(3R,5R)-7-[2-(4-fluoro-phenyl)-5-isopropyl-3-phenyl-4-phenylcarbamoylpyrrol-1-yl]-3,5-dihydroxy-N-hydroxyheptanamide | 1174332-81-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: (3R,5R)-7-[2-(4-fluoro-phenyl)-5-isopropyl-3-phenyl-4-phenylcarbamoylpyrrol-1-yl]-3,5-dihydroxy-N-hydroxyheptanamide
• 英文别名: (3R,5R)-7-[2-(4-Fluoro-phenyl)-5-isopropyl-3-phenyl-4-phenylcarbamoyl pyrrol-1-yl]-3,5-dihydroxy-N-hydroxyheptanamide；1-[(3R,5R)-3,5-dihydroxy-7-(hydroxyamino)-7-oxoheptyl]-5-(4-fluorophenyl)-N,4-diphenyl-2-propan-2-ylpyrrole-3-carboxamide
• CAS: 1174332-81-0
• 化学式: C₃₃H₃₆FN₃O₅
• 分子量: 573.664
• InChiKey: LCQMZRDBGJAUEU-KAYWLYCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  42
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  124
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  lipitor 在 盐酸 、 羟胺 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 为溶剂， 反应 50.5h， 生成 (3R,5R)-7-[2-(4-fluoro-phenyl)-5-isopropyl-3-phenyl-4-phenylcarbamoylpyrrol-1-yl]-3,5-dihydroxy-N-hydroxyheptanamide
  参考文献：
  名称：

  [EN] NOVEL CLASS OF COMPOUNDS FOR THE TREATMENT OF CARDIOVASCULAR DISEASE
  [FR] NOUVELLE CLASSE DE COMPOSÉS DESTINÉS AU TRAITEMENT D'UNE MALADIE CARDIOVASCULAIRE

  摘要：

  本发明涉及医学领域，具体是心血管疾病的治疗和预防领域。

  公开号：

  WO2017137469A1

文献信息

• 3,5,N-TRIHYDROXY-ALKANAMIDE AND DERIVATIVES: METHOD FOR MAKING SAME AND USE THEREOF
  申请人：Academia Sinica

  公开号：US20150148360A1

  公开（公告）日：2015-05-28

  The present invention provides novel compounds of Formula (I), and pharmaceutically compositions thereof. Compounds of Formula (I) are inhibitors of histone deacetylases (HDACs) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR). Also provided are methods of using the compounds and pharmaceutical compositions for inhibiting the activity of HDACs and HMGR, treating diseases associated with HDACs or HMGR (e.g., cancer, hypercholesterolemia, an acute or chronic inflammatory disease, autoimmune disease, allergic disease, pathogen infection, neurodegenerative disease, and a disease associated with oxidative stress), or inhibiting drug resistance of cancer cells.

  本发明提供了公式（I）的新型化合物及其药物组合物。公式（I）的化合物是组蛋白去乙酰化酶（HDACs）和3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶（HMGR）的抑制剂。还提供了使用这些化合物和药物组合物的方法，用于抑制HDACs和HMGR的活性，治疗与HDACs或HMGR相关的疾病（例如癌症，高胆固醇血症，急性或慢性炎症性疾病，自身免疫疾病，过敏疾病，病原体感染，神经退行性疾病和与氧化应激相关的疾病），或抑制癌细胞的耐药性。
• 3,5,N-trihydroxy-alkanamide and derivatives: method for making same and use thereof
  申请人：Academia Sinica

  公开号：US09353061B2

  公开（公告）日：2016-05-31

  The present invention provides novel compounds of Formula (I), and pharmaceutically compositions thereof. Compounds of Formula (I) are inhibitors of histone deacetylases (HDACs) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR). Also provided are methods of using the compounds and pharmaceutical compositions for inhibiting the activity of HDACs and HMGR, treating diseases associated with HDACs or HMGR (e.g., cancer, hypercholesterolemia, an acute or chronic inflammatory disease, autoimmune disease, allergic disease, pathogen infection, neurodegenerative disease, and a disease associated with oxidative stress), or inhibiting drug resistance of cancer cells.

  本发明提供了式（I）的新型化合物及其药物组合物。式（I）的化合物是组蛋白去乙酰化酶（HDACs）和3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶（HMGR）的抑制剂。还提供了使用该化合物和药物组合物来抑制HDAC和HMGR的活性，治疗与HDAC或HMGR相关的疾病（例如癌症，高胆固醇血症，急性或慢性炎症性疾病，自身免疫疾病，过敏性疾病，病原体感染，神经退行性疾病和与氧化应激相关的疾病），或抑制癌细胞的耐药性的方法。
• Design and Synthesis of Dual-Action Inhibitors Targeting Histone Deacetylases and 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase for Cancer Treatment
  作者：Jhih-Bin Chen、Ting-Rong Chern、Tzu-Tang Wei、Ching-Chow Chen、Jung-Hsin Lin、Jim-Min Fang

  DOI：10.1021/jm400179b

  日期：2013.5.9

  A series of dual-action compounds were designed to target histone deacetylase (HDAC) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) by having a hydroxamate group essential for chelation with the zinc ion in the active site of HDAC and the key structural elements of statin for binding with both proteins. In our study, the statin hydroxamic acids prepared by a fused strategy are most promising in cancer treatments. These compounds showed potent inhibitory activities against HDACs and HMGR with IC50 values in the nanomolar range. These compounds also effectively reduced the HMGR activity as well as promoted the acetylations of histone and tubulin in cancer cells, but were not toxic to normal cells.
• [EN] 3,5,N-TRIHYDROXY-ALKANAMIDE AND DERIVATIVES: METHOD FOR MAKING SAME AND USE THEREOF<br/>[FR] 3,5,N-TRIHYDROXY-ALCANAMIDE ET LEURS DÉRIVÉS : PROCÉDÉ DE PRÉPARATION ET UTILISATION
  申请人：ACADEMIA SINICA

  公开号：WO2014015235A3

  公开（公告）日：2014-03-06
• NOVEL CLASS OF COMPOUNDS FOR THE TREATMENT OF CARDIOVASCULAR DISEASE
  申请人：STICHTING KATHOLIEKE UNIVERSITEIT

  公开号：US20190038588A1

  公开（公告）日：2019-02-07

  The present invention relates to the field of medicine, specifically the field of treatment and prevention of cardiovascular diseases.