2-甲基-3-(1-哌嗪基)吡嗪 | 93263-83-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 2-甲基-3-(1-哌嗪基)吡嗪
• 英文名称: 2-methyl-3-(piperazin-1-yl)pyrazine
• 英文别名: 3-Piperazino-2-methylpyrazin；1-(3-Methylpyrazin-2-yl)-piperazin；3'-methyl-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl；2-methyl-3-piperazin-1-ylpyrazine
• CAS: 93263-83-3
• 化学式: C₉H₁₄N₄
• mdl: MFCD20663142
• 分子量: 178.237
• InChiKey: UIYIEUWPSAMPNA-UHFFFAOYSA-N

物化性质

• 沸点：
  115-117 °C(Press: 0.3 Torr)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.555
• 拓扑面积：
  41
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  5-(6-oxo-1,6-dihydropyridazin-3-yl)thiophene-2-sulfonyl chloride 、 2-甲基-3-(1-哌嗪基)吡嗪 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以64 %的产率得到MBX-4055
  参考文献：
  名称：

  Optimized pyridazinone nutrient channel inhibitors are potent and specific antimalarial leads

  摘要：

  人类和动物疟原虫寄生虫通过寄生虫相关离子通道，增加宿主红细胞对多种溶质的通透性。分子和药理学研究表明，寄生虫营养获取过程中寄生虫发挥着重要作用，但适合开发抗疟药物的抑制剂尚未出现。在此，我们使用恶性疟原虫（一种致命的人类病原体）和MBX-2366衍生物（一种从高通

  DOI：

  10.1124/molpharm.122.000549

文献信息

• [EN] OGA INHIBITOR COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS D'OGA
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2021123291A1

  公开（公告）日：2021-06-24

  The present invention relates to O-GlcNAc hydrolase (OGA) inhibitors. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which inhibition of OGA is beneficial, such as tauopathies, in particular Alzheimer's disease or progressive supranuclear palsy; and neurodegenerative diseases accompanied by a tau pathology, in particular amyotrophic lateral sclerosis or frontotemporal lobe dementia caused by C9ORF72 mutations; or alpha synucleinopathies, in particular Parkinson's disease, dementia due to Parkinson's (or neurocognitive disorder due to Parkinson's disease), dementia with Lewy bodies, multiple system atrophy, or alpha synucleinopathy caused by Gaucher's disease.

  本发明涉及O-GlcNAc水解酶（OGA）抑制剂。该发明还涉及包含这类化合物的药物组合物，制备这类化合物和组合物的方法，以及利用这类化合物和组合物预防和治疗抑制OGA有益的疾病的用途，例如tau病变，特别是阿尔茨海默病或进行性上行性核瘫痪；以及伴有tau病理的神经退行性疾病，特别是由C9ORF72突变引起的肌萎缩侧索硬化或额颞叶痴呆；或α-突触核蛋白病，特别是帕金森病、帕金森病引起的痴呆（或由帕金森病引起的神经认知障碍）、带有Lewy小体的痴呆、多系统萎缩，或由高雪氏病引起的α-突触核蛋白病。
• Optimized pyridazinone nutrient channel inhibitors are potent and specific antimalarial leads
  作者：Michelle M Butler、Samanthi L. Waidyarachchi、Jinfeng Shao、Son T. Nguyen、Xiaoyuan Ding、Steven C. Cardinale、Lucas R. Morin、Steven M. Kwasny、Mai Ito、Jeanine Gezelle、Maria B. Jiminez-Di­az、Inigo Angulo-Barturen、Robert T. Jacobs、Jeremy N. Burrows、Zachary D. Aron、Terry L. Bowlin、Sanjay A. Desai

  DOI：10.1124/molpharm.122.000549

  日期：——

  Human and animal malaria parasites increase their host erythrocyte permeability to a broad range of solutes as mediated by parasite-associated ion channels. Molecular and pharmacological studies have implicated an essential role in parasite nutrient acquisition, but inhibitors suitable for development of antimalarial drugs are missing. Here, we generated a potent and specific drug lead using Plasmodium falciparum , a virulent human pathogen, and derivatives of MBX-2366, a nanomolar affinity pyridazinone inhibitor from a high-throughput screen. As this screening hit lacks the bioavailability and stability needed for in vivo efficacy, we synthesized 315 derivatives to optimize drug-like properties, establish target specificity, and retain potent activity against the parasite-induced permeability. Using a robust, iterative pipeline, we generated MBX-4055, a derivative active against divergent human parasite strains. MBX-4055 has improved oral absorption with acceptable in vivo tolerability and pharmacokinetics. It also has no activity against a battery of 35 human channels and receptors and is refractory to acquired resistance during extended in vitro selection. Single-molecule and single-cell patch-clamp indicate direct action on the plasmodial surface anion channel, a channel linked to parasite-encoded RhopH proteins. These studies identify pyridazinones as novel and tractable antimalarial scaffolds with a defined mechanism of action. SIGNIFICANCE STATEMENT Because antimalarial drugs are prone to evolving resistance in the virulent human P. falciparum pathogen, new therapies are needed. This study has now developed a novel drug-like series of pyridazinones that target an unexploited parasite anion channel on the host cell surface, display excellent in vitro and in vivo ADME properties, are refractory to acquired resistance, and demonstrate a well defined mechanism of action.

  人类和动物疟原虫寄生虫通过寄生虫相关离子通道，增加宿主红细胞对多种溶质的通透性。分子和药理学研究表明，寄生虫营养获取过程中寄生虫发挥着重要作用，但适合开发抗疟药物的抑制剂尚未出现。在此，我们使用恶性疟原虫（一种致命的人类病原体）和MBX-2366衍生物（一种从高通