5-[(Diphenyl-p-tolyl-methyl)-amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)-pentanoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 5-[(Diphenyl-p-tolyl-methyl)-amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)-pentanoic acid
• 英文别名: N-Fmoc-N5-(4-methyltrityl)-D-ornithine；2-(9H-fluoren-9-ylmethoxycarbonylamino)-5-[[(4-methylphenyl)-diphenylmethyl]amino]pentanoic acid
• 化学式: C₄₀H₃₈N₂O₄
• 分子量: 610.753
• InChiKey: RRYSGISHZIBOJC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  46
• 可旋转键数：
  13
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-carbamoyl-1-(2,4-dinitrophenyl)pyridinium chloride 、 L-焦谷氨酸 、 5-[(Diphenyl-p-tolyl-methyl)-amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)-pentanoic acid 、 alkaline earth salt of/the/ methylsulfuric acid 生成 Trifluoro-acetate3-carbamoyl-1-{5-(2-carbamoyl-pyrrolidin-1-yl)-5-oxo-4-[(5-oxo-pyrrolidine-2-carbonyl)-amino]-pentyl}-pyridinium;
  参考文献：
  名称：

  Centrally Acting and Metabolically Stable Thyrotropin-Releasing Hormone Analogues by Replacement of Histidine with Substituted Pyridinium

  摘要：

  Metabolically stable and centrally acting thyrotropin-releasing hormone (TRH) analogues were designed by replacing the central histidine with substituted pyridinium moieties. Their analeptic and acetylcholine-releasing actions were evaluated to assess their potency as central nervous system (CNS) agents. A strong experimental connection between these two CNS-mediated actions of the TRH analogues was obtained in subject animals. The analogue 3-(aminocarbonyl)-1-(3-[2-(aminocarbonyl)pyrrolidin-1-yl]-3-oxo-2-{[(5-oxopyrrolidin-2-yl)carbonyl]amino}propyl)-pyridinium (1a) showed the highest (TRH-equivalent) potency and longest, dose-dependent duration of action from a series of homologous compounds in antagonizing pentobarbital-induced narcosis when administered intravenously in its CNS-permeable prodrug form (2a) obtained via reduction of the pyridinium moiety to the nonionic dihydropyridine. The maximum change in hippocampal acetylcholine concentration upon perfusion of the pyridinium-containing tripeptides into the hippocampus of rats was also achieved with la. No binding to the endocrine TRH receptor was measured for the TRH analogues reported here; therefore, our design afforded a novel lead for centrally acting TRH analogues. We have also demonstrated the benefits of the prodrug approach on the pharmacokinetics and brain uptake/retention of pyridinium-containing TRH analogues (measured by in vivo microdialysis sampling) upon systemic administration.

  DOI：

  10.1021/jm020531t

文献信息

• [EN] DNA-TEMPLATED MACROCYCLE LIBRARY<br/>[FR] BIBLIOTHÈQUE DE MACROCYCLES À MATRICE D'ADN
  申请人：HARVARD COLLEGE

  公开号：WO2019168654A9

  公开（公告）日：2019-10-17
• STRUCTURE-BASED PEPTIDE INHIBITORS OF P53 AGGREGATION AS A NEW APPROACH TO CANCER THERAPEUTICS
  申请人：The Regents of the University of California

  公开号：EP2994476B1

  公开（公告）日：2019-07-31
• DNA-TEMPLATED MACROCYCLE LIBRARY
  申请人：President and Fellows of Harvard Co

  公开号：US20200399634A1

  公开（公告）日：2020-12-24

  The present invention provides nucleic acid templates (e.g., including orthogonal codon sets (e.g., codons from orthogonal codon sets depicted in Tables 5 or 7)) for DNA-templated methods of synthesizing, selecting, and amplifying compounds (e.g., polymers and/or small molecules) described herein. Also provided are novel macrocyclic compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, libraries, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing a disease (e.g., a disease associated with aberrant enzyme activity (e.g., aberrant protease and/or kinase activity (e.g., aberrant IDE activity)), impaired insulin signaling, or insulin resistance in a subject (e.g., a subject having diabetes). Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit aberrant protease activity (e.g., aberrant IDE activity).