ethyl (2S)-3-(3-bromophenyl)-2-(tertbutoxycarbonylamino)propanoate | 1159502-91-6

• 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: ethyl (2S)-3-(3-bromophenyl)-2-(tertbutoxycarbonylamino)propanoate
• 英文别名: (S)-3-(3-bromophenyl)-2-tert-butoxycarbonylaminopropionic acid ethyl ester；N-Boc-3-bromo-L-phenylalanine ethyl ester；ethyl (2S)-3-(3-bromophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• CAS: 1159502-91-6
• 化学式: C₁₆H₂₂BrNO₄
• mdl: MFCD28505103
• 分子量: 372.259
• InChiKey: ZTVUZOMRSCWUOP-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl (2S)-3-(3-bromophenyl)-2-(tertbutoxycarbonylamino)propanoate 在 bis-triphenylphosphine-palladium(II) chloride 、 水 、 氢溴酸 作用下， 以 乙二醇二甲醚 为溶剂， 反应 2.25h， 生成 (S)-3'-(2-amino-2-carboxyethyl)biphenyl-3-carboxylic acid
  参考文献：
  名称：

  3-Substituted phenylalanines as selective AMPA- and kainate receptor ligands

  摘要：

  On the basis of X-ray structures of ionotropic glutamate receptor constructs in complex with amino acid-based AMPA and kainate receptor antagonists, a series of rigid as well as flexible biaromatic alanine derivatives carrying selected hydrogen bond acceptors and donors have been synthesized in order to investigate the structural determinants for receptor selectivity between AMPA and the GluR5 subtype of kainate receptors. Compounds selective for either GluR5 or AMPA receptors were identified. One particular substituent position appeared to be of special importance for control of ligand selectivity. Using molecular modeling the observed structure-activity relationships at AMPA and GluR5 receptors were deduced. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.07.021
• 作为产物：
  描述：

  Boc-L-3-溴苯丙氨酸 、 碘乙烷 在 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以89%的产率得到ethyl (2S)-3-(3-bromophenyl)-2-(tertbutoxycarbonylamino)propanoate
  参考文献：
  名称：

  3-Substituted phenylalanines as selective AMPA- and kainate receptor ligands

  摘要：

  On the basis of X-ray structures of ionotropic glutamate receptor constructs in complex with amino acid-based AMPA and kainate receptor antagonists, a series of rigid as well as flexible biaromatic alanine derivatives carrying selected hydrogen bond acceptors and donors have been synthesized in order to investigate the structural determinants for receptor selectivity between AMPA and the GluR5 subtype of kainate receptors. Compounds selective for either GluR5 or AMPA receptors were identified. One particular substituent position appeared to be of special importance for control of ligand selectivity. Using molecular modeling the observed structure-activity relationships at AMPA and GluR5 receptors were deduced. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.07.021

文献信息

• [EN] PHOSPHONIC ACID DERIVATES AND THEIR USE AS P2Y12 RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS D'ACIDE PHOSPHONIQUE ET LEUR UTILISATION EN TANT QU'ANTAGONISTES DU RÉCEPTEUR P2Y12
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2009069100A1

  公开（公告）日：2009-06-04

  The invention relates to 2-phenyl-pyrimidine derivatives containing a phosphonic acid motif and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals. (I).

  这项发明涉及含有膦酸基团的2-苯基嘧啶衍生物，以及它们作为P2Y12受体拮抗剂在治疗和/或预防外周血管、内脏-、肝脏和肾脏血管、心血管和脑血管疾病或与血小板聚集有关的疾病或状况中的使用，包括人类和其他哺乳动物中的血栓形成。（I）。
• PHOSPHONIC ACID DERIVATES AD THEIR USE AS P2Y12 RECEPTOR ANTAGONISTS
  申请人：Caroff Eva

  公开号：US20100261678A1

  公开（公告）日：2010-10-14

  The invention relates to 2-phenyl-pyrimidine derivatives containing a phosphonic acid motif and their use as P2Y 12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals. (I).

  本发明涉及含有膦酸基团的2-苯基嘧啶衍生物及其作为P2Y12受体拮抗剂在治疗和/或预防外周血管、内脏、肝脏和肾脏血管、心血管和脑血管疾病或与血小板聚集有关的病症，包括人类和其他哺乳动物的血栓形成中的应用。(I)。
• US8518912B2
  申请人：——

  公开号：US8518912B2

  公开（公告）日：2013-08-27
• 3-Substituted phenylalanines as selective AMPA- and kainate receptor ligands
  作者：Ewa Szymańska、Darryl S. Pickering、Birgitte Nielsen、Tommy N. Johansen

  DOI：10.1016/j.bmc.2009.07.021

  日期：2009.9.1

  On the basis of X-ray structures of ionotropic glutamate receptor constructs in complex with amino acid-based AMPA and kainate receptor antagonists, a series of rigid as well as flexible biaromatic alanine derivatives carrying selected hydrogen bond acceptors and donors have been synthesized in order to investigate the structural determinants for receptor selectivity between AMPA and the GluR5 subtype of kainate receptors. Compounds selective for either GluR5 or AMPA receptors were identified. One particular substituent position appeared to be of special importance for control of ligand selectivity. Using molecular modeling the observed structure-activity relationships at AMPA and GluR5 receptors were deduced. (C) 2009 Elsevier Ltd. All rights reserved.
• Studies on Aryl-Substituted Phenylalanines: Synthesis, Activity, and Different Binding Modes at AMPA Receptors
  作者：Ewa Szymanska、Karla Frydenvang、Darryl S. Pickering、Christian Krintel、Birgitte Nielsen、Ayesheh Kooshki、Linda G. Zachariassen、Lars Olsen、Jette S. Kastrup、Tommy N. Johansen

  DOI：10.1021/acs.jmedchem.5b01666

  日期：2016.1.14

  A series of racemic aryl-substituted phenylalanines was synthesized and evaluated in vitro at recombinant rat GluA1-3, at GluK1-3, and at native AMPA receptors. The individual enantiomers of two target compounds, (RS)-2-amino-3-(3,4-dichloro-5-(5-hydroxypyridin-3-yl)phenyl)propanoic acid 37 and (RS)-2-amino-3-(3'-hydroxybiphenyl-3-yl)propanoic acid 38, were characterized. (S)-37 and (R)-38 were identified as the only biologically active isomers, both being antagonists at GluA2 receptors with K-b of 1.80 and 3.90 mu M, respectively. To address this difference in enantiopharmacology, not previously seen for amino acid-based AMPA receptor antagonists, X-ray crystal structures of both eutomers in complex with the GluA2 ligand binding domain were solved. The cocrystal structures of (S)-37 and (R)-38 showed similar interactions of the amino acid parts but unexpected and different orientations and interactions of the biaromatic parts of the ligands inside the binding site, with (R)-38 having a binding mode not previously identified for amino acid-based antagonists.