benzyl N-[(2S)-1-[[(2S)-5-[[amino-[(4-methoxy-2,3,6-trimethylphenyl)sulfonylamino]methylidene]amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)pentanoyl]amino]-3-phenylpropan-2-yl]carbamate | 1202508-82-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: benzyl N-[(2S)-1-[[(2S)-5-[[amino-[(4-methoxy-2,3,6-trimethylphenyl)sulfonylamino]methylidene]amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)pentanoyl]amino]-3-phenylpropan-2-yl]carbamate
• CAS: 1202508-82-4
• 化学式: C₄₈H₅₄N₆O₈S
• 分子量: 875.058
• InChiKey: JTISRKYBXFCUDH-MVNOZWHVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  63
• 可旋转键数：
  21
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  208
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  benzyl N-[(2S)-1-[[(2S)-5-[[amino-[(4-methoxy-2,3,6-trimethylphenyl)sulfonylamino]methylidene]amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)pentanoyl]amino]-3-phenylpropan-2-yl]carbamate 在 二甲胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 benzyl N-[(2S)-1-[[(2S)-2-amino-5-[[amino-[(4-methoxy-2,3,6-trimethylphenyl)sulfonylamino]methylidene]amino]pentanoyl]amino]-3-phenylpropan-2-yl]carbamate
  参考文献：
  名称：

  Antiangiogenic Effect of Dual/Selective α₅β₁/α_vβ₃ Integrin Antagonists Designed on Partially Modified Retro-Inverso Cyclotetrapeptide Mimetics

  摘要：

  Recent evidence highlighted the role of alpha(5)beta(1) integrin in angiogenesis and In regulating alpha(v)beta(3) integrin function. As a consequence, selective alpha(5)beta(1) integrin inhibitors or dual alpha(5)beta(1)/alpha(v)beta(3) integrin inhibitors are considered promising candidates for the development of cancer therapeutic agents. In this paper, we describe the synthesis and pharmacological characterization of a minilibrary of cyclotetrapeptide mimetics containing a PMRI Arg-Gly-Asp sequence. In particular, c[(R)-beta Phe psi(NHCO)Asp psi-(NHCO)Gly-Arg] (3) displayed a good activity in inhibiting the alpha(v)beta(3) integrin-mediated cell adhesion of fibronectin or vitronectin, its well as the adhesion of fibronectin to the alpha(5)beta(1) integrin. Interestingly, the diastereomeric compound c[(S)- beta Phe psi(NHCO)Asp psi(NHCO)Gly-Arg] (2) maintained a good efficacy in inhibiting alpha(5)beta(1) integrin while gaining a certain selectivity over alpha(v)beta(3) integrin. These two integrin antagonists significantly inhibited bFGF-induced human endothelial cell tube formation at submicromolar concentrations. Conformational analysis and Molecular Docking calculations Suggest that the different alpha(5)beta(1) versus alpha(v)beta(3) selectivity of 2 and 3 can be rationalized on the basis of the alternative display of the aromatic side chain adjacent to Asp.

  DOI：

  10.1021/jm9013532
• 作为产物：
  描述：

  N-Fmoc-N'-(4-甲氧基-2,3,6-三甲基苯磺酰基)-L-精氨酸 、 [(S)-1-(氨甲基)-2-苯基乙基]-甲酸苄酯 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.17h， 生成 benzyl N-[(2S)-1-[[(2S)-5-[[amino-[(4-methoxy-2,3,6-trimethylphenyl)sulfonylamino]methylidene]amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)pentanoyl]amino]-3-phenylpropan-2-yl]carbamate
  参考文献：
  名称：

  Antiangiogenic Effect of Dual/Selective α₅β₁/α_vβ₃ Integrin Antagonists Designed on Partially Modified Retro-Inverso Cyclotetrapeptide Mimetics

  摘要：

  Recent evidence highlighted the role of alpha(5)beta(1) integrin in angiogenesis and In regulating alpha(v)beta(3) integrin function. As a consequence, selective alpha(5)beta(1) integrin inhibitors or dual alpha(5)beta(1)/alpha(v)beta(3) integrin inhibitors are considered promising candidates for the development of cancer therapeutic agents. In this paper, we describe the synthesis and pharmacological characterization of a minilibrary of cyclotetrapeptide mimetics containing a PMRI Arg-Gly-Asp sequence. In particular, c[(R)-beta Phe psi(NHCO)Asp psi-(NHCO)Gly-Arg] (3) displayed a good activity in inhibiting the alpha(v)beta(3) integrin-mediated cell adhesion of fibronectin or vitronectin, its well as the adhesion of fibronectin to the alpha(5)beta(1) integrin. Interestingly, the diastereomeric compound c[(S)- beta Phe psi(NHCO)Asp psi(NHCO)Gly-Arg] (2) maintained a good efficacy in inhibiting alpha(5)beta(1) integrin while gaining a certain selectivity over alpha(v)beta(3) integrin. These two integrin antagonists significantly inhibited bFGF-induced human endothelial cell tube formation at submicromolar concentrations. Conformational analysis and Molecular Docking calculations Suggest that the different alpha(5)beta(1) versus alpha(v)beta(3) selectivity of 2 and 3 can be rationalized on the basis of the alternative display of the aromatic side chain adjacent to Asp.

  DOI：

  10.1021/jm9013532

文献信息

• Antiangiogenic Effect of Dual/Selective α₅β₁/α_vβ₃ Integrin Antagonists Designed on Partially Modified Retro-Inverso Cyclotetrapeptide Mimetics
  作者：Luca Gentilucci、Giuliana Cardillo、Santi Spampinato、Alessandra Tolomelli、Federico Squassabia、Rossella De Marco、Andrea Bedini、Monica Baiula、Laura Belvisi、Monica Civera

  DOI：10.1021/jm9013532

  日期：2010.1.14

  Recent evidence highlighted the role of alpha(5)beta(1) integrin in angiogenesis and In regulating alpha(v)beta(3) integrin function. As a consequence, selective alpha(5)beta(1) integrin inhibitors or dual alpha(5)beta(1)/alpha(v)beta(3) integrin inhibitors are considered promising candidates for the development of cancer therapeutic agents. In this paper, we describe the synthesis and pharmacological characterization of a minilibrary of cyclotetrapeptide mimetics containing a PMRI Arg-Gly-Asp sequence. In particular, c[(R)-beta Phe psi(NHCO)Asp psi-(NHCO)Gly-Arg] (3) displayed a good activity in inhibiting the alpha(v)beta(3) integrin-mediated cell adhesion of fibronectin or vitronectin, its well as the adhesion of fibronectin to the alpha(5)beta(1) integrin. Interestingly, the diastereomeric compound c[(S)- beta Phe psi(NHCO)Asp psi(NHCO)Gly-Arg] (2) maintained a good efficacy in inhibiting alpha(5)beta(1) integrin while gaining a certain selectivity over alpha(v)beta(3) integrin. These two integrin antagonists significantly inhibited bFGF-induced human endothelial cell tube formation at submicromolar concentrations. Conformational analysis and Molecular Docking calculations Suggest that the different alpha(5)beta(1) versus alpha(v)beta(3) selectivity of 2 and 3 can be rationalized on the basis of the alternative display of the aromatic side chain adjacent to Asp.