(2S)-2-([(9H-芴-9-基甲氧基)羰基]氨基)-3-(喹啉-3-基)丙酸 | 281655-61-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: (2S)-2-([(9H-芴-9-基甲氧基)羰基]氨基)-3-(喹啉-3-基)丙酸
• 英文名称: N-{[(9H-fluoren-9-yl)methoxy]carbonyl}-3-quinolin-3-yl-L-alanine
• 英文别名: N-Fmoc-L-3-(3-quinolyl)alanine；Fmoc-3-(3'-quinolyl)-L-alanine；(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-quinolin-3-ylpropanoic acid
• CAS: 281655-61-6
• 化学式: C₂₇H₂₂N₂O₄
• mdl: MFCD01632017
• 分子量: 438.483
• InChiKey: HZZZBOUYIXBVNP-VWLOTQADSA-N

物化性质

• 熔点：
  146-148 °C
• 沸点：
  697.5±55.0 °C(Predicted)
• 密度：
  1.325±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.148
• 拓扑面积：
  88.5
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  (S)-di-tert-butyl 2-(3-((S)-6-amino-1-(tert-butoxy)-1-oxohexan-2-yl)ureido)pentanedioate 、 (2S)-2-([(9H-芴-9-基甲氧基)羰基]氨基)-3-(喹啉-3-基)丙酸 在 N-甲基吗啉 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以27%的产率得到tri-tert-butyl (5S,12S,16S)-1-(9H-fluoren-9-yl)-3,6,14-trioxo-5-[(quinolin-3-yl)methyl]-2-oxa-4,7,13,15-tetraazaoctadecane-12,16,18-tricarboxylate
  参考文献：
  名称：

  [EN] TARGETED RADIOPHARMACEUTICALS FOR THE DIAGNOSIS AND TREATMENT OF PROSTATE CANCER
  [FR] PRODUITS RADIOPHARMACEUTIQUES CIBLÉS POUR LE DIAGNOSTIC ET LE TRAITEMENT DU CANCER DE LA PROSTATE

  摘要：

  通用式(I)的化合物：其中：n为1、2或3；R1、R2、R3和R4独立地代表OH或Q；Q代表从群组中选择的组织靶向基团，或其立体异构体、水合物、溶剂合物、盐或其混合物，制备所述化合物的方法，用于制备所述化合物的中间化合物，包含所述化合物的药物组合物和组合物，以及用于制造用于治疗或预防疾病的药物组合物的所述化合物的用途，特别是软组织疾病的治疗或预防，作为唯一药剂或与其他活性成分结合使用。

  公开号：

  WO2021013978A1
• 作为产物：
  描述：

  3-喹啉甲醛 在 盐酸 、 (R)-[Rh(COD)(MaxPHOS)]BF₄ 、 氢气 、 sodium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 为溶剂， 100.0 ℃ 、1.5 MPa 条件下， 反应 81.5h， 生成 (2S)-2-([(9H-芴-9-基甲氧基)羰基]氨基)-3-(喹啉-3-基)丙酸
  参考文献：
  名称：

  SSTR1- and SSTR3-Selective Somatostatin Analogues

  摘要：

  AbstractWe prepared the two enantiomers of 3‐(3′‐quinolyl)‐alanine (Qla, 1) in multigram scale by asymmetric hydrogenation. These amino acids, protected as Fmoc derivatives, were then used in the solid‐phase synthesis of two new somatostatin 14 (SRIF‐14) analogues 8 a and 8 b, tetradecapeptides in which the tryptophan residue (Trp8) is replaced by one of the two enantiomers of 3‐(3′‐quinolyl)‐alanine (Qla8) and therefore lack the NH bond in residue 8. The selectivity of these new analogues for the somatostatin receptors, SSTR1–5, was measured. Substitution with L‐Qla8 yielded peptide 8 a, which was highly selective for SSTR1 and SSTR3, with an affinity similar to that of SRIF‐14. Substitution by D‐Qla gave the relatively selective analogue 8 b, which showed high affinity for SSTR3 and significant affinity for SSTR1, SSTR2 and SSTR5. The biological results demonstrate that bulky and electronically poor aromatic amino acids at position 8 are compatible with strong activity with SSTR1 and SSTR3. Remarkably, these high affinity levels were achieved with peptides in which the conformational mobility was increased with respect to that of SRIF‐14. This observation suggests that conformational rigidity is not required, and might be detrimental to the interaction with receptors SSTR1 and SSTR3. The absence of an indole N proton in Qla8 might also contribute to the increased flexibility observed in these analogues.

  DOI：

  10.1002/cbic.201000597

文献信息

• Growth Hormone Secretagogue Receptor 1A Ligands
  申请人：Schambye Hans T.

  公开号：US20080300180A1

  公开（公告）日：2008-12-04

  The present invention relates to new growth hormone secretagogue receptor 1A (GHS-R 1A) ligands, and pharmaceutical compositions comprising any of the new GHS-R1 A ligands. The ligands are suitable for a wide range of applications, and thus the present invention also relates to use of the GHS-R1 A ligands according to the present invention in the manufacture of a medicament for the treatment of an individual in need thereof. In another aspect, the present invention relates to a method of treatment of an individual in need thereof, comprising administering to said individual one or more of the GHS-R1A ligands disclosed herein, such as e.g. for treatment of cancer cachexia.

  本发明涉及新型生长激素促分泌素受体1A（GHS-R 1A）配体，以及包含任何此类新型GHS-R1A配体的药物组合物。这些配体适用于广泛的应用范围，因此本发明还涉及根据本发明的GHS-R1A配体在制造用于治疗有此需要的个体的药物中的用途。在另一方面，本发明涉及一种治疗有此需要的个体的方法，包括向该个体施用本文披露的一种或多种GHS-R1A配体，例如用于治疗癌症恶病质。
• [EN] ACRYLAMIDE DERIVATIVES AS VLA-1 INTEGRIN ANTAGONISTS AND USES THEREOF<br/>[FR] DERIVES D'ACRYLAMIDE SERVANT D'ANTAGONISTES DE L'INTEGRINE VLA-1, ET LEURS UTILISATIONS
  申请人：ICOS CORP

  公开号：WO2005016883A2

  公开（公告）日：2005-02-24

  Compounds that are VLA-1 integrin antagonists are disclosed. Also disclosed are compositions containing such compounds, and methods of using such compounds in treating diseases mediated, at least in part, by the VLA-1 integrin.
• [EN] TARGETED RADIOPHARMACEUTICALS FOR THE DIAGNOSIS AND TREATMENT OF PROSTATE CANCER<br/>[FR] PRODUITS RADIOPHARMACEUTIQUES CIBLÉS POUR LE DIAGNOSTIC ET LE TRAITEMENT DU CANCER DE LA PROSTATE
  申请人：BAYER AS

  公开号：WO2021013978A1

  公开（公告）日：2021-01-28

  A compound of general formula (I): wherein: n is 1, 2 or 3; R1, R2, R3 and R4, independently represent OH or Q; and 20 Q represents a tissue-targeting moeity selected from the group consisting of or a stereoisomer, a hydrate, a solvate, or a salt thereof, or a mixture of same, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said 25 compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of soft tissue diseases, as a sole agent or in combination with other active ingredients.

  通用式(I)的化合物：其中：n为1、2或3；R1、R2、R3和R4独立地代表OH或Q；Q代表从群组中选择的组织靶向基团，或其立体异构体、水合物、溶剂合物、盐或其混合物，制备所述化合物的方法，用于制备所述化合物的中间化合物，包含所述化合物的药物组合物和组合物，以及用于制造用于治疗或预防疾病的药物组合物的所述化合物的用途，特别是软组织疾病的治疗或预防，作为唯一药剂或与其他活性成分结合使用。
• SSTR1- and SSTR3-Selective Somatostatin Analogues
  作者：Rosario Ramón、Pablo Martín-Gago、Xavier Verdaguer、Maria J. Macias、Pau Martin-Malpartida、Jimena Fernández-Carneado、Marc Gomez-Caminals、Berta Ponsati、Pilar López-Ruiz、Maria Alicia Cortés、Begoña Colás、Antoni Riera

  DOI：10.1002/cbic.201000597

  日期：2011.3.7

  AbstractWe prepared the two enantiomers of 3‐(3′‐quinolyl)‐alanine (Qla, 1) in multigram scale by asymmetric hydrogenation. These amino acids, protected as Fmoc derivatives, were then used in the solid‐phase synthesis of two new somatostatin 14 (SRIF‐14) analogues 8 a and 8 b, tetradecapeptides in which the tryptophan residue (Trp8) is replaced by one of the two enantiomers of 3‐(3′‐quinolyl)‐alanine (Qla8) and therefore lack the NH bond in residue 8. The selectivity of these new analogues for the somatostatin receptors, SSTR1–5, was measured. Substitution with L‐Qla8 yielded peptide 8 a, which was highly selective for SSTR1 and SSTR3, with an affinity similar to that of SRIF‐14. Substitution by D‐Qla gave the relatively selective analogue 8 b, which showed high affinity for SSTR3 and significant affinity for SSTR1, SSTR2 and SSTR5. The biological results demonstrate that bulky and electronically poor aromatic amino acids at position 8 are compatible with strong activity with SSTR1 and SSTR3. Remarkably, these high affinity levels were achieved with peptides in which the conformational mobility was increased with respect to that of SRIF‐14. This observation suggests that conformational rigidity is not required, and might be detrimental to the interaction with receptors SSTR1 and SSTR3. The absence of an indole N proton in Qla8 might also contribute to the increased flexibility observed in these analogues.