(2R,4S,5S)-5-tert-Butoxycarbonylamino-4-hydroxy-2,7-dimethyl-octanoic acid | 881009-00-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (2R,4S,5S)-5-tert-Butoxycarbonylamino-4-hydroxy-2,7-dimethyl-octanoic acid
• 英文别名: (2R,4S,5S)-5-[[(1,1-Dimethylethoxy)carbonyl]amino]-4-hydroxy-2,7-dimethyloctanoic acid；(2R,4S,5S)-4-hydroxy-2,7-dimethyl-5-[(2-methylpropan-2-yl)oxycarbonylamino]octanoic acid
• CAS: 881009-00-3
• 化学式: C₁₅H₂₉NO₅
• 分子量: 303.399
• InChiKey: NWQFEDALCBRPNN-WOPDTQHZSA-N

物化性质

• 沸点：
  467.6±40.0 °C(Predicted)
• 密度：
  1.075±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  21.0
• 可旋转键数：
  7.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  95.86
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (2R,4S,5S)-5-tert-Butoxycarbonylamino-4-hydroxy-2,7-dimethyl-octanoic acid 在 咪唑 、 4-二甲氨基吡啶 、 碳酸氢钠 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.5h， 生成 (2R,4S,5S)-5-[(fluorenylmethyloxycarbonyl)amino]-4-[(tert-butyldimethylsilyl)oxy]-2,7-dimethyloctanoic acid
  参考文献：
  名称：

  人脑Memapsin 2（β-分泌酶）有效抑制剂的设计。

  摘要：

  DOI：

  10.1021/ja000300g
• 作为产物：
  描述：

  (S)-5-tert-Butoxycarbonylamino-4-hydroxy-7-methyl-octanoic acid ethyl ester 在 lithium hydroxide 、 溶剂黄146 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 水 、 甲苯 为溶剂， 反应 4.58h， 生成 (2R,4S,5S)-5-tert-Butoxycarbonylamino-4-hydroxy-2,7-dimethyl-octanoic acid
  参考文献：
  名称：

  含羟基乙烯二肽等排体的β-分泌酶抑制剂的合成

  摘要：

  摘要 近年来，具有 Leu*Ala 羟基乙烯二肽 (HED) 等排体的 β-分泌酶抑制剂一直是一个特别有趣的话题。本研究合成了模板化合物17，其P2'位置截断，P2和P3发生变化，与其他报道的强效抑制剂不同。目的是探索最佳反应条件并构建抑制剂库以研究理想的蛋白质-底物相互作用。

  DOI：

  10.1080/00397910600977509

文献信息

• BRAIN PERMEANT PEPTIDOMIMETIC BETA-SECRETASE 1 INHIBITORS FOR THE TREATMENT OR PROPHYLAXIS OF NEUROLOGICAL DISORDERS OR CONDITIONS
  申请人：IBET - INSTITUTO DE BIOLOGIA EXPERIMENTAL E TECNOLOGICA

  公开号：US20170296618A1

  公开（公告）日：2017-10-19

  The present application presents novel peptidomimetic substituted hydroxyethylene compounds, which are inhibitors of beta amyloid cleavage enzyme, capable to permeate the brain and to achieve therapeutic concentrations in the target organ, the brain. These compounds are incorporated in pharmaceutical compositions and applied in the treatment or prophylaxis of neurological disorders or conditions and also other disorders or conditions including Down's syndrome and diabetes.

  这项申请提出了一种新型的肽类模拟替代羟基乙烯化合物，这些化合物是β淀粉样蛋白裂解酶的抑制剂，能够渗透到大脑并在目标器官大脑中达到治疗浓度。这些化合物被纳入药物组合物中，并应用于治疗或预防神经系统疾病或症状以及其他疾病或症状，包括唐氏综合征和糖尿病。
• [EN] BICYCLIC COMPOUNDS WHICH INHIBIT BETA-SECRETASE ACTIVITY AND METHODS OF USE THEREOF<br/>[FR] COMPOSES BICYCLIQUES INHIBANT L'ACTIVITE DE LA BETA-SECRETASE ET PROCEDES D'UTILISATION ASSOCIES
  申请人：ZAPAQ INC

  公开号：WO2006034277A1

  公开（公告）日：2006-03-30

  The present invention provides bicyclic beta-secretase inhibitors and methods for their use, including methods of treating of Alzheimer’s disease.

  本发明提供了双环β-分泌酶抑制剂及其用途，包括用于治疗阿尔茨海默病的方法。
• Structure-Based Design:  Potent Inhibitors of Human Brain Memapsin 2 (β-Secretase)
  作者：Arun K. Ghosh、Geoffrey Bilcer、Cynthia Harwood、Reiko Kawahama、Dongwoo Shin、Khaja Azhar Hussain、Lin Hong、Jeffrey A. Loy、Chan Nguyen、Gerald Koelsch、Jacques Ermolieff、Jordan Tang

  DOI：10.1021/jm0101803

  日期：2001.8.1

  Memapsin 2 (beta-secretase) is one of two proteases that cleave the beta-amyloid precursor protein (APP) to produce the 40-42 residue amyloid-beta peptide (Abeta) in the human brain, a key event in the progression of Alzheimer's disease. On the basis of the X-ray crystal structure of our lead inhibitor (2, OM99-2 with eight residues) bound to memapsin, we have reduced the molecular weight and designed

  Memapsin 2（beta-secretase）是两种蛋白酶，它们会切割β-淀粉样蛋白前体蛋白（APP）在人脑中产生40-42个残基的淀粉样β-肽（Abeta），这是阿尔茨海默氏病进展的关键事件疾病。基于我们的铅抑制剂（2个，带有八个残基的OM99-2，具有8个残基）的X射线晶体结构，我们降低了分子量，并设计了有效的Memapsin抑制剂。已经提出了基于结构的设计和初步的结构活性研究。
• Amino-Containing Compounds Which Inhibit Memapsin 2 Beta-Secretase Activity and Methods of Use Thereof
  申请人：Ghosh Arun K.

  公开号：US20080125467A1

  公开（公告）日：2008-05-29

  The present invention provides novel beta-secretase inhibitors and methods for their use, including methods of treating of Alzheimer's disease.

  本发明提供了新型β-分泌酶抑制剂及其使用方法，包括治疗阿尔茨海默病的方法。
• Synthesis and preliminary evaluation of peptidomimetic inhibitors of human β-secretase
  作者：Yan Niu、Yuehua Wang、Xiaomin Zou、Xiaoming Yang、Chao Ma、Yang Lü、Bo Zhou、Yue Yuan、Guanhua Du、Ping Xu

  DOI：10.1016/j.ejmech.2010.01.044

  日期：2010.5

  Based on the structure of OM99-2 and the X-ray crystal structure of its complex with beta-secretase, a series of compounds containing the Leu*Ala hydroxyethylene isostere as a scissile bond substitution were designed. 31 compounds were synthesized and their beta-secretase inhibition activities were measured. It was found that isobutyl group was a better R(3) substitution as C-terminus in our target compounds, and 4-nitrobenzyl group was the best R(2) side chain. With the aid of molecular modeling, the binding modes of compounds 9 and 22 with beta-secretase were compared. The result revealed a stronger bonding mode of 22 than 9. This explored that the optimal length of this series of peptidomimetic inhibitors was P3-P2'. The molecular weights of compounds with this length are around 600. (C) 2010 Elsevier Masson SAS. All rights reserved.