1-(4-methoxy-benzyldisulfanyl)-2,4-dinitrobenzene | 191401-86-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(4-methoxy-benzyldisulfanyl)-2,4-dinitrobenzene
• 英文别名: 1-(4-methoxybenzyldisulfanyl)-2,4-dinitrobenzene；2,4-dinitrophenyl-4-methoxybenzyl disulfide；4-methoxybenzyl 2,4-dinitrophenyl disulfide；1-[(4-Methoxyphenyl)methyldisulfanyl]-2,4-dinitrobenzene
• CAS: 191401-86-2
• 化学式: C₁₄H₁₂N₂O₅S₂
• 分子量: 352.392
• InChiKey: HWHRGESZGZPOAO-UHFFFAOYSA-N

物化性质

• 沸点：
  499.0±45.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  152
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(4-methoxy-benzyldisulfanyl)-2,4-dinitrobenzene 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 4.5h， 生成 (2R,3R), 3-benzyloxycarbonylamino-2-[4-methoxybenzylsulfanyl]-5-[dibenzyloxyphosphoryl]-pent-4-enoic acid tertiobutyl ester
  参考文献：
  名称：

  Investigation of Subsite Preferences in Aminopeptidase A (EC 3.4.11.7) Led to the Design of the First Highly Potent and Selective Inhibitors of This Enzyme

  摘要：

  The study of the physiological roles of the membrane-bound zinc-aminopeptidase A (glutamyl aminopeptidase, EC 3.4.11.7) needs the design of efficient and selective inhibitors of this enzyme. An acute exploration of aminopeptidase A active site was performed by a combinatorial approach using (3-amino-2-mercapto-acyl)dipeptides able to sc its S-1, S-1', and S-2' subsites. This analysis confirmed that the S-1 subsite is optimally blocked by a glutamate or isosteric residues and demonstrated that the S-1' subsite is hydrophobic whereas the S-2' subsite recognizes preferentially negatively charged residues derived from aspartic acid. The optimization of these structural parameters led to the synthesis of nanomolar and subnanomolar inhibitors of aminopeptidase A such as H3N+CH(CH2CH2SO3-)CH(SH)CO-Ile-(3-COOH)Pro that exhibits a K-i of 0.87 nM. The best compounds were synthesized by a stereochemically controlled route. These first described highly potent inhibitors could allow studies about the role of physiological substrates of APA such as angiotensin II- and cholecystokinin CCK8 in the central nervous system.

  DOI：

  10.1021/jm9903040
• 作为产物：
  描述：

  2,4-二硝基苯硫氯 、 4-甲氧基苄硫醇 在 silver(I) acetate 作用下， 以80%的产率得到1-(4-methoxy-benzyldisulfanyl)-2,4-dinitrobenzene
  参考文献：
  名称：

  2,4-Dinitrophenyl 4-Methoxybenzyl Disulfide:  A New Efficient Reagent for the Electrophilic Sulfenylation of β-Amino Ester Enolates

  摘要：

  DOI：

  10.1021/jo9623853

文献信息

• MIXED INHIBITORS OF AMINOPEPTIDASE N AND NEPRILYSIN
  申请人：PHARMALEADS

  公开号：US20150299116A1

  公开（公告）日：2015-10-22

  Mixed inhibitors of aminopeptidase N and neprilysin are disclosed. Pharmaceutical compositions containing at least one of these compounds, used alone or in combination with morphine and derivatives thereof, endocannabinoids and inhibitors of endocannabinoid metabolism, GABA derivatives such as gabapentin or pregabalin, duloxetine or methadone, can be used as an analgesic, anxiolytic, antidepressant or anti-inflammatory.

  披露了氨肽酶N和神经肽酶的混合抑制剂。含有至少其中一种化合物的药物组合物，可单独使用或与吗啡及其衍生物、内源大麻素和内源大麻素代谢抑制剂、GABA衍生物如加巴喷丁或普雷加巴林、度洛西汀或美沙酮结合使用，可用作镇痛剂、抗焦虑剂、抗抑郁剂或抗炎药。
• Straightforward and Diastereoselective Synthesis of Tetrafunctionalized Thiol Synthons for the Design of Metallopeptidase Inhibitors
  作者：Christelle David、Laurent Bischoff、Bernard P Roques、Marie-Claude Fournié-Zaluski

  DOI：10.1016/s0040-4020(99)00922-9

  日期：2000.1

  Tetrafunctionalized thiol-containing synthons with different side-chains have been prepared with good yields by a straightforward diastereoselective and general methodology. The key step of the synthesis consisted of a tandem reduction and Wittig–Horner reaction, which conserved the stereochemistry of the starting material. The method was generalized to different side-chains, allowing synthons for

  已经通过简单的非对映选择性和通用方法以良好的产率制备了具有不同侧链的四官能化的含硫醇的合成子。合成的关键步骤包括串联还原反应和Wittig-Horner反应，这保留了起始原料的立体化学。该方法被推广到不同的侧链，使合成用于设计各种锌金属肽酶抑制剂的合成子变得容易。
• Type b botulism toxin inhibitors
  申请人：——

  公开号：US20040176333A1

  公开（公告）日：2004-09-09

  The invention relates to novel compounds of genera formula (I), with inhibitory properties for the type B botulism toxin activity, the methods for preparation thereof and corresponding pharmaceutical compositions. The invention further relates to corresponding pharmaceutical compositions. 1

  该发明涉及一般式（I）的新化合物，具有对B型肉毒杆菌毒素活性的抑制性能，以及其制备方法和相应的药物组成。该发明还涉及相应的药物组成。
• Small tripeptide surrogates with low nanomolar affinity as potent inhibitors of the botulinum neurotoxin B metallo-proteolytic activity
  作者：Armand Blommaert、Serge Turcaud、Christine Anne、Bernard P Roques

  DOI：10.1016/j.bmc.2004.03.006

  日期：2004.6

  Botulinum neurotoxin type B is a high-weight (150 kDa) protein produced by the anaerobic bacillus Clostridium botulinum. This metallo-protease neurotoxin cleaves synaptobrevin, a protein, which is crucial to neurotransmission, resulting in the muscle paralysis, which characterizes botulism. Inhibition of the metallo-peptidase activity is a possible approach to obtain specific therapeutics to treat botulism

  B型肉毒杆菌神经毒素是一种由厌氧杆菌肉毒梭菌产生的高重量（150 kDa）蛋白。这种金属蛋白酶神经毒素会裂解突触短纤维蛋白（一种对神经传递至关重要的蛋白质），导致肌肉麻痹，这是肉毒中毒的特征。抑制金属肽酶活性是获得治疗肉毒中毒的特定疗法的可能方法。我们以前曾报道过成功尝试用新的选择性氨基硫醇抑制剂（其Ki值在15至20纳摩尔范围内）来阻断这种神经毒素的蛋白水解活性。为了增加该第一系列抑制剂的亲和力和生物利用度，我们通过比较一系列包含亲本结构细微但重要的变体的配体，优化了适合酶P（1）亚位点的残基。此外，该策略通过减少可能的立体异构体数量，简化了BoNT / B抑制剂的合成。因此，与产生具有Ki值在低纳摩尔范围内的第一种假三肽抑制剂的初始特权结构相比，我们能够在提高抑制效力的同时减小尺寸。
• Development of Potent Inhibitors of Botulinum Neurotoxin Type B
  作者：Christine Anne、Serge Turcaud、Jean Quancard、Franck Teffo、Hervé Meudal、Marie-Claude Fournié-Zaluski、Bernard P. Roques

  DOI：10.1021/jm0300680

  日期：2003.10.1

  Botulinum neurotoxins are the most potent toxins known to date. They are zinc-metalloproteases able to cleave selectively an essential component of neurotransmitter exocytosis, causing the syndrome of botulism characterized by a flaccid paralysis. There is a great interest in designing antagonists of the action of these toxins. One way is to inhibit their catalytic activity. In this study, we report the design of such inhibitors directed toward BoNT/B. A study of the S-1 subsite specificity, using several beta-amino thiols, has shown that this subsite prefers a p-carboxybenzyl moiety. The specificity of the S-1' and S-2' subsites was studied using two libraries of pseudotripeptides containing the S-1 synthon derived from the best beta-amino thiol tested. Finally, a selection of various non natural amino acids for the recognition of the "prime" domain led to the most potent inhibitor of BoNT/B described to date with a K-i value of 20 nM.