(R)-tert-butyl (2-(1,3-dioxoisoindolin-2-yl)-1-phenylethyl)carbamate | 224633-13-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: (R)-tert-butyl (2-(1,3-dioxoisoindolin-2-yl)-1-phenylethyl)carbamate
• 英文别名: (R)-N-(tert-butoxycarbonyl)-α-(phthalimidomethyl)benzylamine；[(R)-2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-1-phenylethyl]-carbamic acid tert-butyl ester；tert-butyl N-[(1R)-2-(1,3-dioxoisoindol-2-yl)-1-phenylethyl]carbamate
• CAS: 224633-13-0
• 化学式: C₂₁H₂₂N₂O₄
• 分子量: 366.417
• InChiKey: OYZAHCPZEWWFDO-KRWDZBQOSA-N

物化性质

• 沸点：
  539.8±50.0 °C(Predicted)
• 密度：
  1.235±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-tert-butyl (2-(1,3-dioxoisoindolin-2-yl)-1-phenylethyl)carbamate 在 盐酸 、 potassium carbonate 、 一水合肼 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.75h， 生成 2-Phenyl-quinoline-4-carboxylic acid ((S)-2-amino-1-phenyl-ethyl)-amide
  参考文献：
  名称：

  Discovery of a Novel Class of Selective Non-Peptide Antagonists for the Human Neurokinin-3 Receptor. 2. Identification of (S)-N-(1-Phenylpropyl)-3-hydroxy-2- phenylquinoline-4-carboxamide (SB 223412)

  摘要：

  Optimization of the previously reported 2-phenyl-4-quinolinecarboxamide NK-3 receptor antagonist 14, with regard to potential metabolic instability of the ester moiety and affinity and selectivity for the human neurokinin-3 (hNK-3) receptor, is described. The ester functionality could be successfully replaced by the ketone (31) or by lower alkyl groups (Et, 21, or n-Pr, 24). Investigation of the substitution pattern of the quinoline ring resulted in the identification of position 3 as a key position to enhance hNK-3 binding affinity and selectivity for the hNK-3 versus the hNK-2 receptor. All of the chemical groups introduced at this position, with the exception of halogens, increased the hNK-3 binding affinity, and compounds 53 (3-OH, SE 223412, hNK-3-CHO binding K-i = 1.4 nM) and 55 (3-NHz, hNK-3-CHO binding K-i = 1.2 nM) were the most potent compounds of this series. Selectivity studies versus the other neurokinin receptors (hNK-8-CHO and hNK-1-CHO) revealed that 53 is about 100-fold selective for the hNK-3 versus hNK-2 receptor, with no affinity for the hNK-1 at concentrations up to 100 mu M. In vitro studies demonstrated that 53 is a potent functional antagonist of the hNK-3 receptor (reversal of senktide-induced contractions in rabbit isolated iris sphincter muscles and reversal of NKB-induced Ca2+ mobilization in CHO cells stably expressing the hNK-3 receptor), while in vivo this compound showed oral and intravenous activity in NK-3 receptor-driven models (senktide-induced behavioral responses in mice and senktide-induced miosis in rabbits). Overall, the biological data indicate that (S)-N-(1-phenylpropyl)-3-hydroxy-2-phenylquinoline-4-carboxamide (53, SE 223412) may serve as a pharmacological tool in animal models of disease to assess the functional and pathophysiological role of the NK-3 receptor and to establish therapeutic indications for non-peptide NK-3 receptor antagonists.

  DOI：

  10.1021/jm980633c
• 作为产物：
  描述：

  Boc-D-苯甘氨醇 在 TEA 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 (R)-tert-butyl (2-(1,3-dioxoisoindolin-2-yl)-1-phenylethyl)carbamate
  参考文献：
  名称：

  Discovery of a Novel Class of Selective Non-Peptide Antagonists for the Human Neurokinin-3 Receptor. 2. Identification of (S)-N-(1-Phenylpropyl)-3-hydroxy-2- phenylquinoline-4-carboxamide (SB 223412)

  摘要：

  Optimization of the previously reported 2-phenyl-4-quinolinecarboxamide NK-3 receptor antagonist 14, with regard to potential metabolic instability of the ester moiety and affinity and selectivity for the human neurokinin-3 (hNK-3) receptor, is described. The ester functionality could be successfully replaced by the ketone (31) or by lower alkyl groups (Et, 21, or n-Pr, 24). Investigation of the substitution pattern of the quinoline ring resulted in the identification of position 3 as a key position to enhance hNK-3 binding affinity and selectivity for the hNK-3 versus the hNK-2 receptor. All of the chemical groups introduced at this position, with the exception of halogens, increased the hNK-3 binding affinity, and compounds 53 (3-OH, SE 223412, hNK-3-CHO binding K-i = 1.4 nM) and 55 (3-NHz, hNK-3-CHO binding K-i = 1.2 nM) were the most potent compounds of this series. Selectivity studies versus the other neurokinin receptors (hNK-8-CHO and hNK-1-CHO) revealed that 53 is about 100-fold selective for the hNK-3 versus hNK-2 receptor, with no affinity for the hNK-1 at concentrations up to 100 mu M. In vitro studies demonstrated that 53 is a potent functional antagonist of the hNK-3 receptor (reversal of senktide-induced contractions in rabbit isolated iris sphincter muscles and reversal of NKB-induced Ca2+ mobilization in CHO cells stably expressing the hNK-3 receptor), while in vivo this compound showed oral and intravenous activity in NK-3 receptor-driven models (senktide-induced behavioral responses in mice and senktide-induced miosis in rabbits). Overall, the biological data indicate that (S)-N-(1-phenylpropyl)-3-hydroxy-2-phenylquinoline-4-carboxamide (53, SE 223412) may serve as a pharmacological tool in animal models of disease to assess the functional and pathophysiological role of the NK-3 receptor and to establish therapeutic indications for non-peptide NK-3 receptor antagonists.

  DOI：

  10.1021/jm980633c

文献信息

• SONIC HEDGEHOG MODULATORS
  申请人：Buhrlage Sara

  公开号：US20140094462A1

  公开（公告）日：2014-04-03

  Sonic Hedgehog modulators and methods of use thereof are provided for.

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  DOI：10.1002/chem.200501574

  日期：2006.9.6

  Application of new chiral ligands (R)-(-)-12 a and (S)-(+)-12 c (VALDY), derived from amino acids, to the title reaction, involving cinnamyl (linear) and isocinnamyl (branched) type substrates (4 and 5 --> 6), led to excellent regio- and enantioselectivities (>30:1, < or =98 % ee), showing that ligands with a single chiral center are capable of high asymmetric induction. The structural requirements

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  DOI：10.1016/j.bmc.2014.12.058

  日期：2015.2

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• Acid-Promoted Aza-Cyclization versus π-Cyclization of N-Acyliminium Species into Fused Pyrrolo[1,2-a]imidazolones and Pyrrolo[2,1-a]isoquinolinones
  作者：Adam Daïch、Jean-François Fleury、Pierre Netchitaïlo

  DOI：10.1055/s-0030-1260949

  日期：2011.8

  A new approach for the synthesis of fused imidazolones and isoquinolinones is presented. The key step of this sequence was the interception of an N-acyliminium species with nitrogen or π-aromatic nucleophiles under kinetic vs. thermodynamic control. In addition, in the presence of two π-aromatic nucleophiles, only the six-membered ring closure into pyrroloisoquinolinones occurred.

  本文介绍了一种合成融合咪唑酮和异喹啉酮的新方法。该序列的关键步骤是在动力学与热力学控制下，用氮或芳香族亲核物截取 N-酰亚胺物种。此外，在存在两个Ï-芳香族亲核物的情况下，只有六元环闭合成吡咯异喹啉酮。
• Chemokine receptor binding compounds
  申请人：Zhou Yuanxi

  公开号：US20070066624A1

  公开（公告）日：2007-03-22

  The present invention relates to chemokine receptor binding compounds, pharmaceutical compositions and their use. More specifically, the present invention relates to modulators of chemokine receptor activity, preferably modulators of CCR4 or CCR5. In one aspect, these compounds demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).

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