2,4,6-三甲基苯丙氨酸 | 146277-47-6

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 苯丙氨酸类衍生物
• 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
• 中文名称: 2,4,6-三甲基苯丙氨酸
• 中文别名: 2,4,6-三甲基-L-苯丙氨酸
• 英文名称: 2',4',6'-trimethyl-L-phenylalanine
• 英文别名: (2S)-mesitylalanine；3-(2,4,6-trimethylphenyl)-D,L-alanine；(2S)-2-azaniumyl-3-(2,4,6-trimethylphenyl)propanoate
• CAS: 146277-47-6
• 化学式: C₁₂H₁₇NO₂
• 分子量: 207.272
• InChiKey: CRNOZLNQYAUXRK-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,4,6-三甲基苯丙氨酸 在 盐酸 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.5h， 生成 N^α-tert-butyloxycarbonyl-2',6'-dimethyl-L-tyrosyl-L-prolyl-2',4',6'-trimethyl-L-phenylalanyl-L-phenylalanylamide
  参考文献：
  名称：

  Bifunctional [2‘,6‘-Dimethyl-l-tyrosine]endomorphin-2 Analogues Substituted at Position 3 with Alkylated Phenylalanine Derivatives Yield Potent Mixed μ-Agonist/δ-Antagonist and Dual μ-Agonist/δ-Agonist Opioid Ligands

  摘要：

  Endomorphin-2 (H-Tyr-Pro-Phe-Phe-NH2) and [Dmt(1)]EM-2 (Dmt = 2',6'-dimethyl-L-tyrosine) analogues, containing alkylated Phe(3) derivatives, 2'-monomethyl (2, 2'), 3',5'- and 2',6'-dimethyl (3, 3', and 4', respectively), 2',4',6'-trimethyl (6, 6'), 2'-ethyl-6'-methyl (7, 7'), and 2'-isopropyl-6'-methyl (8, 8') groups or Dmt (5, 5'), had the following characteristics: (i) [Xaa(3)]EM-2 analogues exhibited improved mu- and delta-opioid receptor affinities. The latter, however, were inconsequential (K-i(delta) = 491-3451 nM). (ii) [Dmt(1),Xaa(3)]EM-2 analogues enhanced mu- and delta-opioid receptor affinities (K-i(mu) = 0.069-0.32 nM; K-i(delta) = 1.83-99.8 nM) without kappa-opioid receptor interaction. (iii) There were elevated mu-bioactivity (IC50 = 0.12-14.4 nM) and abolished delta-agonism (IC50 > 10 mu M in 2', 3', 4', 5', 6'), although 4' and 6' demonstrated a potent mixed mu-agonism/delta-antagonism (for 4', IC50 mu = 0.12 and pA(2) = 8.15; for 6', IC50 mu = 0.21 nM and pA(2) = 9.05) and 7' was a dual mu-agonist/delta-agonist (IC50 mu = 0.17 nM; IC50 delta = 0.51 nM).

  DOI：

  10.1021/jm061238m
• 作为产物：
  描述：

  (2S)-mesitylalanine ethyl ester 在 lithium hydroxide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 24.0h， 以80%的产率得到2,4,6-三甲基苯丙氨酸
  参考文献：
  名称：

  A unified approach to mesityl amino acids based on Sharpless dihydroxylation

  摘要：

  Enantioselective syntheses of two mesityl (2,4,6-trimethylphenyl) amino acids are described. Starting from ethyl 3-mesityl-2-propenoate both enantiomeric dihydroxy esters 5 were prepared in excellent yield and enantiomeric purity (>99% ee) by Sharpless dihydroxylation. Each diol was converted into ethyl 3-azido-2-hydroxy-3-mesitylpropanoate 3 which is the common intermediate. Compound (2S,3S)-3 was transformed into Fmoc-D-mesitylglycine D-1 and Fmoc-L-mesitylalanine L-2 through two four-step-sequences. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2007.10.041

文献信息

• INSULIN VITAMIN D CONJUGATES
  申请人：EXTEND BIOSCIENCES, INC.

  公开号：US20160114001A1

  公开（公告）日：2016-04-28

  The invention provides non-hormonal vitamin D conjugated to insulin peptides that result in the peptides having increased absorption, bioavailability or circulating half-life when compared to non-conjugated forms. The vitamin D targeting groups are coupled to the insulin peptides via the third carbon on the vitamin D backbone.

  该发明提供了非激素性维生素D与胰岛素肽结合，导致这些肽的吸收、生物利用度或循环半衰期比未结合形式增加。维生素D靶向基团通过维生素D骨架上的第三个碳与胰岛素肽结合。
• THERAPEUTIC VITAMIN D CONJUGATES
  申请人：Extend Biosciences, Inc.

  公开号：US20160113993A1

  公开（公告）日：2016-04-28

  The invention provides non-hormonal vitamin D conjugated to apelin proteins that result in increased absorption, bioavailability or circulating half-life when compared to non-conjugated forms. In some embodiments, the vitamin D targeting groups are coupled to the apelin proteins via the third carbon on the vitamin D backbone.

  该发明提供了非激素维生素D与apelin蛋白结合形成的产物，与非结合形式相比，其吸收、生物利用度或循环半衰期增加。在某些实施方式中，维生素D的靶向基团通过维生素D骨架上的第三个碳与apelin蛋白偶联。
• PEPTIDE PHARMACEUTICALS FOR INSULIN RESISTANCE
  申请人：NESTOR John J.

  公开号：US20140349928A1

  公开（公告）日：2014-11-27

  Described herein are methods of syntheses and therapeutic uses of covalently modified peptides and/or proteins. The covalently modified peptides and/or proteins allow for improved pharmaceutical properties of peptide and protein-based therapeutics.

  本文描述了共价修饰肽和/或蛋白质的合成方法和治疗用途。共价修饰的肽和/或蛋白质可以提高基于肽和蛋白质的治疗药物的药理特性。
• IMPROVED PEPTIDE PHARMACEUTICALS
  申请人：EUMEDERIS PHARMACEUTICALS, INC.

  公开号：US20150307550A1

  公开（公告）日：2015-10-29

  Described herein are methods of syntheses and therapeutic uses of covalently modified peptides and/or proteins. The covalently modified peptides and/or proteins allow for improved pharmaceutical properties of peptide and protein-based therapeutics.

  本文描述了共价修饰肽和/或蛋白质的合成方法和治疗用途。共价修饰的肽和/或蛋白质可以改善基于肽和蛋白质的治疗药物的药理特性。
• [EN] IMPROVED PEPTIDE PHARMACEUTICALS FOR INSULIN RESISTANCE<br/>[FR] PRODUITS PHARMACEUTIQUES PEPTIDIQUES AMÉLIORÉS CONTRE L'INSULINORÉSISTANCE
  申请人：MEDERIS DIABETES LLC

  公开号：WO2015184177A1

  公开（公告）日：2015-12-03

  Described herein are methods of syntheses and therapeutic uses of covalently modified peptides and/or proteins. The covalently modified peptides and/or proteins allow for improved pharmaceutical properties of peptide and protein-based therapeutics.

  本文描述了合成和治疗用途的共价修饰肽和/或蛋白质的方法。这些共价修饰的肽和/或蛋白质可以改善基于肽和蛋白质的治疗药物的药理特性。