氨基(9H-芴-9-基)乙酸 | 155172-78-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: 氨基(9H-芴-9-基)乙酸
• 英文名称: L-2-(9-fluorenyl)glycine
• 英文别名: 2-(9-Fluorenyl)glycine；(2S)-2-amino-2-(9H-fluoren-9-yl)acetic acid
• CAS: 155172-78-4
• 化学式: C₁₅H₁₃NO₂
• 分子量: 239.274
• InChiKey: NYYSELKAMGOUDG-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  9-溴芴 在 盐酸 、 六甲基磷酰三胺 、 lithium hydroxide 、 正丁基锂 、 silica gel 作用下， 以 四氢呋喃 、 氯仿 、 水 为溶剂， 反应 5.0h， 生成 氨基(9H-芴-9-基)乙酸
  参考文献：
  名称：

  Design and Synthesis of Side-Chain Conformationally Restricted Phenylalanines and Their Use for Structure-Activity Studies on Tachykinin NK-1 Receptor

  摘要：

  Constrained analogues of phenylalanine have been conceptually designed for analyzing the binding pockets of Phe(7) (S-7) and Phe(8) (S-8), two aromatic residues important for the pharmacological properties of SP, i.e., L-tetrahydroisoquinoleic acid, L-diphenylalanine, L-9-fluorenylglycine (Flg), 2-indanylglycine, the diastereomers of L-1-indanylglycine (Ing) and L-1-benz[f]indanylglycine (Bfi), and the Z and E isomers of dehydrophenylalanine (Delta(z)Phe, Delta(E)Phe). Binding studies were performed with appropriate ligands and tissue preparations allowing the discrimination of the three tachykinin binding sites, NK-1, NK-2, and NK-3. The potencies of these agonists were evaluated in the guinea pig ileum bioassay. According to the binding data, we can conclude that the S-7 subsite is small, only the gauche (-) probe [(2S,3S)-Ing(7)]SP presents a high affinity for specific NK-1 binding sites. Surprisingly, the [Delta(E)Phe(7)]SP analogue, which projects the aromatic ring toward the trans orientation, is over 40-fold more potent than the Z isomer, [Delta(Z)Phe(7)]SP. A plausible explanation of these conflictual results Is that either the binding protein quenches the minor trans rotamer of [(2S,3S)-Ing(7)]SP in solution or this constrained amino acid side chain rotates when inserted in the protein. In position 8, the high binding affinities of [Flg(8)]SP and [(2S,3S)-Bfi(8)]SP suggest that the S-8 subsite is large enough to accept two aromatic rings in the gauche (-) and one aromatic ring in the trans direction. Peptides bearing two conformational probes in positions 7, 8, or 9 led to postulate that S-7, S-8, and S-9 subsites are independent from each other. The volumes available for side chains 7 and 8 can be estimated to be close to 110 and 240 Angstrom(3), respectively. The large volume of the S-8 subsite raises question on the localization of the SP-binding site in the NK-1 receptor. If SP were to bind in the transmembrane domains, the cleft defined by the seven transmembrane segments must rearrange during the binding process in order to bind a peptide in an ac-helical structure and at least one large binding subsite in position 8. Thus, indirect topographical analysis with constrained amino acids might contribute to the analysis of the receptor/ligand dynamics. Finally, this study demonstrates that a good knowledge of the peptidic backbone structure and a combination of constrained amino acids are prerequisites to confidently attribute the preferred orientation(s) of an amino acid side chain.

  DOI：

  10.1021/jm00037a009

文献信息

• THROMBIN INHIBITORS
  申请人：TRIGEN LIMITED

  公开号：EP0910583A1

  公开（公告）日：1999-04-28
• US6127340A
  申请人：——

  公开号：US6127340A

  公开（公告）日：2000-10-03
• [EN] THROMBIN INHIBITORS<br/>[FR] INHIBITEURS DE THROMBINE
  申请人：TRIGEN LIMITED

  公开号：WO1998000443A1

  公开（公告）日：1998-01-08

  (EN) Bifunctional peptide thrombin inhibitors and methods of their manufacture are provided. The inhibitors have an anion-binding exosite associating moiety joined to a catalytic site directed moiety. A spacer peptide and a non-peptide linker moiety enable both the anion-binding exosite associating moiety and the catalytic site directed moiety to bind simultaneously to a thrombin molecule thereby permitting the treatment of thrombosis.(FR) L'invention concerne des inhibiteurs peptidiques bifonctionnels de thrombine et leurs procédés de fabrication. Ces inhibiteurs possèdent une fraction d'association à l'exosite de fixation d'anions reliée à une fraction dirigée catalytique. Un peptide espaceur et une fraction de séquence de liaison non peptidique permettent à la fois à la fraction d'association à l'exosite de fixation d'anions et à la fraction dirigée catalytique de se lier simultanément à une molécule de thrombine, facilitant ainsi le traitement de la thrombose.
• Design and Synthesis of Side-Chain Conformationally Restricted Phenylalanines and Their Use for Structure-Activity Studies on Tachykinin NK-1 Receptor
  作者：Hubert Josien、Solange Lavielle、Alie Brunissen、Monique Saffroy、Yvette Torrens、Jean-Claude Beaujouan、Jacques Glowinski、Gerard Chassaing

  DOI：10.1021/jm00037a009

  日期：1994.5

  Constrained analogues of phenylalanine have been conceptually designed for analyzing the binding pockets of Phe(7) (S-7) and Phe(8) (S-8), two aromatic residues important for the pharmacological properties of SP, i.e., L-tetrahydroisoquinoleic acid, L-diphenylalanine, L-9-fluorenylglycine (Flg), 2-indanylglycine, the diastereomers of L-1-indanylglycine (Ing) and L-1-benz[f]indanylglycine (Bfi), and the Z and E isomers of dehydrophenylalanine (Delta(z)Phe, Delta(E)Phe). Binding studies were performed with appropriate ligands and tissue preparations allowing the discrimination of the three tachykinin binding sites, NK-1, NK-2, and NK-3. The potencies of these agonists were evaluated in the guinea pig ileum bioassay. According to the binding data, we can conclude that the S-7 subsite is small, only the gauche (-) probe [(2S,3S)-Ing(7)]SP presents a high affinity for specific NK-1 binding sites. Surprisingly, the [Delta(E)Phe(7)]SP analogue, which projects the aromatic ring toward the trans orientation, is over 40-fold more potent than the Z isomer, [Delta(Z)Phe(7)]SP. A plausible explanation of these conflictual results Is that either the binding protein quenches the minor trans rotamer of [(2S,3S)-Ing(7)]SP in solution or this constrained amino acid side chain rotates when inserted in the protein. In position 8, the high binding affinities of [Flg(8)]SP and [(2S,3S)-Bfi(8)]SP suggest that the S-8 subsite is large enough to accept two aromatic rings in the gauche (-) and one aromatic ring in the trans direction. Peptides bearing two conformational probes in positions 7, 8, or 9 led to postulate that S-7, S-8, and S-9 subsites are independent from each other. The volumes available for side chains 7 and 8 can be estimated to be close to 110 and 240 Angstrom(3), respectively. The large volume of the S-8 subsite raises question on the localization of the SP-binding site in the NK-1 receptor. If SP were to bind in the transmembrane domains, the cleft defined by the seven transmembrane segments must rearrange during the binding process in order to bind a peptide in an ac-helical structure and at least one large binding subsite in position 8. Thus, indirect topographical analysis with constrained amino acids might contribute to the analysis of the receptor/ligand dynamics. Finally, this study demonstrates that a good knowledge of the peptidic backbone structure and a combination of constrained amino acids are prerequisites to confidently attribute the preferred orientation(s) of an amino acid side chain.