2-溴-6-(2,5-二甲基-1H-吡咯-1-基)-4-甲基-吡啶 | 771530-89-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 2-溴-6-(2,5-二甲基-1H-吡咯-1-基)-4-甲基-吡啶
• 英文名称: 2-bromo-6-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methylpyridine
• 英文别名: 2-bromo-6-(2,5-dimethylpyrrol-1-yl)-4-methylpyridine
• CAS: 771530-89-3
• 化学式: C₁₂H₁₃BrN₂
• 分子量: 265.153
• InChiKey: UPKZQRDTGPBVPM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-溴-6-(2,5-二甲基-1H-吡咯-1-基)-4-甲基-吡啶 在 盐酸 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 氢气 、 二乙胺 、 三苯基膦 作用下， 以 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.99h， 生成 6-(3-amino-2-(6-(2-(6-amino-4-methylpyridin-2-yl)ethyl)pyridin-2-yl)propyl)-4-methylpyridin-2-amine
  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：

  3-羟基-3-甲基戊二腈 在 氢溴酸 、 对甲苯磺酸 、 溶剂黄146 作用下， 以 甲苯 为溶剂， 反应 3.5h， 生成 2-溴-6-(2,5-二甲基-1H-吡咯-1-基)-4-甲基-吡啶
  参考文献：
  名称：

  Arylmethoxypyridines as novel, potent and orally active mGlu5 receptor antagonists

  摘要：

  Optimisation of affinity, chemical stability, metabolic stability and solubility led from a chemically labile HTS hit 1 to mGlu5 receptor antagonists (24-26) with high affinity for the allosteric M PEP binding site, improved microsomal metabolic stability and anxiolytic-like activity in vivo as assessed by the Vogel conflict drinking test. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.12.088

文献信息

• [EN] NOVEL 6-SUBSTITUTED 2-AMINOPYRIDINE DERIVATIVES<br/>[FR] NOUVEAUX DERIVES DE 2-AMINOPYRIDINE SUBSTITUEE EN 6
  申请人：ASTRAZENECA AB

  公开号：WO2004087665A1

  公开（公告）日：2004-10-14

  There are provided novel compounds of formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, L1, L2, L3 and Q are are as defined in the specification, and pharmaceutically acceptable salts thereof; together with processes for their preparation, compositions containing them and their use in therapy. The compounds are inhibitors of nitric oxide synthase and are thereby particularly useful in the treatment or prophylaxis of inflammatory disease and pain.

  提供了式（I）的新化合物，其中R1、R2、R3、R4、R5、R6、R7、R8、R9、L1、L2、L3和Q如规范中所定义，并且其药用盐；以及它们的制备方法、含有它们的组合物以及它们在治疗中的应用。这些化合物是一氧化氮合酶的抑制剂，因此在炎症性疾病和疼痛的治疗或预防中特别有用。
• Novel 6-substituted 2-aminopyridine derivatives
  申请人：Cheshire David

  公开号：US20060194847A1

  公开（公告）日：2006-08-31

  There are provided novel compounds of formula (I) wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , L 1 , L 2 , L 3 and Q are are as defined in the specification, and pharmaceutically acceptable salts thereof; together with processes for their preparation, compositions containing them and their use in therapy. The compounds are inhibitors of nitric oxide synthase and are thereby particularly useful in the treatment or prophylaxis of inflammatory disease and pain.

  提供了式（I）的新化合物，其中R1、R2、R3、R4、R5、R6、R7、R8、R9、L1、L2、L3和Q如规范中所定义，并且它们的药学上可接受的盐；以及它们的制备过程、含有它们的组合物和它们在治疗中的应用。这些化合物是一氧化氮合酶抑制剂，因此在治疗或预防炎症性疾病和疼痛方面特别有用。
• 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。
• [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：WO2016073623A3

  公开（公告）日：2016-10-27