(3S,4S)-tert-butyl 3-((6-(bis(tert-butoxycarbonyl)amino)-4-methylpyridin-2-yl)methyl)-4-(2-oxoethoxy)pyrrolidine-1-carboxylate | 1367074-76-7

• 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: (3S,4S)-tert-butyl 3-((6-(bis(tert-butoxycarbonyl)amino)-4-methylpyridin-2-yl)methyl)-4-(2-oxoethoxy)pyrrolidine-1-carboxylate
• 英文别名: (3S,4S)-tert-Butyl 3-((6-(bis(tert-butoxycarbonyl)amino)-4-methylpyridin-2-yl)methyl)-4-(2-oxoethoxy)pyrrolidine-1-carboxylate；tert-butyl (3S,4S)-3-[[6-[bis[(2-methylpropan-2-yl)oxycarbonyl]amino]-4-methylpyridin-2-yl]methyl]-4-(2-oxoethoxy)pyrrolidine-1-carboxylate
• CAS: 1367074-76-7
• 化学式: C₂₈H₄₃N₃O₈
• 分子量: 549.665
• InChiKey: ZYQLLSBWLARRCO-PZJWPPBQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  39
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  125
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (3S,4S)-tert-butyl 3-((6-(bis(tert-butoxycarbonyl)amino)-4-methylpyridin-2-yl)methyl)-4-(2-oxoethoxy)pyrrolidine-1-carboxylate 在 盐酸 、 三乙酰氧基硼氢化钠 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 15.0h， 生成 2-((2-((3S,4S)-4-((6-amino-4-methylpyridin-2-yl)methyl)-pyrrolidin-3-yloxy)ethylamino)methyl)phenol
  参考文献：
  名称：

  Intramolecular hydrogen bonding: A potential strategy for more bioavailable inhibitors of neuronal nitric oxide synthase

  摘要：

  Selective neuronal nitric oxide synthase (nNOS) inhibitors have therapeutic applications in the treatment of numerous neurodegenerative diseases. Here we report the synthesis and evaluation of a series of inhibitors designed to have increased cell membrane permeability via intramolecular hydrogen bonding. Their potencies were examined in both purified enzyme and cell-based assays; a comparison of these results demonstrates that two of the new inhibitors display significantly increased membrane permeability over previous analogs. NMR spectroscopy provides evidence of intramolecular hydrogen bonding under physiological conditions in two of the inhibitors. Crystal structures of the inhibitors in the nNOS active site confirm the predicted non-intramolecular hydrogen bonded binding mode. Intramolecular hydrogen bonding may be an effective approach for increasing cell membrane permeability without affecting target protein binding. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.01.037
• 作为产物：
  描述：

  (3S,4S)-tert-butyl 3-(allyloxy)-4-((6-(bis(tert-butoxycarbonyl)amino)-4-methylpyridin-2-yl)methyl)pyrrolidine-1-carboxylate 在 臭氧 作用下， 以 二氯甲烷 为溶剂， 反应 0.67h， 以87%的产率得到(3S,4S)-tert-butyl 3-((6-(bis(tert-butoxycarbonyl)amino)-4-methylpyridin-2-yl)methyl)-4-(2-oxoethoxy)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Intramolecular Hydrogen-Bonded Nitric Oxide Synthase Inhibitors

  摘要：

  化合物和相关组合物及方法可用于选择性抑制神经一氧化氮合酶，并可用于治疗各种神经退行性疾病。

  公开号：

  US20120088798A1

文献信息

• Intramolecular Hydrogen-Bonded Nitric Oxide Synthase Inhibitors
  申请人：Silverman Richard B.

  公开号：US20120088798A1

  公开（公告）日：2012-04-12

  Compounds and related compositions and methods as can be used to selectively inhibit neuronal nitric oxide synthase and as can be employed in the treatment of various neurodegenerative diseases.

  化合物和相关组合物及方法可用于选择性抑制神经一氧化氮合酶，并可用于治疗各种神经退行性疾病。
• Intramolecular hydrogen-bonded nitric oxide synthase inhibitors
  申请人：Silverman Richard B.

  公开号：US08927730B2

  公开（公告）日：2015-01-06

  Compounds and related compositions and methods as can be used to selectively inhibit neuronal nitric oxide synthase and as can be employed in the treatment of various neurodegenerative diseases.

  化合物和相关组合物以及用于选择性抑制神经元一氧化氮合酶和用于治疗各种神经退行性疾病的方法。
• Intramolecular hydrogen bonding: A potential strategy for more bioavailable inhibitors of neuronal nitric oxide synthase
  作者：Kristin Jansen Labby、Fengtian Xue、James M. Kraus、Haitao Ji、Jan Mataka、Huiying Li、Pavel Martásek、Linda J. Roman、Thomas L. Poulos、Richard B. Silverman

  DOI：10.1016/j.bmc.2012.01.037

  日期：2012.4

  Selective neuronal nitric oxide synthase (nNOS) inhibitors have therapeutic applications in the treatment of numerous neurodegenerative diseases. Here we report the synthesis and evaluation of a series of inhibitors designed to have increased cell membrane permeability via intramolecular hydrogen bonding. Their potencies were examined in both purified enzyme and cell-based assays; a comparison of these results demonstrates that two of the new inhibitors display significantly increased membrane permeability over previous analogs. NMR spectroscopy provides evidence of intramolecular hydrogen bonding under physiological conditions in two of the inhibitors. Crystal structures of the inhibitors in the nNOS active site confirm the predicted non-intramolecular hydrogen bonded binding mode. Intramolecular hydrogen bonding may be an effective approach for increasing cell membrane permeability without affecting target protein binding. (C) 2012 Elsevier Ltd. All rights reserved.