2-(2,5-dimethyl-1H-pyrrol-1-yl)-6-((5-(1-(6-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methylpyridin-2-yl)-3-nitropropan-2-yl)pyridin-3-yl)ethynyl)-4-methylpyridine | 1609012-39-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(2,5-dimethyl-1H-pyrrol-1-yl)-6-((5-(1-(6-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methylpyridin-2-yl)-3-nitropropan-2-yl)pyridin-3-yl)ethynyl)-4-methylpyridine
• 英文别名: 2-(2,5-dimethylpyrrol-1-yl)-6-[2-[5-[2-[6-(2,5-dimethylpyrrol-1-yl)-4-methylpyridin-2-yl]ethynyl]pyridin-3-yl]-3-nitropropyl]-4-methylpyridine
• CAS: 1609012-39-6
• 化学式: C₃₄H₃₄N₆O₂
• 分子量: 558.683
• InChiKey: JSRLCCIOFOULCU-UHFFFAOYSA-N

物化性质

• 沸点：
  790.6±60.0 °C(predicted)
• 密度：
  1.18±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  42
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  94.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(2,5-dimethyl-1H-pyrrol-1-yl)-6-((5-(1-(6-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methylpyridin-2-yl)-3-nitropropan-2-yl)pyridin-3-yl)ethynyl)-4-methylpyridine 在 氢气 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 19.0h， 生成
  参考文献：
  名称：

  Nitric Oxide Synthase Inhibitors That Interact with Both Heme Propionate and Tetrahydrobiopterin Show High Isoform Selectivity

  摘要：

  Overproduction of NO by nNOS is implicated in the pathogenesis of diverse neuronal disorders. Since NO signaling is involved in diverse physiological functions, selective inhibition of nNOS over other isoforms is essential to minimize side effects. A series of alpha-amino functionalized aminopyridine derivatives (3-8) were designed to probe the structure activity relationship between ligand, heme propionate, and H4B. Compound 8R was identified as the most potent and selective molecule of this study, exhibiting a K-i of 24 nM for nNOS, with 273-fold and 2822-fold selectivity against iNOS and eNOS, respectively. Although crystal structures of 8R complexed with nNOS and eNOS revealed a similar binding mode, the selectivity stems from the distinct electrostatic environments in two isoforms that result in much lower inhibitor binding free energy in nNOS than in eNOS. These findings provide a basis for further development of simple, but even more selective and potent, nNOS inhibitors.

  DOI：

  10.1021/jm5004182
• 作为产物：
  描述：

  6-溴-4-甲基吡啶-2-胺 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 对甲苯磺酸 、 二乙胺 、 三苯基膦 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 1.66h， 生成 2-(2,5-dimethyl-1H-pyrrol-1-yl)-6-((5-(1-(6-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methylpyridin-2-yl)-3-nitropropan-2-yl)pyridin-3-yl)ethynyl)-4-methylpyridine
  参考文献：
  名称：

  Nitric Oxide Synthase Inhibitors That Interact with Both Heme Propionate and Tetrahydrobiopterin Show High Isoform Selectivity

  摘要：

  Overproduction of NO by nNOS is implicated in the pathogenesis of diverse neuronal disorders. Since NO signaling is involved in diverse physiological functions, selective inhibition of nNOS over other isoforms is essential to minimize side effects. A series of alpha-amino functionalized aminopyridine derivatives (3-8) were designed to probe the structure activity relationship between ligand, heme propionate, and H4B. Compound 8R was identified as the most potent and selective molecule of this study, exhibiting a K-i of 24 nM for nNOS, with 273-fold and 2822-fold selectivity against iNOS and eNOS, respectively. Although crystal structures of 8R complexed with nNOS and eNOS revealed a similar binding mode, the selectivity stems from the distinct electrostatic environments in two isoforms that result in much lower inhibitor binding free energy in nNOS than in eNOS. These findings provide a basis for further development of simple, but even more selective and potent, nNOS inhibitors.

  DOI：

  10.1021/jm5004182

文献信息

• Mammalian and Bacterial Nitric Oxide Synthase Inhibitors
  申请人：Northwestern University

  公开号：US20160122302A1

  公开（公告）日：2016-05-05

  Compounds and related methods for inhibition of mammalian and bacterial nitric oxide synthase.

  化合物及相关方法，用于抑制哺乳动物和细菌的一氧化氮合酶。
• Mammalian and bacterial nitric oxide synthase inhibitors
  申请人：Northwestern University

  公开号：US10759791B2

  公开（公告）日：2020-09-01

  Disclosed are compounds that are shown to inhibit the biological activity of nitric oxide synthases (NOSs). Also disclosed are pharmaceutical compositions comprising the compounds, and methods of using the compounds and pharmaceutical compositions for treating a subject in need thereof. Because the disclosed compounds are shown to inhibit the activity of nitric oxide synthases (NOSs), the disclosed compounds and pharmaceutical compositions may be utilized in methods for treating a subject having or at risk for developing a disease or disorder that is associated with NOS activity.

  所公开的化合物被证明可抑制一氧化氮合酶（NOSs）的生物活性。还公开了包含这些化合物的药物组合物，以及使用这些化合物和药物组合物治疗有需要的受试者的方法。由于所公开的化合物被证明可抑制一氧化氮合酶（NOSs）的活性，因此所公开的化合物和药物组合物可用于治疗患有或有可能患有与 NOS 活性相关的疾病或紊乱的受试者的方法中。
• MAMMALIAN AND BACTERIAL NITRIC OXIDE SYNTHASE INHIBITORS
  申请人：Northwestern University

  公开号：EP3215497A2

  公开（公告）日：2017-09-13
• US9951014B2
  申请人：——

  公开号：US9951014B2

  公开（公告）日：2018-04-24
• [EN] MAMMALIAN AND BACTERIAL NITRIC OXIDE SYNTHASE INHIBITORS<br/>[FR] INHIBITEURS D'OXYDE NITRIQUE SYNTHASE D'ORIGINE BACTÉRIENNE ET MAMMALIENNE
  申请人：UNIV NORTHWESTERN

  公开号：WO2016073623A2

  公开（公告）日：2016-05-12

  Compounds and related methods for inhibition of mammalian and bacterial nitric oxide synthase.