methyl isobutyl-L-leucinate | 19648-72-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl isobutyl-L-leucinate
• 英文别名: N-Isobutyl-leucin-OMe；methyl (2S)-4-methyl-2-(2-methylpropylamino)pentanoate
• CAS: 19648-72-7
• 化学式: C₁₁H₂₃NO₂
• 分子量: 201.309
• InChiKey: CNBSZZZMBPTRNJ-JTQLQIEISA-N

物化性质

• 沸点：
  246.5±23.0 °C(Predicted)
• 密度：
  0.900±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  14
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl isobutyl-L-leucinate 在 dimethyl sulfide borane 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 58.17h， 生成
  参考文献：
  名称：

  Discovery of selective, orally bioavailable inhibitor of mouse chitotriosidase

  摘要：

  This article describes our work towards the identification of a potent and selective inhibitor of mouse chitotriosidase (mCHIT1). A series of small molecule inhibitors of mCHIT1 and mAMCase have been developed from early lead compound 1. Examination of synthetized analogues led to discovery of several novel highly potent compounds. Among them compound 9 (OAT-2068) displays a remarkable 143-fold mCHIT1 vs. mAMCase selectivity. To explain the observed SAR molecular docking experiments were performed, which were in line with the experimental data from the enzymatic assays. Inhibitor 9 (OAT-2068) was found to have an excellent pharmacokinetic profile. This, together with high activity and selectivity, makes the compound an ideal and unique tool for studying the role of CHIT1 in biological models. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.12.047

文献信息

• CYTOTOXIC PEPTIDES
  申请人：BIOMOLECULAR RESEARCH INSTITUTE LTD.

  公开号：EP0935608A1

  公开（公告）日：1999-08-18
• EP0935608A4
  申请人：——

  公开号：EP0935608A4

  公开（公告）日：2004-09-15
• [EN] CYTOTOXIC PEPTIDES<br/>[FR] PEPTIDES CYTOTOXIQUES
  申请人：——

  公开号：WO1998013377A1

  公开（公告）日：1998-04-02

  [EN] This invention relates to cytotoxic, myristylated peptides derived from the N-terminus of the Nef protein. The peptides preferably comprise a domain comprising a net positive charge and an alpha -helical region. The invention also relates to compounds which inhibit the cytotoxicity of the Nef protein, the methods of preventing Nef toxicity, HIV infection, and to pharmaceutical compositions comprising such compounds.
  [FR] La présente invention concerne des peptides cytotoxiques myristilés dérivés de la terminaison N de la protéine Nef. Ces peptides comprennent de préférence un domaine comportant une charge positive nette et une région d'hélice alpha . L'invention, qui concerne également des composés inhibiteurs de la cytotoxicité par la protéine Nef, des techniques de prévention de la toxicité par la Nef, de prévention de l'infection par le VIH, concerne enfin des compositions pharmaceutiques comprenant de tels composés.
• Discovery of selective, orally bioavailable inhibitor of mouse chitotriosidase
  作者：Marzena Mazur、Agnieszka Bartoszewicz、Barbara Dymek、Magdalena Salamon、Gleb Andryianau、Michał Kowalski、Sylwia Olejniczak、Krzysztof Matyszewski、Elżbieta Pluta、Bartłomiej Borek、Filip Stefaniak、Agnieszka Zagozdzon、Marcin Mazurkiewicz、Robert Koralewski、Wojciech Czestkowski、Michał Piotrowicz、Piotr Niedziejko、Mariusz M. Gruza、Karolina Dzwonek、Adam Golebiowski、Jakub Golab、Jacek Olczak

  DOI：10.1016/j.bmcl.2017.12.047

  日期：2018.2

  This article describes our work towards the identification of a potent and selective inhibitor of mouse chitotriosidase (mCHIT1). A series of small molecule inhibitors of mCHIT1 and mAMCase have been developed from early lead compound 1. Examination of synthetized analogues led to discovery of several novel highly potent compounds. Among them compound 9 (OAT-2068) displays a remarkable 143-fold mCHIT1 vs. mAMCase selectivity. To explain the observed SAR molecular docking experiments were performed, which were in line with the experimental data from the enzymatic assays. Inhibitor 9 (OAT-2068) was found to have an excellent pharmacokinetic profile. This, together with high activity and selectivity, makes the compound an ideal and unique tool for studying the role of CHIT1 in biological models. (C) 2017 Elsevier Ltd. All rights reserved.