3-(6-tert-butoxycarbonylamino-4-methyl-pyridin-2-ylmethyl)-4-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester | 848472-42-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 3-(6-tert-butoxycarbonylamino-4-methyl-pyridin-2-ylmethyl)-4-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester
• 英文别名: Tert-butyl 3-[[4-methyl-6-[(2-methylpropan-2-yl)oxycarbonylamino]pyridin-2-yl]methyl]-4-oxopyrrolidine-1-carboxylate
• CAS: 848472-42-4
• 化学式: C₂₁H₃₁N₃O₅
• 分子量: 405.494
• InChiKey: OBXUVNOXMPPNRP-UHFFFAOYSA-N

物化性质

• 沸点：
  497.4±45.0 °C(Predicted)
• 密度：
  1.191±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  97.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(6-tert-butoxycarbonylamino-4-methyl-pyridin-2-ylmethyl)-4-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester 在 盐酸 、 水 、 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 73.0h， 生成 N1-((+/-)-4'-[(6''-amino-4''-methylpyridin-2''-yl)methyl]pyrrolidin-3'-yl)-N2-(4'-chlorobenzyl)ethane-1,2-diamine tetrahydrochloride
  参考文献：
  名称：

  WO2008/42353

  摘要：

  公开号：
• 作为产物：
  描述：

  6-甲基吡啶-2-氨基甲酸叔丁酯 在 正丁基锂 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 23.75h， 生成 3-(6-tert-butoxycarbonylamino-4-methyl-pyridin-2-ylmethyl)-4-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  WO2008/42353

  摘要：

  公开号：

文献信息

• Discovery of Highly Potent and Selective Inhibitors of Neuronal Nitric Oxide Synthase by Fragment Hopping
  作者：Haitao Ji、Huiying Li、Pavel Martásek、Linda J. Roman、Thomas L. Poulos、Richard B. Silverman

  DOI：10.1021/jm801220a

  日期：2009.2.12

  appropriate lipophilic fragments for lead optimization. More potent and selective inhibitors with better druglike properties were obtained within the design of 20 derivatives (compounds 7−26). Our structure-based inhibitor design for nNOS and SAR analysis reveal the robustness and efficiency of fragment hopping in lead discovery and structural optimization, which implicates a broad application of this

  选择性抑制神经元一氧化氮合酶 (nNOS) 已被证明可以预防脑损伤，并且对于治疗各种神经退行性疾病很重要。该研究表明，通过片段跳跃不仅可以获得更高的抑制效力和同工酶选择性，而且可以获得更多的药物特性。基于先导分子6的结构，片段跳跃有效地提取了 nNOS 活性位点中最少的药效成分，用于配体疏水和空间相互作用，并生成合适的亲脂性片段用于先导优化。在 20 种衍生物（化合物7 - 26）。我们用于 nNOS 和 SAR 分析的基于结构的抑制剂设计揭示了片段跳跃在先导发现和结构优化中的稳健性和效率，这意味着这种方法可以广泛应用于许多其他治疗靶点，而这些治疗靶点已知的药物样小分子调节剂仍然有限.
• Heteroaromatic selective inhibitors of neuronal nitric oxide synthase
  申请人：Silverman B. Richard

  公开号：US20050107369A1

  公开（公告）日：2005-05-19

  Compounds inhibiting neuronal nitric oxide synthase (nNOS) for potential treatment in neurodegenerative diseases, such as stroke, Alzheimer's disease, Parkinson's disease, Huntington's disease, such compounds of a formula.

  抑制神经元一氧化氮合酶(nNOS)的化合物，用于潜在的神经退行性疾病治疗，如中风、阿尔茨海默病、帕金森病、亨廷顿病等，该化合物的公式为：
• Potent and highly selective heteroaromatic inhibitors of neuronal nitric oxide synthase
  申请人：Silverman B. Richard

  公开号：US20080108814A1

  公开（公告）日：2008-05-08

  Peptidomimetic compounds as can inhibit neuronal nitric oxide synthase (nNOS) for potential treatment in neurodegenerative diseases, such as but not limited to stroke, Alzheimer's disease, Parkinson's disease, Huntington's disease.

  肽类类似物化合物可抑制神经元一氧化氮合酶(nNOS)，用于潜在的治疗神经退行性疾病，如中风、阿尔茨海默病、帕金森病、亨廷顿病等。
• Heteroaromatic Selective Inhibitors of Neuronal Nitric Oxide Synthase
  申请人：Silverman Richard B.

  公开号：US20090104677A1

  公开（公告）日：2009-04-23

  Compounds inhibiting neuronal nitric oxide synthase (nNOS) for potential treatment in neurodegenerative diseases, such as stroke, Alzheimer's disease, Parkinson's disease, Huntington's disease, such compounds of a formula.

  抑制神经元一氧化氮合酶(nNOS)的化合物，用于潜在治疗神经退行性疾病，如中风、阿尔茨海默病、帕金森病、亨廷顿病等，这些化合物的公式为：
• Exploration of the Active Site of Neuronal Nitric Oxide Synthase by the Design and Synthesis of Pyrrolidinomethyl 2-Aminopyridine Derivatives
  作者：Haitao Ji、Silvia L. Delker、Huiying Li、Pavel Martásek、Linda J. Roman、Thomas L. Poulos、Richard B. Silverman

  DOI：10.1021/jm100947x

  日期：2010.11.11

  Neuronal nitric oxide synthase (nNOS) represents an important therapeutic target for the prevention of brain injury and the treatment of various neurodegenerative disorders. A series of trans-substituted amino pyrrolidinomethyl 2-aminopyridine derivatives (8-34) was designed and synthesized. A structure activity relationship analysis led to the discovery of low nanomolar nNOS inhibitors ((+/-)-32 and (+/-)-34) with more than 1000-fold selectivity for nNOS over eNOS. Four enantiomerically pure isomers of 3'-[2 ''-(3 ''-fluorophenethylamino)ethoxy]pyrrolidin-4'-yl}methyl}-4-methylpyridin-2-amine (4) also were synthesized. It was found that (3'R,4'R)-4 can induce enzyme elasticity to generate a new "hot spot" for ligand binding. The inhibitor adopts a unique binding mode, the same as that observed for (3'R,4'R)-3'-[2 ''-(3'''-fluorophenethylamino)ethylamino]pyrrolidin-4'-yl}methyl}-4-methylpyridin-2-amine ((3'R,4'R)-3) (J. Am. Chem. Soc. 2010, 132 (15), 5437-5442). On the basis of structure-activity relationships of 8-34 and different binding conformations of the cis and trans isomers of 3 and 4, critical structural requirements of the NOS active site for ligand binding are revealed.