tert-butyl 2-(4-hydroxyphenyl)propylcarbamate | 942593-71-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: tert-butyl 2-(4-hydroxyphenyl)propylcarbamate
• 英文别名: tert-butyl N-[2-(4-hydroxyphenyl)propyl]carbamate
• CAS: 942593-71-7
• 化学式: C₁₄H₂₁NO₃
• 分子量: 251.326
• InChiKey: YMRVBNKNTABOOZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-(4-hydroxyphenyl)propylcarbamate 在 N,N-二异丙基乙胺 吡啶 、 盐酸 、 copper diacetate 、 4 A molecular sieve 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 24.0h， 生成 2-(4-Phenoxyphenyl)propylazanium;chloride
  参考文献：
  名称：

  Exploring the Structure−Activity Relationship of the Ethylamine Portion of 3-Iodothyronamine for Rat and Mouse Trace Amine-Associated Receptor 1

  摘要：

  3-Iodothyronamine (1, T(1)AM) is a naturally occurring derivative of thyroid hormone that can potently activate the orphan G protein-coupled receptor (GPCR) known as the trace amine-associated receptor 1 (TAAR(1)). We have previously found that modifying the outer ring of the phenoxyphenethylamine core scaffold of 1 can improve potency and provide potent agonists. In this study, we explored the tolerance of rat and mouse TAAR(1) (rTAAR(1) and mTAAR(1)) for structural modifications in the ethylamine portion of 1. We found that incorporating unsaturated hydrocarbon substituents and polar, hydrogen-bond-accepting groups were beneficial for rTAAR(1) and mTAAR(1), respectively, providing compounds that were equipotent or more potent than 1. Additionally, we have discovered that a naphthyl group is an excellent isosteric replacement for the iodophenyl ring of 1.

  DOI：

  10.1021/jm0700417
• 作为产物：
  描述：

  2-(4-(triisopropyl)silyloxyphenyl)acetonitrile 在 lithium aluminium tetrahydride 、 四丁基氟化铵 、 碳酸氢钠 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正庚烷 、 乙基苯 为溶剂， 反应 26.0h， 生成 tert-butyl 2-(4-hydroxyphenyl)propylcarbamate
  参考文献：
  名称：

  Exploring the Structure−Activity Relationship of the Ethylamine Portion of 3-Iodothyronamine for Rat and Mouse Trace Amine-Associated Receptor 1

  摘要：

  3-Iodothyronamine (1, T(1)AM) is a naturally occurring derivative of thyroid hormone that can potently activate the orphan G protein-coupled receptor (GPCR) known as the trace amine-associated receptor 1 (TAAR(1)). We have previously found that modifying the outer ring of the phenoxyphenethylamine core scaffold of 1 can improve potency and provide potent agonists. In this study, we explored the tolerance of rat and mouse TAAR(1) (rTAAR(1) and mTAAR(1)) for structural modifications in the ethylamine portion of 1. We found that incorporating unsaturated hydrocarbon substituents and polar, hydrogen-bond-accepting groups were beneficial for rTAAR(1) and mTAAR(1), respectively, providing compounds that were equipotent or more potent than 1. Additionally, we have discovered that a naphthyl group is an excellent isosteric replacement for the iodophenyl ring of 1.

  DOI：

  10.1021/jm0700417

文献信息

• Multiple binding modes of isothiocyanates that inhibit macrophage migration inhibitory factor
  作者：Emma S. Spencer、Edward J. Dale、Aimée L. Gommans、Malcolm T. Rutledge、Christine T. Vo、Yoshio Nakatani、Allan B. Gamble、Robin A.J. Smith、Sigurd M. Wilbanks、Mark B. Hampton、Joel D.A. Tyndall

  DOI：10.1016/j.ejmech.2015.02.012

  日期：2015.3

  Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that has roles in the innate immune response, and also contributes to inflammatory disease. While the biological properties of MIF are closely linked to protein protein interactions, MW also has tautomerase activity. Inhibition of this activity interferes with the interaction of MIF with protein partners e.g. the CD74 receptor, and tautomerase inhibitors show promise in disease models including multiple sclerosis and colitis. Isothiocyanates inhibit MIF tautomerase activity via covalent modification of the N-terminal proline. We systematically explored variants of benzyl and phenethyl isothiocyanates, to define determinants of inhibition. In particular, substitution with hydroxyl, chloro, fluoro and trifluoro moieties at the para and meta positions were evaluated. In assays on treated cells and recombinant protein, the IC50 varied from 250 nM to >100 mu M. X-ray crystal structures of selected complexes revealed that two binding modes are accessed by some compounds, perhaps owing to strain in short linkers between the isothiocyanate and aromatic ring. The variety of binding modes confirms the existence of two subsites for inhibitors and establishes a platform for the development of potent inhibitors of MIF that only need to target one of these subsites. (C) 2015 Elsevier Masson SAS. All rights reserved.