4-(2-tert-butoxycarbonylamino-3-methoxycarbonylpropyl)benzoic acid tert-butyl ester | 473259-72-2

• 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: 4-(2-tert-butoxycarbonylamino-3-methoxycarbonylpropyl)benzoic acid tert-butyl ester
• 英文别名: methyl (3S)-3-(N-Boc)amino-4-[4-t-butyloxycarbonyl]phenylbutanoate；tert-butyl 4-[(2S)-4-methoxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxobutyl]benzoate
• CAS: 473259-72-2
• 化学式: C₂₁H₃₁NO₆
• 分子量: 393.48
• InChiKey: XQXDZHYPWLVBOA-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  90.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(2-tert-butoxycarbonylamino-3-methoxycarbonylpropyl)benzoic acid tert-butyl ester 在 正丁基锂 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 六甲基二硅氮烷 、 三丁基氧化锡 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 127.5h， 生成 4{(2S)-2-amino-3-[1-(1-benzylcarbamoyl-(2S)-2-phenylethylcarbamoyl)-(2S)-2-(1-methyl-1H-indol-3-yl)ethylcarbamoyl]-3(S)-sulfanylpropyl}benzoic acid
  参考文献：
  名称：

  Development of Potent Inhibitors of Botulinum Neurotoxin Type B

  摘要：

  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.

  DOI：

  10.1021/jm0300680
• 作为产物：
  描述：

  N,4-bis[(1,1-dimethylethoxy)carbonyl]-L-Phe 在 N-甲基吗啉 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 3.0h， 生成 4-(2-tert-butoxycarbonylamino-3-methoxycarbonylpropyl)benzoic acid tert-butyl ester
  参考文献：
  名称：

  Development of Potent Inhibitors of Botulinum Neurotoxin Type B

  摘要：

  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.

  DOI：

  10.1021/jm0300680

文献信息

• 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。
• Thio-derived disulfides as potent inhibitors of botulinum neurotoxin type B: implications for zinc interaction
  作者：Christine Anne、Armand Blommaert、Serge Turcaud、Anne-Sophie Martin、Hervé Meudal、Bernard P Roques

  DOI：10.1016/s0968-0896(03)00450-4

  日期：2003.10

  Botulinum neurotoxin type B causes the inhibition of acetylcholine release at the neuromuscular junction resulting in a flaccid paralysis designated botulism. This occurs through the cleavage of synaptobrevin, an intracellular critical component of neurotransmitter exocytosis, by the zinc-metallopeptidase activity of the smallest subunit of the toxin. Blocking the proteolytic activity may present an

  B型肉毒杆菌神经毒素会导致神经肌肉接头处的乙酰胆碱释放受到抑制，从而导致松弛肉麻痹（称为肉毒中毒）。这是通过毒素最小的亚基的锌-金属肽酶活性对神经递质胞吐作用的细胞内关键成分-突触短纤维蛋白的裂解而发生的。阻断蛋白水解活性可能是治疗肉毒中毒的一种有吸引力的方法，因为迄今为止尚无有效的特异性药物疗法。因此，我们最近描述了一系列能够在低（10（-8）M）浓度下抑制毒素的β-氨基硫醇衍生的伪三肽。在这项研究中，蛋白质的结合特性 通过硫醇官能度的各种结构修饰来探索其活性位点，硫醇官能团被认为是有效锌离子螯合的关键结构组成。出乎意料的是，硫烷基衍生物如对称的二硫化物被证明比其硫醇对应物是更好的抑制剂，最有效的化合物显示出3.4 nM的Ki值。
• 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.