(S)-methyl 2-(tert-butoxycarbonylamino)-3-(2,5-dibromo-1H-imidazol-4-yl)propanoate | 83468-76-2

• 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: (S)-methyl 2-(tert-butoxycarbonylamino)-3-(2,5-dibromo-1H-imidazol-4-yl)propanoate
• 英文别名: methyl (2S)-3-(2,4-dibromo-1H-imidazol-5-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• CAS: 83468-76-2
• 化学式: C₁₂H₁₇Br₂N₃O₄
• 分子量: 427.093
• InChiKey: YVOXVHAAXXXSHD-ZETCQYMHSA-N

物化性质

• 密度：
  1.655±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  93.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-methyl 2-(tert-butoxycarbonylamino)-3-(2,5-dibromo-1H-imidazol-4-yl)propanoate 在 palladium on activated charcoal 、 Rh on carbon sodium hydroxide 、 Amberlite IR 45 (acetate form) 、 氢气 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 甲醇 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.5h， 生成 大鼠转铁蛋白
  参考文献：
  名称：

  Brown, Tom; Jones, John H.; Richards, John D., Journal of the Chemical Society. Perkin transactions I, 1982, # 7, p. 1553 - 1562

  摘要：

  DOI：
• 作为产物：
  描述：

  N-叔丁基氧羰基-L-组氨酸甲酯 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 乙腈 为溶剂， 反应 24.0h， 生成 (S)-methyl 2-(tert-butoxycarbonylamino)-3-(2,5-dibromo-1H-imidazol-4-yl)propanoate
  参考文献：
  名称：

  Synthesis of CNS active thyrotropin-releasing hormone (TRH)-like peptides: Biological evaluation and effect on cognitive impairment induced by cerebral ischemia in mice

  摘要：

  Thyrotropin-releasing hormone (TRH)-like peptides were synthesized by replacing critical histidine and pGlu residues in the native peptide. The peptides were evaluated in vitro for receptor binding activity assay and in the cell functional assay; the peptides exhibit selective basal signaling agonist behavior toward TRH-R2. For example, peptides 8a, 8b, 8c, 8f, 8h, 8l and 12d activated TRH-R2 with potency (EC50) of 0.53 mu M, 0.048 mu M, 0.05 mu M, 0.006 mu M, 0.31 mu M, 0.034 mu M and 0.004 mu M, respectively. In contrast for signaling activation of TRH-R1, the same peptide required higher concentration of 19.35 mu M, 3.98 mu M, 2.54 mu M, 0.287 mu M, 11.28 mu M, 0.986 mu M and 0.944 mu M, respectively. The results showed that peptides were 36.5, 82.9, 50.8, 47.8, 36.3, 32.6 and 235-fold selective to TRH-R2 receptor subtype. The peptides were investigated for CNS activity at 10 mu mol/kg in pentobarbital-induced sleep assay study. Peptides 8c (16.5 +/- 1.4 min) and 8l (16.5 +/- 2.1 min) displayed excellent CNS activity. In an in vivo study, peptide 8c did not cause significant change in the rat plasma TSH levels. The peptide 8c was further investigated for neuroprotective potential, and significantly reduced infracts volume and neurological score in the focal cerebral ischemia model in mice. Peptide 8c also significantly lowered MDA levels, indicating reduction of oxidative and enhanced percentage cell survival in CA1 region, when compared to ischemic brain. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.07.022

文献信息

• Mono- and di-halogenated histamine, histidine and carnosine derivatives are potent carbonic anhydrase I, II, VII, XII and XIV activators
  作者：Mohamed-Chiheb Saada、Daniela Vullo、Jean-Louis Montero、Andrea Scozzafava、Claudiu T. Supuran、Jean-Yves Winum

  DOI：10.1016/j.bmc.2014.07.005

  日期：2014.9

  Mono- and di-halogenated histamines, l-histidine methyl ester derivatives and carnosine derivatives incorporating chlorine, bromine and iodine were prepared and investigated as activators of five carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic hCA I, II and VII, and the transmembrane hCA XII and XIV. All of them were activated in a diverse manner by the investigated compounds, with a distinct

  制备了单和二卤代组胺，1-组氨酸甲酯衍生物和结合了氯，溴和碘的肌肽衍生物，并研究了它们作为五种碳酸酐酶（CA，EC 4.2.1.1）同工型的活化剂，它们分别是胞质hCA I，II和II。 VII，以及跨膜hCA XII和XIV。所有这些化合物均由所研究的化合物以多种方式活化，具有独特的活化特性。
• Synthesis of ring-halogenated histidines and histamines
  作者：Rahul Jain、Bianca Avramovitch、Louis A. Cohen

  DOI：10.1016/s0040-4020(98)00068-4

  日期：1998.3

  Series of ring-halogenated histidines and histamines have been synthesized from the suitably protected parent bioimidazoles. The 5-X and 2,5-X2-derivatives are obtained by direct electrophilic halogenation while 2-X derivatives (X= Br and I) are prepared by regiospecific electrophilic dehalogenation at C-5.

  由适当保护的母体生物咪唑合成了一系列环卤代组氨酸和组胺。通过直接亲电卤化获得5-X和2,5-X 2-衍生物，而通过在C-5通过区域特异性亲电脱卤制备2-X衍生物（X = Br和I）。
• Brown, Tom; Jones, John H.; Richards, John D., Journal of the Chemical Society. Perkin transactions I, 1982, # 7, p. 1553 - 1562
  作者：Brown, Tom、Jones, John H.、Richards, John D.

  DOI：——

  日期：——
• Synthesis of CNS active thyrotropin-releasing hormone (TRH)-like peptides: Biological evaluation and effect on cognitive impairment induced by cerebral ischemia in mice
  作者：Chhuttan L. Meena、Avinash Thakur、Prajwal P. Nandekar、Abhay T. Sangamwar、Shyam S. Sharma、Rahul Jain

  DOI：10.1016/j.bmc.2015.07.022

  日期：2015.9

  Thyrotropin-releasing hormone (TRH)-like peptides were synthesized by replacing critical histidine and pGlu residues in the native peptide. The peptides were evaluated in vitro for receptor binding activity assay and in the cell functional assay; the peptides exhibit selective basal signaling agonist behavior toward TRH-R2. For example, peptides 8a, 8b, 8c, 8f, 8h, 8l and 12d activated TRH-R2 with potency (EC50) of 0.53 mu M, 0.048 mu M, 0.05 mu M, 0.006 mu M, 0.31 mu M, 0.034 mu M and 0.004 mu M, respectively. In contrast for signaling activation of TRH-R1, the same peptide required higher concentration of 19.35 mu M, 3.98 mu M, 2.54 mu M, 0.287 mu M, 11.28 mu M, 0.986 mu M and 0.944 mu M, respectively. The results showed that peptides were 36.5, 82.9, 50.8, 47.8, 36.3, 32.6 and 235-fold selective to TRH-R2 receptor subtype. The peptides were investigated for CNS activity at 10 mu mol/kg in pentobarbital-induced sleep assay study. Peptides 8c (16.5 +/- 1.4 min) and 8l (16.5 +/- 2.1 min) displayed excellent CNS activity. In an in vivo study, peptide 8c did not cause significant change in the rat plasma TSH levels. The peptide 8c was further investigated for neuroprotective potential, and significantly reduced infracts volume and neurological score in the focal cerebral ischemia model in mice. Peptide 8c also significantly lowered MDA levels, indicating reduction of oxidative and enhanced percentage cell survival in CA1 region, when compared to ischemic brain. (C) 2015 Elsevier Ltd. All rights reserved.