3,5-bis(2-(6-amino-4-methylpyridin-2-yl)ethyl)benzonitrile | 1422268-60-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3,5-bis(2-(6-amino-4-methylpyridin-2-yl)ethyl)benzonitrile
• 英文别名: 3,5-Bis[2-(6-Amino-4-Methylpyridin-2-Yl)ethyl]benzonitrile；3,5-bis[2-(6-amino-4-methylpyridin-2-yl)ethyl]benzonitrile
• CAS: 1422268-60-7
• 化学式: C₂₃H₂₅N₅
• 分子量: 371.485
• InChiKey: IXUSJKAERUMZME-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,5-bis(2-(6-amino-4-methylpyridin-2-yl)ethyl)benzonitrile 在 锂硼氢 、 三甲基氯硅烷 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以42%的产率得到6,6'-((5-(aminomethyl)-1,3-phenylene)bis(ethane-2,1-diyl))bis(4-methylpyridin-2-amine)
  参考文献：
  名称：

  Structure-Guided Design of Selective Inhibitors of Neuronal Nitric Oxide Synthase

  摘要：

  Nitric oxide synthases (NOSs) comprise three closely related isoforms that catalyze the oxidation of L-arginine to L-citrulline and the important second messenger nitric oxide (NO). Pharmacological selective inhibition of neuronal NOS (nNOS) has the potential to be therapeutically beneficial in various neurodegenerative diseases. Here, we present a structure-guided, selective nNOS inhibitor design based on the crystal structure of lead compound 1 in nNOS. The best inhibitor, 7, exhibited low nanomolar inhibitory potency and good isoform selectivities (nNOS over eNOS and iNOS are 472-fold and 239-fold, respectively). Consistent with the good selectivity, 7 binds to nNOS and eNOS with different binding modes. The distinctly different binding modes of 7, driven by the critical residue Asp597 in nNOS, offers compelling insight to explain its isozyme selectivity, which should guide future drug design programs.

  DOI：

  10.1021/jm4000984
• 作为产物：
  描述：

  3,5-二甲基苯腈 在 N-溴代丁二酰亚胺(NBS) 、 正丁基锂 、 盐酸羟胺 、 过氧化苯甲酰 作用下， 以 四氢呋喃 、 四氯化碳 、 乙醇 、 正己烷 、 水 为溶剂， 反应 30.67h， 生成 3,5-bis(2-(6-amino-4-methylpyridin-2-yl)ethyl)benzonitrile
  参考文献：
  名称：

  Structure-Guided Design of Selective Inhibitors of Neuronal Nitric Oxide Synthase

  摘要：

  Nitric oxide synthases (NOSs) comprise three closely related isoforms that catalyze the oxidation of L-arginine to L-citrulline and the important second messenger nitric oxide (NO). Pharmacological selective inhibition of neuronal NOS (nNOS) has the potential to be therapeutically beneficial in various neurodegenerative diseases. Here, we present a structure-guided, selective nNOS inhibitor design based on the crystal structure of lead compound 1 in nNOS. The best inhibitor, 7, exhibited low nanomolar inhibitory potency and good isoform selectivities (nNOS over eNOS and iNOS are 472-fold and 239-fold, respectively). Consistent with the good selectivity, 7 binds to nNOS and eNOS with different binding modes. The distinctly different binding modes of 7, driven by the critical residue Asp597 in nNOS, offers compelling insight to explain its isozyme selectivity, which should guide future drug design programs.

  DOI：

  10.1021/jm4000984

文献信息

• Aminopyridine dimer compounds, compositions and related methods for neuronal nitric oxide synthase inhibition
  申请人：Northwestern University

  公开号：US20130040359A1

  公开（公告）日：2013-02-14

  Nitric oxide synthase (NOS) inhibitor compounds comprising bi-terminal aromatic ring moieties, and related methods of NOS inhibition.

  一氧化氮合酶（NOS）抑制剂化合物包括具有双末端芳香环基团的化合物，并且相关的NOS抑制方法。
• 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。
• US8932842B2
  申请人：——

  公开号：US8932842B2

  公开（公告）日：2015-01-13
• US9951014B2
  申请人：——

  公开号：US9951014B2

  公开（公告）日：2018-04-24