(2S,4R)-1-tert-butyl 2-methyl 4-((3-fluorobenzyl)oxy)pyrrolidine-1,2-dicarboxylate | 1143524-44-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S,4R)-1-tert-butyl 2-methyl 4-((3-fluorobenzyl)oxy)pyrrolidine-1,2-dicarboxylate
• 英文别名: 1-O-tert-butyl 2-O-methyl (2S,4R)-4-[(3-fluorophenyl)methoxy]pyrrolidine-1,2-dicarboxylate
• CAS: 1143524-44-0
• 化学式: C₁₈H₂₄FNO₅
• 分子量: 353.391
• InChiKey: JAYVPISWFHKHQB-CABCVRRESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,4R)-1-tert-butyl 2-methyl 4-((3-fluorobenzyl)oxy)pyrrolidine-1,2-dicarboxylate 在 锂硼氢 、 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 生成 (2S,4R)-tert-butyl 4-((3-fluorobenzyl)oxy)-2-((3-nitrophenoxy)methyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Thiophene-2-carboximidamide Based Selective Neuronal Nitric Oxide Inhibitors

  摘要：

  选择性神经型一氧化氮合酶（nNOS）抑制剂化合物设计为具有一个或多个噻吩-2-羧酰胺取代基，以提高生物利用度。

  公开号：

  US20140066635A1
• 作为产物：
  描述：

  N-Boc-反式-4-羟基-L-脯氨酸甲酯 、 3-氟溴苄 在 sodium hydride 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以68%的产率得到(2S,4R)-1-tert-butyl 2-methyl 4-((3-fluorobenzyl)oxy)pyrrolidine-1,2-dicarboxylate
  参考文献：
  名称：

  Thiophene-2-carboximidamide Based Selective Neuronal Nitric Oxide Inhibitors

  摘要：

  选择性神经型一氧化氮合酶（nNOS）抑制剂化合物设计为具有一个或多个噻吩-2-羧酰胺取代基，以提高生物利用度。

  公开号：

  US20140066635A1

文献信息

• Thiophene-2-carboximidamide Based Selective Neuronal Nitric Oxide Inhibitors
  申请人：Silverman Richard B.

  公开号：US20140066635A1

  公开（公告）日：2014-03-06

  Selective neuronal nitric oxide synthase (nNOS) inhibitor compounds designed with one or more thiophene-2-carboximidamide substituents for improved bioavailability.

  选择性神经型一氧化氮合酶（nNOS）抑制剂化合物设计为具有一个或多个噻吩-2-羧酰胺取代基，以提高生物利用度。
• Combination of chiral linkers with thiophenecarboximidamide heads to improve the selectivity of inhibitors of neuronal nitric oxide synthase
  作者：Qing Jing、Huiying Li、Linda J. Roman、Pavel Martásek、Thomas L. Poulos、Richard B. Silverman

  DOI：10.1016/j.bmcl.2014.07.079

  日期：2014.9

  To develop potent and selective nNOS inhibitors, a new series of double-headed molecules with chiral linkers that derive from natural amino acid derivatives have been designed and synthesized. The new structures integrate a thiophenecarboximidamide head with two types of chiral linkers, presenting easy synthesis and good inhibitory properties. Inhibitor (S)-9b exhibits a potency of 14.7 nM against nNOS and is 1134 and 322-fold more selective for nNOS over eNOS and iNOS, respectively. Crystal structures show that the additional binding between the aminomethyl moiety of 9b and propionate A on the heme and tetrahydrobiopterin (H4B) in nNOS, but not eNOS, contributes to its high selectivity. This work demonstrates the advantage of integrating known structures into structure optimization, and it should be possible to more readily develop compounds that incorporate bioavailability with these advanced features. Moreover, this integrative strategy is a general approach in new drug discovery. (C) 2014 Elsevier Ltd. All rights reserved.