5-((3-(benzo[b]thiophene-2-carboxamido)benzyl)oxy)nicotinamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: 5-((3-(benzo[b]thiophene-2-carboxamido)benzyl)oxy)nicotinamide
• 英文别名: 5-[[3-(1-Benzothiophene-2-carbonylamino)phenyl]methoxy]pyridine-3-carboxamide；5-[[3-(1-benzothiophene-2-carbonylamino)phenyl]methoxy]pyridine-3-carboxamide
• 化学式: C₂₂H₁₇N₃O₃S
• 分子量: 403.461
• InChiKey: WFAJGPAMLQVQFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  123
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-羟基烟酸甲酯 在 sodium tetrahydroborate 、 nickel(II) chloride hexahydrate 、 氨 、 1-羟基苯并三唑 、 caesium carbonate 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 calcium chloride 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 55.0h， 生成 5-((3-(benzo[b]thiophene-2-carboxamido)benzyl)oxy)nicotinamide
  参考文献：
  名称：

  5-((3-Amidobenzyl)oxy)nicotinamides as Sirtuin 2 Inhibitors

  摘要：

  Derived from our previously reported human sirtuin 2 (SIRT2) inhibitors that were based on a 5-aminonaphthalen-1-yloxy nicotinamide core structure, 5-((3-amidobenzyl)oxy)-nicotinamides offered excellent activity against SIRT2 and high isozyme selectivity over SIRT1 and SIRT3. Selected compounds also exhibited generally favorable in vitro absorption, distribution, metabolism, and excretion properties. Kinetic studies revealed that a representative SIRT2 inhibitor acted competitively against both NAD+ and the peptide substrate, an inhibitory modality that was supported by our computational study. More importantly, two selected compounds exhibited significant protection against asynuclein aggregation-induced cytotoxicity in SH-SYSY cells. Therefore, 5((3-amidobenzypoxy)nicotinamides represent a new class of SIRT2 inhibitors that are attractive candidates for further lead optimization in our continued effort to explore selective inhibition of SIRT2 as a potential therapy for Parkinson's disease.

  DOI：

  10.1021/acs.jmedchem.5b01376

文献信息

• THERAPEUTIC COMPOUNDS
  申请人：REGENTS OF THE UNIVERSITY OF MINNESOTA

  公开号：US20160376238A1

  公开（公告）日：2016-12-29

  The invention provides compounds of formula (I): wherein, A, C, D, X, and Y have any of the values defined in the specification, and salts thereof. The compounds are SIRT2 inhibitors and are useful for treating SIRT2 associated conditions.

  这项发明提供了式（I）的化合物： 其中，A、C、D、X 和 Y 可以取规范中定义的任何值，以及它们的盐。这些化合物是SIRT2抑制剂，可用于治疗与SIRT2相关的疾病。
• US9951019B2
  申请人：——

  公开号：US9951019B2

  公开（公告）日：2018-04-24