N-[(4-甲氧基苯基)甲基氨基]氨基甲酸叔丁酯 | 150767-02-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: N-[(4-甲氧基苯基)甲基氨基]氨基甲酸叔丁酯
• 英文名称: N-t-butoxycarbonyl-N'-4-methoxybenzyl hydrazine
• 英文别名: N-1-(tert-butoxycarbonyl)-N-2-<(4-methoxyphenyl)methyl>hydrazine；tert-butyl 2-(4-methoxybenzyl)hydrazine-1-carboxylate；tert-butyl 2-(4-methoxybenzyl)hydrazinecarboxylate；N-PMB-tert-butyl carbazate；tert-butyl-3-(4-methoxyphenyl-methyl)-carbazate；tert-butyl N-[(4-methoxyphenyl)methylamino]carbamate
• CAS: 150767-02-5
• 化学式: C₁₃H₂₀N₂O₃
• 分子量: 252.313
• InChiKey: LAAOJPYAGIBKBK-UHFFFAOYSA-N

物化性质

• 密度：
  1.080±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  59.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2928000090

反应信息

• 作为反应物：
  描述：

  N-[(4-甲氧基苯基)甲基氨基]氨基甲酸叔丁酯 在 potassium carbonate 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 32.0h， 生成 N'-((2S,3S)-3-Amino-2-hydroxy-4-phenyl-butyl)-N'-(4-methoxy-benzyl)-hydrazinecarboxylic acid tert-butyl ester
  参考文献：
  名称：

  Aza-Peptide Analogs as Potent Human Immunodeficiency Virus Type-1 Protease Inhibitors with Oral Bioavailability

  摘要：

  A series of aza-peptide analogs with a (hydroxyethyl)hydrazine isostere has been synthesized as HIV-1 protease inhibitors using a simple synthetic scheme. Structure-activity studies based on the X-ray of a previously described inhibitor-enzyme complex led to potent inhibitors with antiviral activity in the low-nanomolar range. The S-configuration of the transition-state hydroxyl group was preferred in this series. Small modifications of the P2P3 and P-2'P-3' substituents had little effect on enzyme inhibition but greatly influenced the pharmacokinetic profile. As a result of these studies, the symmetrically acylated compound 8a and its close analog 24a bearing a methyl carbamate in P-3 and an ethyl carbamate in P-3' position were identified as potent inhibitors with plasma concentrations exceeding antiviral ED(50) values 150-fold following oral application in mice.

  DOI：

  10.1021/jm960022p
• 作为产物：
  描述：

  4-甲氧基苯甲醛 在 palladium 10% on activated carbon 、 sodium formate 作用下， 以 乙醇 、 水 、 异丙醇 、 甲苯 为溶剂， 反应 16.0h， 生成 N-[(4-甲氧基苯基)甲基氨基]氨基甲酸叔丁酯
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Hydrazone Derivatives as Antifungal Agents

  摘要：

  新兴酵母菌是系统性感染中最常见的病原体之一，死亡率极高，因此迫切需要开发具有特异性、有效且无毒的抗真菌药物来应对这一问题。本研究中，我们获得了35种醛类、肼类和酰肼类化合物，并在体外筛选中评估了它们对Candida属（C. parapsilosis、C. tropicalis、C. krusei、C. albicans、C. glabrata和C. lusitaneae）和Trichosporon asahii的抗真菌活性。我们对筛选出的活性化合物对10株临床分离的C. parapsilosis和10株T. asahii的最低抑菌浓度（MICs）进行了测定。化合物4-吡啶-2-基苯甲醛（13a）和叔丁基-(2Z)-2-(3,4,5-三羟基苄脒)酰肼羧酸酯（7b）分别在16-32 μg/mL和8-16 μg/mL的范围内显示出最有希望的MIC值。我们评估了这些化合物对细胞膜和细胞壁稳定性的影响，结果表明这些化合物作用于真菌细胞膜。通过细胞活力测定和碱性彗星试验评价了其细胞毒性。化合物13a在活性浓度下不具有细胞毒性。这些结果支持了发现有希望的候选药物用于开发新型抗真菌药物。

  DOI：

  10.3390/molecules20059229

文献信息

• AMINO PYRAZOLE COMPOUND
  申请人：Burkholder Timothy Paul

  公开号：US20100152181A1

  公开（公告）日：2010-06-17

  The present invention provides amino pyrazole compounds useful in the treatment of chronic myeloproliferative disorders and various cancers, e.g., glioblastoma, breast cancer, multiple myeloma, prostate cancer, and leukemias.

  本发明提供了一种氨基吡唑化合物，可用于治疗慢性骨髓增生性疾病和各种癌症，例如胶质母细胞瘤、乳腺癌、多发性骨髓瘤、前列腺癌和白血病。
• Antiretroviral hydrazine derivatives
  申请人：Novartis Corporation

  公开号：US05753652A1

  公开（公告）日：1998-05-19

  The invention relates to compounds of formula ##STR1## and salts, pharmaceutical compositions, intermediates and processes of preparation thereof.

  本发明涉及具有公式##STR1##的化合物及其盐、药物组合物、中间体及其制备方法。
• Synthesis, Antileishmanial Activity and in silico Studies of Aminoguanidine Hydrazones (AGH) and Thiosemicarbazones (TSC) Against Leishmania chagasi Amastigotes
  作者：Thiago M. de Aquino、Paulo H. B. França、Érica E. E. S. Rodrigues、Igor. J.S. Nascimento、Paulo F. S. Santos-Júnior、Pedro G. V. Aquino、Mariana S. Santos、Aline C. Queiroz、Morgana V. Araújo、Magna S. Alexandre-Moreira、Raiza R. L. Rodrigues、Klinger A. F. Rodrigues、Johnnatan D. Freitas、Jacques Bricard、Mario R. Meneghetti、Jean-Jacques Bourguignon、Martine Schmitt、Edeildo F. da Silva-Júnior、João X. de Araújo-Júnior

  DOI：10.2174/1573406417666210216154428

  日期：2022.2

  Leishmaniasis is a worldwide health problem, highly endemic in developing countries. Among the four main clinical forms of the disease, visceral leishmaniasis is the most severe, fatal in 95% of cases. The undesired side-effects from first-line chemotherapy and the reported drug resistance search for effective drugs that can replace or supplement those currently used an urgent need. Aminoguanidine hydrazones (AGH's) have been explored for exhibiting a diverse spectrum of biological activities, in particular the antileishmanial activity of MGBG. The bioisosteres thiosemicarbazones (TSC's) offer a similar biological activity diversity, including antiprotozoal effects against Leishmania species and Trypanosoma cruzi.

  Considering the impact of leishmaniasis worldwide, this work aimed to design, synthesize, and perform a screening upon L. chagasi amastigotes and for the cytotoxicity of the small "in-house" library of both AGH and TSC derivatives and their structurally-related compounds.

  A set of AGH's (3-7), TSC's (9, 10), and semicarbazones (11) were initially synthesized. Subsequently, different semi-constrained analogs were designed and also prepared, including thiazolidines (12), dihydrothiazines (13), imidazolines (15), pyrimidines (16, 18) azines (19, 20), and benzotriazepinones (23-25). All intermediates and target compounds were obtained with satisfactory yields and exhibited spectral data consistent with their structures. All final compounds were evaluated against L. chagasi amastigotes and J774.A1 cell line. Molecular docking was performed towards trypanothione reductase using GOLD® software.

  The AGH's 3i, 4a, and 5d, and the TSC's 9i, 9k, and 9o were selected as valuable hits. These compounds presented antileishmanial activity compared with pentamidine, showing IC50 values ranged from 0.6 to 7.27 μM, maximal effects up to 55.3%, and satisfactory SI values (ranged from 11 to 87). On the other hand, most of the resulting semi-constrained analogs were found cytotoxic or presented reduced antileishmanial activity. In general, TSC class is more promising than its isosteric AGH analogs, and the beneficial aromatic substituent effects are not similar in both series. In silico studies have suggested that these hits are capable of inhibiting the trypanothione reductase from the amastigote forms.

  The promising antileishmanial activity of three AGH’s and three TSC’s was characterized. These compounds presented antileishmanial activity compared with PTD, showing IC50 values ranged from 0.6 to 7.27 μM, and satisfactory SI values. Further pharmacological assays involving other Leishmania strains are under progress, which will help to choose the best hits for in vivo experiments.

  背景：利什曼病是全球性健康问题，在发展中国家高度流行。在该病的四种主要临床形式中，内脏利什曼病是最严重的，95%的病例会致命。由于一线化疗药物的不良副作用和报道的药物耐药性，迫切需要寻找可以替代或补充当前使用的有效药物。氨基胍脒肼酮（AGH）已被探索用于展示多样的生物活性，特别是MGBG的抗利什曼病活性。生物同功异构体硫脲半胱氨酮（TSC）提供类似的生物活性多样性，包括对利什曼病和克氏锥虫的抗原虫效应。 目的：考虑到利什曼病在全球范围内的影响，本研究旨在设计、合成并对L. chagasi阿马斯蒂果虫进行筛选，以及对小型“内部”AGH和TSC衍生物及其结构相关化合物的细胞毒性进行评估。 方法：首先合成了一组AGH（3-7）、TSC（9, 10）和半胱氨酮（11）。随后，设计并制备了不同的半约束类似物，包括噻唑烷（12）、二氢噻嗪（13）、咪唑烷（15）、嘧啶（16, 18）、吲哚烷（19, 20）和苯并三唑环酮（23-25）。所有中间体和目标化合物均以满意的收率获得，并展示了与其结构一致的光谱数据。所有最终化合物均对L. chagasi阿马斯蒂果虫和J774.A1细胞系进行了评估。使用GOLD®软件对其进行了针对巯基还原酶的分子对接。 结果：AGH的3i、4a和5d以及TSC的9i、9k和9o被选为有价值的命中物。这些化合物与五环胺相比具有抗利什曼病活性，IC50值范围从0.6到7.27μM，最大效果高达55.3％，满意的SI值（范围从11到87）。另一方面，大多数结果的半约束类似物被发现具有细胞毒性或具有降低的抗利什曼病活性。总体而言，TSC类比其同功异构AGH类更有前景，而有益的芳香族取代作用在两个系列中并不相似。计算机模拟研究表明这些命中物能够抑制阿马斯蒂果虫的巯基还原酶。 结论：三种AGH和三种TSC的有前景的抗利什曼病活性得到了表征。这些化合物与PTD相比具有抗利什曼病活性，IC50值范围从0.6到7.27μM，SI值满意。正在进行涉及其他利什曼病菌株的进一步药理学评估，这将有助于选择最佳的命中物进行体内实验。
• Exploration of a Au(<scp>i</scp>)-mediated three-component reaction for the synthesis of DNA-tagged highly substituted spiroheterocycles
  作者：Mateja Klika Škopić、Suzanne Willems、Bernd Wagner、Justin Schieven、Norbert Krause、Andreas Brunschweiger

  DOI：10.1039/c7ob02347b

  日期：——

  We demonstrate a Au(I)-mediated three-component reaction to DNA-tagged highly substituted 6-oxa-1,2-diazaspiro[4.4]nonanes from either DNA-coupled aldehydes, hydrazides, or alkynols. The choice of the starting material coupled to the DNA tag was critial for the purity of the product as the DNA-aldehyde conjugate yielded the purest products, whereas the alkynol- and hydrazide conjugates returned complex

  我们展示了Au（I）介导的三组分反应，从DNA偶联的醛，酰肼或炔醇中脱氧核糖核酸标记的高度取代的6-oxa-1,2-二氮杂螺[4.4]壬烷。对于DNA纯度而言，选择与DNA标签偶联的起始原料至关重要，因为DNA-醛缀合物可产生最纯净的产物，而炔醇-酰肼缀合物可返回复杂的产物混合物。该反应与胸腺嘧啶，胞嘧啶和令人惊奇的腺嘌呤-DNA相容，而含鸟嘌呤的DNA链在反应条件下降解。
• Facile synthesis of potent HIV-1 protease inhibitors containing a novel pseudo-symmetric dipeptide isostere
  作者：Hing L. Sham、David A. Betebenner、Chen Zhao、Norman E. Wideburg、Ayda Saldivar、Dale J. Kempf、Jacob J. Plattner、Daniel W. Norbeck

  DOI：10.1039/c39930001052

  日期：——

  A series of potent inhibitors of the HIV-1 protease containing a novel pseudo-symmetric dipeptide isostere 3 was synthesized via ring opening of a protected epoxide with various substituted hydrazines.

  通过用各种取代的肼将受保护的环氧化物开环，合成了一系列含有新型伪对称二肽等位基因3的有效的HIV-1蛋白酶抑制剂。