6-(4-(2-(4-isopropylphenyl)acetyl)piperazin-1-yl)pyridazine-3-carbonitrile

• 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: 6-(4-(2-(4-isopropylphenyl)acetyl)piperazin-1-yl)pyridazine-3-carbonitrile
• 英文别名: 6-(4-(2-(4-Isopropylphenyl)acetyl)piperazin-1-yl)pyridazine-3-carbonitrile；6-[4-[2-(4-propan-2-ylphenyl)acetyl]piperazin-1-yl]pyridazine-3-carbonitrile
• 化学式: C₂₀H₂₃N₅O
• 分子量: 349.436
• InChiKey: LGWDVWIZDPGCFG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  73.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-异丙基苯乙酸 在 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 1.5h， 生成 6-(4-(2-(4-isopropylphenyl)acetyl)piperazin-1-yl)pyridazine-3-carbonitrile
  参考文献：
  名称：

  LipE 指导发现异丙基苯基哒嗪作为泛酸激酶调节剂

  摘要：

  泛酸激酶 (PANK) 是细胞内辅酶 A 水平的关键调节剂，已成为治疗神经和代谢疾病的有吸引力的靶标。本报告描述了一种新化学系列泛酸竞争性 PANK 抑制剂的优化、合成和完整的构效关系。使用源自人 PANK3 IC 50的亲脂性配体效率 (LipE) 通过优化高通量筛选命中获得有效的药物样分子指导配体开发的价值。确定了具有优化指数抑制剂的 PANK3 的 X 射线晶体结构，以合理化新出现的结构活性关系。分析揭示了哒嗪和 R306' 之间的关键双齿氢键相互作用是优化中观察到的 LipE 增益的主要贡献者。本研究产生了一系列易于处理的 PANK3 调节剂，具有纳摩尔效力、优异的 LipE 值、理想的物理化学性质和明确的结构结合模式。

  DOI：

  10.1016/j.bmc.2021.116504

文献信息

• Small molecule modulators of pantothenate kinases
  申请人：St. Jude Children's Research Hospital

  公开号：US10899734B2

  公开（公告）日：2021-01-26

  The present disclosure relates to chemical compounds that modulate pantothenate kinase (PanK) activity for the treatment of metabolic disorders (such as diabetes mellitus type II), neurologic disorders (such as pantothenate kinase-associated neurodegeneration), pharmaceutical compositions containing such compounds, and their use in treatment. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  本公开涉及调节泛酸激酶（PanK）活性以治疗代谢紊乱（如 II 型糖尿病）、神经紊乱（如泛酸激酶相关神经变性）的化学化合物、含有此类化合物的药物组合物及其在治疗中的用途。本摘要旨在作为在特定技术领域进行搜索的扫描工具，并非对本发明的限制。
• SMALL MOLECULE MODULATORS OF PANTOTHENATE KINASES
  申请人：St. Jude Children's Research Hospital, Inc.

  公开号：EP3474667A1

  公开（公告）日：2019-05-01
• METHODS OF TREATING DISORDERS ASSOCIATED WITH CASTOR
  申请人：ST. JUDE CHILDREN'S RESEARCH HOSPITAL, INC.

  公开号：US20210023081A1

  公开（公告）日：2021-01-28

  The present disclosure relates to methods of treating a coenzyme A reduction, elevation, sequestration, toxicity, or redistribution (CASTOR) disease such as, for example, defects in fatty acid oxidation enzymes, methylmalonic acidemia, glutaric acidemia, propionic academia, and HMG-CoA lyase, via small molecule modulators of CoA levels. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
• [EN] SMALL MOLECULE MODULATORS OF PANTOTHENATE KINASES<br/>[FR] MODULATEURS À PETITES MOLÉCULES DES PANTOTHÉNATE KINASES
  申请人：ST JUDE CHILDREN'S RES HOSPITAL

  公开号：WO2017223474A1

  公开（公告）日：2017-12-28

  The present disclosure relates to chemical compounds that modulate pantothenate kinase (PanK) activity for the treatment of metabolic disorders (such as diabetes mellitus type II), neurologic disorders (such as pantothenate kinase-associated neurodegeneration), pharmaceutical compositions containing such compounds, and their use in treatment. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
• [EN] METHODS OF TREATING DISORDERS ASSOCIATED WITH CASTOR<br/>[FR] MÉTHODES DE TRAITEMENT DE TROUBLES ASSOCIÉS À CASTOR
  申请人：[en]ST. JUDE CHILDREN'S RESEARCH HOSPITAL, INC.

  公开号：WO2022133034A1

  公开（公告）日：2022-06-23

  The present disclosure relates to methods of identifying subjects in need of treatment for, e.g., a coenzyme A reduction, elevation, sequestration, toxicity, or redistribution (CASTOR) disease such as, for example, defects in fatty acid oxidation enzymes, methylmalonic acidemia, glutaric acidemia, propionic academia, and HMG-CoA lyase, via small molecule modulators of CoA levels. The methods may comprise assessing levels of carnitines, CoA, and/or various metabolites and biomarkers and administration of therapeutics useful in the treatment of CASTOR disorders, metabolic diseases, and/or neurological diseases. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present inventions.