Tert-butyl 4-[3,5-bis[2-(6-amino-4-methylpyridin-2-yl)ethyl]phenyl]piperazine-1-carboxylate | 1422268-70-9

• 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: Tert-butyl 4-[3,5-bis[2-(6-amino-4-methylpyridin-2-yl)ethyl]phenyl]piperazine-1-carboxylate
• 英文别名: tert-butyl 4-[3,5-bis[2-(6-amino-4-methylpyridin-2-yl)ethyl]phenyl]piperazine-1-carboxylate
• CAS: 1422268-70-9
• 化学式: C₃₁H₄₂N₆O₂
• 分子量: 530.713
• InChiKey: LYZFPJQCPDEVAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Tert-butyl 4-[3,5-bis[2-(6-amino-4-methylpyridin-2-yl)ethyl]phenyl]piperazine-1-carboxylate 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以58%的产率得到6-[2-[3-[2-(6-Amino-4-methylpyridin-2-yl)ethyl]-5-piperazin-1-ylphenyl]ethyl]-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：

  5-溴间二溴苄 在 tris-(dibenzylideneacetone)dipalladium(0) 、 正丁基锂 、 盐酸羟胺 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 水 、 甲苯 为溶剂， 反应 8.67h， 生成 Tert-butyl 4-[3,5-bis[2-(6-amino-4-methylpyridin-2-yl)ethyl]phenyl]piperazine-1-carboxylate
  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。
• US8932842B2
  申请人：——

  公开号：US8932842B2

  公开（公告）日：2015-01-13
• Structure-Guided Design of Selective Inhibitors of Neuronal Nitric Oxide Synthase
  作者：He Huang、Huiying Li、Pavel Martásek、Linda J. Roman、Thomas L. Poulos、Richard B. Silverman

  DOI：10.1021/jm4000984

  日期：2013.4.11

  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.