(2S,4R)-tert-butyl 4-(3-(thiophene-2-carboximidamido)phenoxy)-2-(((3-fluorobenzyl)oxy)methyl)pyrrolidine-1-carboxylate | 1572937-42-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S,4R)-tert-butyl 4-(3-(thiophene-2-carboximidamido)phenoxy)-2-(((3-fluorobenzyl)oxy)methyl)pyrrolidine-1-carboxylate
• 英文别名: tert-butyl (2S,4R)-4-[3-[[amino(thiophen-2-yl)methylidene]amino]phenoxy]-2-[(3-fluorophenyl)methoxymethyl]pyrrolidine-1-carboxylate
• CAS: 1572937-42-8
• 化学式: C₂₈H₃₂FN₃O₄S
• 分子量: 525.644
• InChiKey: JKYUWOIULQKJIG-LADGPHEKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  115
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S,4R)-tert-butyl 4-(3-(thiophene-2-carboximidamido)phenoxy)-2-(((3-fluorobenzyl)oxy)methyl)pyrrolidine-1-carboxylate 在 盐酸 作用下， 以 甲醇 为溶剂， 以85%的产率得到N-(3-(((2S,4R)-4-(((3-fluorobenzyl)oxy)methyl)pyrrolidin-2-yl)oxy)phenyl)thiophene-2-carboximidamide
  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：

  (2S,4R)-tert-butyl 2-(((3-fluorobenzyl)oxy)methyl)-4-(3-nitrophenoxy)pyrrolidine-1-carboxylate 在 一水合肼 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 27.0h， 生成 (2S,4R)-tert-butyl 4-(3-(thiophene-2-carboximidamido)phenoxy)-2-(((3-fluorobenzyl)oxy)methyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Combination of chiral linkers with thiophenecarboximidamide heads to improve the selectivity of inhibitors of neuronal nitric oxide synthase

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2014.07.079

文献信息

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

  公开号：US20160152590A1

  公开（公告）日：2016-06-02

  Selective neuronal nitric oxide synthase (nNOS) inhibitor compounds designed with one or more thiophene-2-carboximidamide substituents for improved bioavailability.
• US9682950B2
  申请人：——

  公开号：US9682950B2

  公开（公告）日：2017-06-20