to the N-4-piperazine ring confirmed the superiority of 2-pyridine as a core for D4 agonist activity. A two-methylene linker between the oxime group and the N-1-piperazine ring displayed the best profile. New dopamine D4 receptor agonists, exemplified by (E)-1-(4-chlorophenyl)-3-(4-pyridin-2-ylpiperazin-1-yl) propan-1-one O-methyloxime (59a) and (E)-1-(3-chloro- 4-fluorophenyl)-3-(4-pyridin-2-ylpiperazin-1-yl) propan-1-one O-methyloxime (64a), exhibited favorable pharmacokinetic profiles and showed oral bioavailability in rat and dog. Subsequent evaluation of 59a in the rat penile erection model revealed in vivo activity, comparable in efficacy to apomorphine. Our results suggest that the oximes provide a novel structural linker for 4-arylpiperazine-based D4 agonists, possessing leadlike quality and with potential to develop a new class of potent and selective dopamine D4 receptor agonists.
• 2,3-Diketopiperazine as potential scaffold to develop new anti-Chagasic agents
  作者：Urbano Osorio-Nieto、Cristian O. Salas、Domingo Mendez-Alvarez、Gildardo Rivera、Adriana Moreno-Rodriguez、Yobana Perez-Cervera、Lizet Monserrat Castillo-Real、Christian Espinosa-Bustos

  DOI：10.1007/s00044-022-03003-9

  日期：2023.1

  of these compounds was determined in the murine macrophage J774 cell line, presenting in most cases, higher selectivity rates compared to Bzn and Nfx. In silico studies suggested that these 2,3-diketopiperazine derivatives could be inhibitors of the Fe-SOD enzyme at the cytosolic and mitochondrial level. Finally, these compounds would also have good oral bioavailability according to theoretical predictions

  继续我们开发具有潜在抗克氏锥虫活性的化合物的计划，在这项工作中，我们设计、合成并在体外对锥体鞭毛体进行了评估，形成了一系列新的 2,3-二酮哌嗪衍生物。通过两步序列，其中一步是催化和选择性 C( sp 3 )-H 键反应，获得了九种最终化合物 ( 5a-i )。 与参考药物苯并咪唑 (Bzn) 和硝呋替莫 (Nfx) 相比，这些 2,3-二酮哌嗪中的大多数对锥体鞭毛体菌株 NINOA 具有高活性（LC 50 < 100 μM）。同样，化合物5c和5h显示出对锥体鞭毛体菌株 A1 的高效力（LC50  = 25.2 和 40.49 μM，分别），其中5c的活性是参考药物的四到五倍。此外，这些化合物的细胞毒性是在小鼠巨噬细胞 J774 细胞系中测定的，在大多数情况下，与 Bzn 和 Nfx 相比，它们具有更高的选择性。计算机研究表明，这些 2,3-二酮哌嗪衍生物可能是细胞溶质和线粒体水平的 Fe-SOD