(S)-methyl 2-(tert-butoxycarbonylamino)-3-(2,5-diiodo-1H-imidazol-4-yl)propanoate

• 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-diiodo-1H-imidazol-4-yl)propanoate
• 英文别名: Boc-L-His(2,5-diiodo)-OMe；methyl (2S)-3-(2,4-diiodo-1H-imidazol-5-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• 化学式: C₁₂H₁₇I₂N₃O₄
• 分子量: 521.094
• InChiKey: BLJGRKKJSKVSJK-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 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-diiodo-1H-imidazol-4-yl)propanoate 在 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 N(α)-t-butoxycarbonyl-2,5-di-iodo-L-histidine
  参考文献：
  名称：

  含促甲状腺激素释放激素（TRH）类似物的环修饰的1-组氨酸的合成与生物学

  摘要：

  促甲状腺激素释放激素（TRH）类似物，在C-2和/或C-5位置带有卤素基团（Cl，Br和I），以及烷基（CH 3，C 2 H 5，C 3 H 7，CH合成中央组氨酸残基咪唑环N-1位置的2 C 6 H 5）并评估在HEK mTRHR1和HEK mTRHR2表达细胞上的受体结合，钙动员（FLIPR）和IP-1分析线。最有前途的模拟7k在IP-1分析中显示对HEK mTRH-R2受体亚型具有925倍的选择性，在FLIPR分析中显示对HEK mTRH-R2受体亚型具有272倍的选择性，对HEK TRH-R2受体亚型具有21倍的受体结合特异性。在脑膜竞争结合试验中体外评估了肽7k，并在体内存在TRH-DE的情况下进行了稳定性分析。在戊巴比妥诱导的睡眠试验中，类似物7k的睡眠时间减少了76％以上，并且体内血液中的TSH水平升高幅度相对较小。TRH-R1和TRH-R2的计算同源性建模以及与最有效的7k

  DOI：

  10.1016/j.ejmech.2016.01.038
• 作为产物：
  描述：

  N-叔丁基氧羰基-L-组氨酸甲酯 在 N-碘代丁二酰亚胺 作用下， 以 乙腈 为溶剂， 反应 24.0h， 生成 (S)-methyl 2-(tert-butoxycarbonylamino)-3-(2,5-diiodo-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）。
• Ring-Modified Histidine-Containing Cationic Short Peptides Exhibit Anticryptococcal Activity by Cellular Disruption
  作者：Komal Sharma、Shams Aaghaz、Indresh Kumar Maurya、Shreya Singh、Shivaprakash M. Rudramurthy、Vinod Kumar、Kulbhushan Tikoo、Rahul Jain

  DOI：10.3390/molecules28010087

  日期：——

  a series of ring-modified histidine-containing short cationic peptides exhibiting anticryptococcal activity via membrane lysis. The N-1 position of histidine was benzylated, followed by iodination at the C-5 position via electrophilic iodination, and the dipeptides were obtained after coupling with tryptophan. In vitro analysis revealed that peptides Trp-His[1-(3,5-di-tert-butylbenzyl)-5-iodo]-OMe

  继发于真菌感染的临床并发症（如隐球菌性脑膜炎）的描述以及大量人群中同时出现的多药耐药性需要开发新型抗真菌药。在此，我们报告了一系列通过膜裂解表现出抗隐球菌活性的环修饰的含组氨酸短阳离子肽。组氨酸N-1位苄基化，C-5位亲电碘化，与色氨酸偶联得到二肽。体外分析表明，肽 Trp-His[1-(3,5-二叔丁基苄基)-5-碘]-OMe（10 天，IC50 = 2.20 μg/mL；MIC = 4.01 μg/mL）和 Trp- His[1-(2-iodophenyl)-5-iodo)]-OMe（10o，IC50 = 2.52 μg/mL；MIC = 4.59 μg/mL）对梭状芽孢杆菌具有良好的抗真菌活性。新型冠状病毒。当与标准药物两性霉素 B (Amp B) 联合给药时，观察到显着的协同作用，肽和 Amp B 的效力增加 4 到 16 倍。使用 SEM 和 TEM 的电子显微镜分析表明，二肽主
• Synthesis and biology of ring-modified l-Histidine containing thyrotropin-releasing hormone (TRH) analogues
  作者：Chhuttan L. Meena、Avinash Thakur、Prajwal P. Nandekar、Shyam S. Sharma、Abhay T. Sangamwar、Rahul Jain

  DOI：10.1016/j.ejmech.2016.01.038

  日期：2016.3

  Thyrotropin-releasing hormone (TRH) analogues bearing halogen groups (Cl, Br and I) at the C-2 and/or C-5 position, and the alkyl group (CH3, C2H5, C3H7, CH2C6H5) at the N-1 position of the imidazole ring of the central histidine residue were synthesized and evaluated for the receptor binding, calcium mobilization (FLIPR), and IP-1 assay at the HEK mTRHR1 and HEK mTRHR2 expressing cell lines. The most

  促甲状腺激素释放激素（TRH）类似物，在C-2和/或C-5位置带有卤素基团（Cl，Br和I），以及烷基（CH 3，C 2 H 5，C 3 H 7，CH合成中央组氨酸残基咪唑环N-1位置的2 C 6 H 5）并评估在HEK mTRHR1和HEK mTRHR2表达细胞上的受体结合，钙动员（FLIPR）和IP-1分析线。最有前途的模拟7k在IP-1分析中显示对HEK mTRH-R2受体亚型具有925倍的选择性，在FLIPR分析中显示对HEK mTRH-R2受体亚型具有272倍的选择性，对HEK TRH-R2受体亚型具有21倍的受体结合特异性。在脑膜竞争结合试验中体外评估了肽7k，并在体内存在TRH-DE的情况下进行了稳定性分析。在戊巴比妥诱导的睡眠试验中，类似物7k的睡眠时间减少了76％以上，并且体内血液中的TSH水平升高幅度相对较小。TRH-R1和TRH-R2的计算同源性建模以及与最有效的7k
• 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.