4-((2-ethyl-4-oxo-3-phenethyl-3,4-dihydroquinazolin-6-yl)-methyl)-N-hydroxybenzamide | 1450618-62-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-((2-ethyl-4-oxo-3-phenethyl-3,4-dihydroquinazolin-6-yl)-methyl)-N-hydroxybenzamide
• 英文别名: 4-((2-ethyl-3,4-dihydro-4-oxo-3-phenethylquinazolin-6-yl)methyl)-N-hydroxybenzamide；4-[[2-ethyl-4-oxo-3-(2-phenylethyl)quinazolin-6-yl]methyl]-N-hydroxybenzamide
• CAS: 1450618-62-8
• 化学式: C₂₆H₂₅N₃O₃
• 分子量: 427.503
• InChiKey: VLBQAJZSHGGUBQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  82
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氨基-5-碘苯甲酸 在 吡啶 、 亚磷酸三苯酯 、 tris-(dibenzylideneacetone)dipalladium(0) 、 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 lithium hydroxide 、 tri tert-butylphosphoniumtetrafluoroborate 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 甲醇 、 二氯甲烷 为溶剂， 反应 31.92h， 生成 4-((2-ethyl-4-oxo-3-phenethyl-3,4-dihydroquinazolin-6-yl)-methyl)-N-hydroxybenzamide
  参考文献：
  名称：

  Quinazolin-4-one Derivatives as Selective Histone Deacetylase-6 Inhibitors for the Treatment of Alzheimer’s Disease

  摘要：

  Novel quinazolin-4-one derivatives containing a hydroxamic acid moiety were designed and synthesized. All compounds were subjected to histone deacetylase (HDAC) enzymatic assays to identify selective HDAC6 inhibitors with nanomolar IC50 values. (E)-3-(2-Ethyl-7-fluoro-4-oxo-3-phenethyl-3,4-dihydroquinazolin-6-yl)-N-hydroxyacrylamide, 4h, NHis the most potent HDAC6 inhibitor (IC50, 8 nM). In vitro, these compounds induced neurite outgrowth accompanied by growth-associated protein 43 expression, and they enhanced the synaptic activities of PC12 and SH-SY5Y neuronal cells without producing toxic or mitogenic effects. Several of the compounds dramatically increased nonhistone protein acetylation, specifically of g-tubulin. Some of the more potent HDAC6 inhibitors decreased zinc-mediated beta-amyloid aggregation in vitro. N-Hydroxy-3-(2-methyl-4-oxo-3-phenethyl-3,4-dihydroquinazolin-7-yl)-acrylarnide, 3f, the most promising drug candidate, selectively inhibits HDAC6 (IC50,29 nM), practically does not affect human ether-a-go-go-related membrane channel activity (IC50 >10 mu M) or cytochrome P450 activity (IC50 >63 mu M) in vitro, and significantly improves learning-based performances of mice with beta-amyloid-induced hippocampal lesions.

  DOI：

  10.1021/jm400564j

文献信息

• HISTONE DEACETYLASES (HDACS) INHIBITORS
  申请人：ANNJI PHARMACEUTICAL CO., LTD.

  公开号：US20130267542A1

  公开（公告）日：2013-10-10

  Histone deacetylases inhibitors (HDACIs) and compositions comprising the same are disclosed. Methods of treating diseases and conditions wherein inhibition of HDAC provides a benefit are also disclosed.

  揭示了组蛋白去乙酰化酶抑制剂（HDACIs）和包含其的组合物。还公开了通过抑制HDAC来获益的治疗疾病和病况的方法。
• METHODS AND COMPOUNDS FOR THE TREATMENT OF GENETIC DISEASE
  申请人：Design Therapeutics, Inc.

  公开号：US20210238226A1

  公开（公告）日：2021-08-05

  The present disclosure relates to compounds and methods for modulating the expression of dmpk, atxn1, atxn2, atxn3, cacna1a, atxn7, ppp2r2br tbp, htt, jph3r ar, or atn1 and treating diseases and conditions in which dmpk, atxn1, atxn2, atxn3, cacna1a, atxn1, ppp2r2b, tbp, htt, jph3, ar, or atn1 plays an active role. The compound can be a transcription modulator molecule having a first terminus, a second terminus, and oligomeric backbone, wherein: a) the first terminus comprises a DNA-binding moiety capable of noncovalently binding to a nucleotide repeat sequence CAG or CTG; b) the second terminus comprises a protein-binding moiety binding to a regulatory molecule that modulates an expression of a gene comprising the nucleotide repeat sequence CAG or CTG; and c) the oligomeric backbone comprising a linker between the first terminus and the second terminus.
• US9155739B2
  申请人：——

  公开号：US9155739B2

  公开（公告）日：2015-10-13
• US9387209B2
  申请人：——

  公开号：US9387209B2

  公开（公告）日：2016-07-12
• Quinazolin-4-one Derivatives as Selective Histone Deacetylase-6 Inhibitors for the Treatment of Alzheimer’s Disease
  作者：Chao-Wu Yu、Pei-Teh Chang、Ling-Wei Hsin、Ji-Wang Chern

  DOI：10.1021/jm400564j

  日期：2013.9.12

  Novel quinazolin-4-one derivatives containing a hydroxamic acid moiety were designed and synthesized. All compounds were subjected to histone deacetylase (HDAC) enzymatic assays to identify selective HDAC6 inhibitors with nanomolar IC50 values. (E)-3-(2-Ethyl-7-fluoro-4-oxo-3-phenethyl-3,4-dihydroquinazolin-6-yl)-N-hydroxyacrylamide, 4h, NHis the most potent HDAC6 inhibitor (IC50, 8 nM). In vitro, these compounds induced neurite outgrowth accompanied by growth-associated protein 43 expression, and they enhanced the synaptic activities of PC12 and SH-SY5Y neuronal cells without producing toxic or mitogenic effects. Several of the compounds dramatically increased nonhistone protein acetylation, specifically of g-tubulin. Some of the more potent HDAC6 inhibitors decreased zinc-mediated beta-amyloid aggregation in vitro. N-Hydroxy-3-(2-methyl-4-oxo-3-phenethyl-3,4-dihydroquinazolin-7-yl)-acrylarnide, 3f, the most promising drug candidate, selectively inhibits HDAC6 (IC50,29 nM), practically does not affect human ether-a-go-go-related membrane channel activity (IC50 >10 mu M) or cytochrome P450 activity (IC50 >63 mu M) in vitro, and significantly improves learning-based performances of mice with beta-amyloid-induced hippocampal lesions.