N-<(1,1-dimethylethoxy)carbonyl>-O-(1,1-dimethylethyl)-2,6-dimethyl-L-tyrosine methyl ester | 137650-16-9

• 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: N-<(1,1-dimethylethoxy)carbonyl>-O-(1,1-dimethylethyl)-2,6-dimethyl-L-tyrosine methyl ester
• 英文别名: Boc-2,6-dimethyl-(L)-Tyr(tBu)-OMe；N-[(1,1-dimethylethoxy)carbonyl]-O-(1,1-dimethylethyl)-2,6-dimethyl-L-tyrosine methyl ester；methyl (2S)-3-[2,6-dimethyl-4-[(2-methylpropan-2-yl)oxy]phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• CAS: 137650-16-9
• 化学式: C₂₁H₃₃NO₅
• 分子量: 379.497
• InChiKey: JWGSEBRSQKQNFZ-KRWDZBQOSA-N

物化性质

• 沸点：
  494.1±45.0 °C(Predicted)
• 密度：
  1.053±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-<(1,1-dimethylethoxy)carbonyl>-O-(1,1-dimethylethyl)-2,6-dimethyl-L-tyrosine methyl ester 在 palladium on activated charcoal N-甲基吗啉 、 lithium hydroxide 、 正丁基锂 、 氢气 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 甲苯 为溶剂， -78.0 ℃ 、34.48 kPa 条件下， 反应 5.0h， 生成 1,1-dimethylethyl <1(S)-<<4-(1,1-dimethylethoxy)-2,6-dimethylphenyl>methyl>-4-methyl-2,5-dioxo-5-<(3-phenylpropyl)amino>pentyl>carbamate
  参考文献：
  名称：

  Preparation and opioid activity of analogs of the analgesic dipeptide 2,6-dimethyl-L-tyrosyl-N-(3-phenylpropyl)-D-alaninamide

  摘要：

  A number of analogues of the recently disclosed analgesic dipeptide 2,6-dimethyl-L-tyrosyl-D-alanine-phenylpropylamide (SC-39566,2) were prepared. These analogues contained oxymethylene, aminomethylene, ketomethylene, bismethylene, and trans double bond (including vinyl fluoride) isosteric replacements for the amide bond between the D-alanine and phenylpropylamine units in 2. These compounds were tested in opioid binding assays and in the mouse writhing assay for analgesic activity. Though not as potent as 2, the oxymethylene, and trans double bond isosteres showed analgesic activity. The aminomethylene analogues also showed binding activity in subnanomolar concentrations at the mu-receptor. The amide bond between 2,6-dimethyl-L-tyrosine and D-alanine units seems to be critical for opioid activity.

  DOI：

  10.1021/jm00080a005
• 作为产物：
  描述：

  Fmoc-2,6-dimethyl-(L)-Tyr(tBu)-OMe 在 二甲胺 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 N-<(1,1-dimethylethoxy)carbonyl>-O-(1,1-dimethylethyl)-2,6-dimethyl-L-tyrosine methyl ester
  参考文献：
  名称：

  2,6-Dimethyltyrosine Analogues of a Stereodiversified Ligand Library:  Highly Potent, Selective, Non-Peptidic μ Opioid Receptor Agonists

  摘要：

  We recently reported the use of an exhaustively stereodiversified library based on endomorphin-2 (1) to discovery opioid receptor (MOR) ligands of type 2-4. Here, we report the synthesis and evaluation of 2,6-dimethyltyrosine analogues 5-10. These analogues showed improved affinity for MOR relative to 2-4. In the cases of 5 and 6, we synthesized and evaluated five stereoisomers of each, thereby discovering stereoisomers with unexpected potency, selectivity, and efficacy. These results illustrate the utility of acyclic, stereodiverse libraries.

  DOI：

  10.1021/jm025608s

文献信息

• [EN] MU OPIOID RECEPTOR LIGANDS: METHODS OF USE AND SYNTHESIS<br/>[FR] LIGANDS DE RECEPTEUR OPIOIDE MU: PROCEDES D'UTILISATION ET DE SYNTHESE
  申请人：HARVARD COLLEGE

  公开号：WO2004033414A1

  公开（公告）日：2004-04-22

  Peptidomimetic compounds derived from aralkyl substitued 8-amino-3,7- or 3,6-dihydroxy alkenoic or alkanoic acids and compositions including those compounds, as well as methods of using and making the compounds are herein described. The compounds are useful in therapeutic applications, including modulation of disease symptoms in a subject (e.g., mammal, human, dog, cat, horse). The compounds are useful as modulators of the mu opioid receptor (MOR) through their binding affinity with that receptor.

  本文描述了从芳基取代的8-氨基-3,7-或3,6-二羟基烯酸或烷酸衍生的肽类模拟化合物，以及包括这些化合物的组合物，以及使用和制备这些化合物的方法。这些化合物在治疗应用中很有用，包括调节受试者（例如，哺乳动物、人类、狗、猫、马）的疾病症状。这些化合物通过它们与μ阿片受体（MOR）的结合亲和力在调节MOR方面很有用。
• Mu opioid receptor ligands: methods of use and synthesis
  申请人：Harrison Bryce A.

  公开号：US20090093534A1

  公开（公告）日：2009-04-09

  Novel compounds and compositions including those compounds, as well as methods of using and making the compounds are herein described. The compounds are useful in therapeutic applications, including modulation of disease or disease symptoms in a subject (e.g., mammal, human, dog, cat, horse). The compounds are useful as modulators of the mu opioid receptor (MOR) through their binding affinity with that receptor.

  本文描述了包括这些化合物在内的新型化合物和组合物，以及使用和制造这些化合物的方法。这些化合物在治疗应用中有用，包括调节受试者（例如哺乳动物、人类、狗、猫、马）的疾病或疾病症状。这些化合物通过它们与μ阿片受体（MOR）的结合亲和力作为MOR的调节剂是有用的。
• US7223888B2
  申请人：——

  公开号：US7223888B2

  公开（公告）日：2007-05-29
• US7759514B2
  申请人：——

  公开号：US7759514B2

  公开（公告）日：2010-07-20
• 2,6-Dimethyltyrosine Analogues of a Stereodiversified Ligand Library:  Highly Potent, Selective, Non-Peptidic μ Opioid Receptor Agonists
  作者：Bryce A. Harrison、Gavril W. Pasternak、Gregory L. Verdine

  DOI：10.1021/jm025608s

  日期：2003.2.1

  We recently reported the use of an exhaustively stereodiversified library based on endomorphin-2 (1) to discovery opioid receptor (MOR) ligands of type 2-4. Here, we report the synthesis and evaluation of 2,6-dimethyltyrosine analogues 5-10. These analogues showed improved affinity for MOR relative to 2-4. In the cases of 5 and 6, we synthesized and evaluated five stereoisomers of each, thereby discovering stereoisomers with unexpected potency, selectivity, and efficacy. These results illustrate the utility of acyclic, stereodiverse libraries.