(2R,4S)-1-(tert-butoxycarbonyl)-4-azidoproline benzyl ester | 1018332-19-8

• 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: (2R,4S)-1-(tert-butoxycarbonyl)-4-azidoproline benzyl ester
• 英文别名: 2-benzyl 1-tert-butyl (2R,4S)-4-azidopyrrolidine-1,2-dicarboxylate；2-O-benzyl 1-O-tert-butyl (2R,4S)-4-azidopyrrolidine-1,2-dicarboxylate
• CAS: 1018332-19-8
• 化学式: C₁₇H₂₂N₄O₄
• 分子量: 346.386
• InChiKey: NNBVAZYHYUBQCU-UONOGXRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  70.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2R,4S)-1-(tert-butoxycarbonyl)-4-azidoproline benzyl ester 在 劳森试剂 、 palladium 10% on activated carbon 、 氢气 、 碳酸氢钠 、 sodium carbonate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 二乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 94.34h， 生成 (4S)-1-methyl-N-{(3S,5R)-5-[4-(methylcarbamoyl)-1,3-thiazol-2-yl]pyrrolidin-3-yl}-2,6-dioxo-1,3-diazinane-4-carboxamide trifluoroacetate
  参考文献：
  名称：

  Characterization of Specific N-α-Acetyltransferase 50 (Naa50) Inhibitors Identified Using a DNA Encoded Library

  摘要：

  Two novel compounds were identified as Naa50 binders/inhibitors using DNA-encoded technology screening. Biophysical and biochemical data as well as cocrystal structures were obtained for both compounds (3a and 4a) to understand their mechanism of action. These data were also used to rationalize the binding affinity differences observed between the two compounds and a MLGP peptide-containing substrate. Cellular target engagement experiments further confirm the Naa50 binding of 4a and demonstrate its selectivity toward related enzymes (Naa10 and Naa60). Additional analogs of inhibitor 4a were also evaluated to study the binding mode observed in the cocrystal structures.

  DOI：

  10.1021/acsmedchemlett.0c00029
• 作为产物：
  描述：

  2-benzyl 1-tert-butyl (2R,4R)-4-hydroxypyrrolidine-1,2-dicarboxylate 在 二苯基膦叠氮化物 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 24.0h， 以96%的产率得到(2R,4S)-1-(tert-butoxycarbonyl)-4-azidoproline benzyl ester
  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

• 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.
• Characterization of Specific <i>N</i>-α-Acetyltransferase 50 (Naa50) Inhibitors Identified Using a DNA Encoded Library
  作者：Pei-Pei Kung、Patrick Bingham、Benjamin J. Burke、Qiuxia Chen、Xuemin Cheng、Ya-Li Deng、Dengfeng Dou、Junli Feng、Gary M. Gallego、Michael R. Gehring、Stephan K. Grant、Samantha Greasley、Anthony R. Harris、Karen A. Maegley、Jordan Meier、Xiaoyun Meng、Jose L. Montano、Barry A. Morgan、Brigitte S. Naughton、Prakash B. Palde、Thomas A. Paul、Paul Richardson、Sylvie Sakata、Alex Shaginian、William K. Sonnenburg、Chakrapani Subramanyam、Sergei Timofeevski、Jinqiao Wan、Wen Yan、Albert E. Stewart

  DOI：10.1021/acsmedchemlett.0c00029

  日期：2020.6.11

  Two novel compounds were identified as Naa50 binders/inhibitors using DNA-encoded technology screening. Biophysical and biochemical data as well as cocrystal structures were obtained for both compounds (3a and 4a) to understand their mechanism of action. These data were also used to rationalize the binding affinity differences observed between the two compounds and a MLGP peptide-containing substrate. Cellular target engagement experiments further confirm the Naa50 binding of 4a and demonstrate its selectivity toward related enzymes (Naa10 and Naa60). Additional analogs of inhibitor 4a were also evaluated to study the binding mode observed in the cocrystal structures.