(4S)-1-苯甲酰基-4-{[(9H-芴-9-基甲氧基)羰基]氨基}-L-脯氨酸 | 204321-85-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: (4S)-1-苯甲酰基-4-{[(9H-芴-9-基甲氧基)羰基]氨基}-L-脯氨酸
• 中文别名: Fmoc-（2S，4S）-4-氨基-1-苯甲酰基-吡咯烷-2-羧酸
• 英文名称: (2S,4S)-1-benzoyl-4-N-(9-fluorenylmethoxycarbonyl)aminoproline
• 英文别名: Fmoc-(2S,4S)-4-amino-1-benzoyl-pyrrolidine-2-carboxylic acid；(2S,4S)-1-benzoyl-4-(9H-fluoren-9-ylmethoxycarbonylamino)pyrrolidine-2-carboxylic acid
• CAS: 204321-85-7
• 化学式: C₂₇H₂₄N₂O₅
• 分子量: 456.498
• InChiKey: YTWZZGPYBGALGM-UUOWRZLLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4S)-1-苯甲酰基-4-{[(9H-芴-9-基甲氧基)羰基]氨基}-L-脯氨酸 、 Fmoc-甘氨酸 、 Fmoc-L-天冬氨酸 beta-叔丁酯 、 NΑ-FMOC-NΩ-(2,2,5,7,8-五甲基苯并二氢吡喃-6-磺酰基)-L-精氨酸 生成 2-[[(2S)-2-[[(2S,4S)-4-[[(2S)-2-amino-4-[(2-methylpropan-2-yl)oxy]-4-oxobutanoyl]amino]-1-benzoylpyrrolidine-2-carbonyl]amino]-5-[[amino-[(2,2,5,7,8-pentamethyl-3,4-dihydrochromen-6-yl)sulfonylamino]methylidene]amino]pentanoyl]amino]acetic acid
  参考文献：
  名称：

  Discovery of Subnanomolar Arginine-Glycine-Aspartate-Based α_Vβ₃/α_Vβ₅ Integrin Binders Embedding 4-Aminoproline Residues

  摘要：

  The embodiment of 4-aminoproline residues (Amp) into the arginine-glycine-aspartate (RGD) sequence led to the discovery of a novel class of high-affinity alpha v beta(3)/alpha v beta(5) integrin binders [IC50h(alpha v beta(3)) 0.03-5.12 nM; IC50h(alpha v beta(5)) 0.88-154 nM]. A total of eight cyclopeptides of type cyclo-[-Arg-Gly-Asp-Amp-], 5-12, were assembled by a standard solid-phase peptide synthesis protocol that involved the C2-carboxyl and C4-amino functionalities of the proline scaffolds, leaving the N-alpha-nuclear site untouched. Functionalization of this vacant proline site with either alkyl or acyl substituents proved feasible, with significant benefit to the integrin binding capabilities of the ligands. Notably, six out of eight cyclopeptide inhibitors, 5-7 and 9-11, showed moderate yet significant selectivity toward the alpha v beta(3) receptor. The three-dimensional structure in water was determined by NMR techniques and molecular dynamics calculations. Docking studies to the X-ray crystal structure of the extracellular segment of integrin alpha v beta(3) complexed with reference compound 1 were also performed on selected analogues to highlight the structural features required for potent ligand binding affinity.

  DOI：

  10.1021/jm701214z
• 作为产物：
  描述：

  、 9-芴甲基-N-琥珀酰亚胺基碳酸酯 在 sodium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以425 mg的产率得到(4S)-1-苯甲酰基-4-{[(9H-芴-9-基甲氧基)羰基]氨基}-L-脯氨酸
  参考文献：
  名称：

  Discovery of Subnanomolar Arginine-Glycine-Aspartate-Based α_Vβ₃/α_Vβ₅ Integrin Binders Embedding 4-Aminoproline Residues

  摘要：

  The embodiment of 4-aminoproline residues (Amp) into the arginine-glycine-aspartate (RGD) sequence led to the discovery of a novel class of high-affinity alpha v beta(3)/alpha v beta(5) integrin binders [IC50h(alpha v beta(3)) 0.03-5.12 nM; IC50h(alpha v beta(5)) 0.88-154 nM]. A total of eight cyclopeptides of type cyclo-[-Arg-Gly-Asp-Amp-], 5-12, were assembled by a standard solid-phase peptide synthesis protocol that involved the C2-carboxyl and C4-amino functionalities of the proline scaffolds, leaving the N-alpha-nuclear site untouched. Functionalization of this vacant proline site with either alkyl or acyl substituents proved feasible, with significant benefit to the integrin binding capabilities of the ligands. Notably, six out of eight cyclopeptide inhibitors, 5-7 and 9-11, showed moderate yet significant selectivity toward the alpha v beta(3) receptor. The three-dimensional structure in water was determined by NMR techniques and molecular dynamics calculations. Docking studies to the X-ray crystal structure of the extracellular segment of integrin alpha v beta(3) complexed with reference compound 1 were also performed on selected analogues to highlight the structural features required for potent ligand binding affinity.

  DOI：

  10.1021/jm701214z

文献信息

• Integrin targeted cyclopeptide ligands, their preparation and use
  申请人：UNIVERSITA' DEGLI STUDI DI MILANO

  公开号：EP1961759A1

  公开（公告）日：2008-08-27

  The present invention relates to hybrid cyclopeptide compounds embodying pyrrolidine- or piperidine-based amino acid substructures grafted onto a RGD (-Arg-Gly-Asp-) tripeptide sequence and acting as targeting ligands towards integrin receptors, intended, for example, for the treatment of altered angiogenic phenomena or for the preparation of therapeutically and/or diagnostically useful compounds; the invention also concerns a process for the synthesis of said cyclopeptides and biologically active derivatives thereof.

  本发明涉及混合环肽化合物，该化合物体现了接枝到 RGD（-Arg-Gly-Asp-）三肽序列上的吡咯烷或哌啶基氨基酸亚结构，可作为整合素受体的靶向配体，用于治疗改变的血管生成现象或制备治疗和/或诊断有用的化合物；本发明还涉及合成所述环肽及其生物活性衍生物的工艺。
• INTEGRIN TARGETED CYCLOPEPTIDE LIGANDS, THEIR PREPARATION AND USE
  申请人：Casiraghi Giovanni

  公开号：US20100093612A1

  公开（公告）日：2010-04-15

  The present invention relates to novel hybrid cyclopeptide compounds embodying pyrrolidine- or piperidine-based amino acid substructures grafted onto a RGD (-Arg-Gly-Asp-) tripeptide sequence and acting as targeting ligands towards integrin receptors, intended, for example, for the treatment of altered angiogenic phenomena or for the preparation of therapeutically and/or diagnostically useful compounds; the invention also concerns a process for the synthesis of said cyclopeptides and biologically active derivatives thereof.
• Discovery of Subnanomolar Arginine-Glycine-Aspartate-Based α_Vβ₃/α_Vβ₅ Integrin Binders Embedding 4-Aminoproline Residues
  作者：Franca Zanardi、Paola Burreddu、Gloria Rassu、Luciana Auzzas、Lucia Battistini、Claudio Curti、Andrea Sartori、Giuseppe Nicastro、Gloria Menchi、Nicoletta Cini、Anna Bottonocetti、Silvia Raspanti、Giovanni Casiraghi

  DOI：10.1021/jm701214z

  日期：2008.3.1

  The embodiment of 4-aminoproline residues (Amp) into the arginine-glycine-aspartate (RGD) sequence led to the discovery of a novel class of high-affinity alpha v beta(3)/alpha v beta(5) integrin binders [IC50h(alpha v beta(3)) 0.03-5.12 nM; IC50h(alpha v beta(5)) 0.88-154 nM]. A total of eight cyclopeptides of type cyclo-[-Arg-Gly-Asp-Amp-], 5-12, were assembled by a standard solid-phase peptide synthesis protocol that involved the C2-carboxyl and C4-amino functionalities of the proline scaffolds, leaving the N-alpha-nuclear site untouched. Functionalization of this vacant proline site with either alkyl or acyl substituents proved feasible, with significant benefit to the integrin binding capabilities of the ligands. Notably, six out of eight cyclopeptide inhibitors, 5-7 and 9-11, showed moderate yet significant selectivity toward the alpha v beta(3) receptor. The three-dimensional structure in water was determined by NMR techniques and molecular dynamics calculations. Docking studies to the X-ray crystal structure of the extracellular segment of integrin alpha v beta(3) complexed with reference compound 1 were also performed on selected analogues to highlight the structural features required for potent ligand binding affinity.