4-[2-tert-butoxycarbonylamino-3-carboxy-3-(4-methoxybenzylsulfanyl)propyl]benzoic acid tert-butyl ester | 473259-71-1

• 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-carboxy-3-(4-methoxybenzylsulfanyl)propyl]benzoic acid tert-butyl ester
• 英文别名: (2S,3S)-2-(p-methoxybenzyl)sulfenyl-3-N-Boc-amino-4-(4-t-butyloxycarbonylphenyl)butanoic acid；(2S,3S)-2-[(4-methoxyphenyl)methylsulfanyl]-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-[4-[(2-methylpropan-2-yl)oxycarbonyl]phenyl]butanoic acid
• CAS: 473259-71-1
• 化学式: C₂₈H₃₇NO₇S
• 分子量: 531.67
• InChiKey: GOJQXDUZKRZQRU-GOTSBHOMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  37
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  137
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Trp-PheOtBu 、 4-[2-tert-butoxycarbonylamino-3-carboxy-3-(4-methoxybenzylsulfanyl)propyl]benzoic acid tert-butyl ester 在 1-羟基苯并三唑 、 1-[3-(dimethylamino)-propyl]-3-ethylcarbodiimide methiodide 、 N,N-二异丙基乙胺 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 48.0h， 生成
  参考文献：
  名称：

  Type b botulism toxin inhibitors

  摘要：

  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。

  公开号：

  US20040176333A1
• 作为产物：
  描述：

  N,4-bis[(1,1-dimethylethoxy)carbonyl]-L-Phe 在 N-甲基吗啉 、 正丁基锂 、 六甲基二硅氮烷 、 三丁基氧化锡 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 、 乙腈 为溶剂， 反应 126.5h， 生成 4-[2-tert-butoxycarbonylamino-3-carboxy-3-(4-methoxybenzylsulfanyl)propyl]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

• US7205435B2
  申请人：——

  公开号：US7205435B2

  公开（公告）日：2007-04-17
• 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.
• 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。