(S)-2-[(Biphenyl-4-sulfonyl)-isopropoxy-amino]-N-hydroxy-3-methyl-butyramide | 849773-64-4

• 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: (S)-2-[(Biphenyl-4-sulfonyl)-isopropoxy-amino]-N-hydroxy-3-methyl-butyramide
• 英文别名: (2S)-N-hydroxy-3-methyl-2-[(4-phenylphenyl)sulfonyl-propan-2-yloxyamino]butanamide
• CAS: 849773-64-4
• 化学式: C₂₀H₂₆N₂O₅S
• 分子量: 406.503
• InChiKey: DGZZVIWCMGVHGV-IBGZPJMESA-N

物化性质

• 熔点：
  117-119 °C
• 密度：
  1.230±0.06 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：>20mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 危险品运输编号：
  UN 2811 6.1/PG 3
• 危险标志：
  GHS06
• 危险性描述：
  H301
• 危险性防范说明：
  P301 + P310

反应信息

• 作为产物：
  描述：

  (R)-tert-butyl 2-bromo-3-methylbutanoate 在 四丁基硫酸氢铵 、 caesium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 101.0h， 生成 (S)-2-[(Biphenyl-4-sulfonyl)-isopropoxy-amino]-N-hydroxy-3-methyl-butyramide
  参考文献：
  名称：

  N-i-Propoxy-N-biphenylsulfonylaminobutylhydroxamic acids as potent and selective inhibitors of MMP-2 and MT1-MMP

  摘要：

  Structural manipulation of the pharmacophoric model of type A selective MMP inhibitors (MMPi), obtained by the insertion of some alkyl substituents R-2 possessing an appropriate geometry, steric bulkiness and lipophilicity, is able to improve potency, in the subnanomolar range on MMP-2, and to give a good MMP inhibition on MMP-14 (MT1-MMP) in the designed MMPi of type C, while maintaining a good MMP-1/MMP-2 selectivity profile. The simultaneous inhibition of these two enzymes yields type C compounds, which are potent antiangiogenic agents, able to block a chemoinvasion model on HUVEC cells in the micromolar range. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.024

文献信息

• Methods for treating diseases related to mitochondrial stress
  申请人：712 NORTH, INC.

  公开号：US10906931B2

  公开（公告）日：2021-02-02

  Means and methods for therapeutic intervention of mitochondrial disorders or diseases, and in particular to a method for the treatment, prevention and/or amelioration of a disorder or disease correlated with mitochondrial stress or dysfunction, a mitochondrial disorder or disease, or a disorder or disease characterized by OPA1 alterations are disclosed. Thereby, a pharmaceutically active amount of a compound capable of modulating the activity of OMA1 and/or an oligomeric complex comprising OMA1 is administered to a patient in need of medical intervention. Methods of screening for a compound capable of modulating the activity of OMA1 and/or an oligomeric complex comprising OMA1 are disclosed. Methods for determining the susceptibility for, predisposition for, or the presence of such a disorder or disease and whether a person in need will benefit from the therapeutic intervention, i.e. personalized medicine are also disclosed.

  本发明公开了治疗干预线粒体紊乱或疾病的手段和方法，特别是治疗、预防和/或改善与线粒体应激或功能障碍相关的紊乱或疾病、线粒体紊乱或疾病或以OPA1改变为特征的紊乱或疾病的方法。因此，能够调节 OMA1 和/或包含 OMA1 的低聚物复合物活性的化合物的药用活性量被施用给需要医疗干预的患者。本发明公开了筛选能够调节 OMA1 和/或包含 OMA1 的低聚物复合物活性的化合物的方法。此外，还公开了用于确定此类失调或疾病的易感性、易患性或存在性，以及有需要的人是否将从治疗干预（即个性化医疗）中获益的方法。
• N-i-Propoxy-N-biphenylsulfonylaminobutylhydroxamic acids as potent and selective inhibitors of MMP-2 and MT1-MMP
  作者：Armando Rossello、Elisa Nuti、Paolo Carelli、Elisabetta Orlandini、Marco Macchia、Susanna Nencetti、Maurizio Zandomeneghi、Federica Balzano、Gloria Uccello Barretta、Adriana Albini、Roberto Benelli、Giovanni Cercignani、Gillian Murphy、Aldo Balsamo

  DOI：10.1016/j.bmcl.2005.01.024

  日期：2005.3

  Structural manipulation of the pharmacophoric model of type A selective MMP inhibitors (MMPi), obtained by the insertion of some alkyl substituents R-2 possessing an appropriate geometry, steric bulkiness and lipophilicity, is able to improve potency, in the subnanomolar range on MMP-2, and to give a good MMP inhibition on MMP-14 (MT1-MMP) in the designed MMPi of type C, while maintaining a good MMP-1/MMP-2 selectivity profile. The simultaneous inhibition of these two enzymes yields type C compounds, which are potent antiangiogenic agents, able to block a chemoinvasion model on HUVEC cells in the micromolar range. (c) 2005 Elsevier Ltd. All rights reserved.
• METHODS FOR TREATING DISEASES RELATED TO MITOCHONDRIAL STRESS
  申请人：Alavi Khorassani Moghadam, Marcel Victor

  公开号：EP3548039A1

  公开（公告）日：2019-10-09
• PYRANONE COMPOUNDS USEFUL TO MODULATE OMA1 PROTEASE
  申请人：712 North, Inc.

  公开号：US20210246125A1

  公开（公告）日：2021-08-12

  Pyranone compounds are disclosed herein, which were quite surprisingly found as having OMA1 and/or OPA1 modulatory properties. Compounds of present invention may provide useful for the treatment of certain conditions and diseases, which are amenable to OMA1 and/or OPA1-modulatory therapies. Such conditions may include conditions and diseases prevalent in the elderly, such as cancer and Alzheimer's disease. Pharmaceutical compositions comprising compounds of present invention may be combined with other treatments or further comprise other pharmaceutically active ingredients.
• [EN] METHODS FOR TREATING DISEASES RELATED TO MITOCHONDRIAL STRESS<br/>[FR] MÉTHODES DE TRAITEMENT DE MALADIES ASSOCIÉES AU STRESS MITOCHONDRIAL
  申请人：ALAVI KHORASSANI MOGHADAM MARCEL VICTOR

  公开号：WO2018102672A1

  公开（公告）日：2018-06-07

  Means and methods for therapeutic intervention of mitochondrial disorders or diseases, and in particular to a method for the treatment, prevention and/or amelioration of a disorder or disease correlated with mitochondrial stress or dysfunction, a mitochondrial disorder or disease, or a disorder or disease characterized by OPA1 alterations are disclosed. Thereby, a pharmaceutically active amount of a compound capable of modulating the activity of OMA1 and/or an oligomeric complex comprising OMA1 is administered to a patient in need of medical intervention. Methods of screening for a compound capable of modulating the activity of OMA1 and/or an oligomeric complex comprising OMA1 are disclosed. Methods for determining the susceptibility for, predisposition for, or the presence of such a disorder or disease and whether a person in need will benefit from the therapeutic intervention, i.e. personalized medicine are also disclosed.