(4R,6R)-6-(2-{(1S,2S,6R,8S,8aR)-8-[(p-nitrophenoxy)carbonyloxy]-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthyl}ethyl)-4-tert-butyldimethylsilyloxy-3,4,5,6-tetrahydro-2H-pyran-2-one | 1431473-49-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4R,6R)-6-(2-{(1S,2S,6R,8S,8aR)-8-[(p-nitrophenoxy)carbonyloxy]-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthyl}ethyl)-4-tert-butyldimethylsilyloxy-3,4,5,6-tetrahydro-2H-pyran-2-one
• 英文别名: [(1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-[tert-butyl(dimethyl)silyl]oxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] (4-nitrophenyl) carbonate
• CAS: 1431473-49-2
• 化学式: C₃₂H₄₅NO₈Si
• 分子量: 599.797
• InChiKey: ADIGGGGPDMYMLF-ZGVPWKSKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.76
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  117
• 氢给体数：
  0
• 氢受体数：
  8

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  4-(叔丁基二甲基甲硅烷氧基)-6-[2-(8-羟基-2,6-二甲基-1,2,6,7,8,8a-六氢萘)-乙基]-四氢吡喃-2-酮	(4R,6R)-6-[2-((1S,2S,6R,8S,8aR)-8-hydroxy-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthyl)ethyl]-4-[(tert-butyldimethylsilyl)oxy]-3,4,5,6-tetrahydro-2H-pyran-2-one	79902-31-1	C25H42O4Si	434.692
  洛伐他汀	lovastatin	75330-75-5	C24H36O5	404.547
  ——	lovastatin acid	——	C24H38O6	422.562
  莫那可林J	monacolin J	79952-42-4	C19H28O4	320.429

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	(4R,6R)-6-[2-((1S,2S,6R,8S,8aR)-8-{([7-(allyloxy)-7-oxoheptyl]carbamoyl)oxy}-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthyl)ethyl]-4-[(tert-butyldimethylsilyl)oxy]-3,4,5,6-tetrahydro-2H-pyran-2-one	1431473-57-2	C36H59NO7Si	645.952
  ——	(4R,6R)-6-(2-{(1 S,2S,6R,8S,8aR)-8-[(4-ethynylphenyl)carbamoyloxy]-2,6-di methyl-1,2,6,7,8,8a-hexahydronaphthyl}ethyl)-4-tert-butyldimethylsilyloxy-3,4,5,6-tetrahydro-2H-pyran-2-one	1431473-50-5	C34H47NO5Si	577.836
  ——	(4R,6R)-6-[2-((1S,2S,6R,8S,8aR)-8-{([7-(hydroxyamino)-7-oxoheptyl]carbamoyl)oxy}-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthyl)ethyl]-4-[(tert-butyldimethylsilyl)oxy]-3,4,5,6-tetrahydro-2H-pyran-2-one	1431473-58-3	C33H56N2O7Si	620.902
  ——	(4R,6R)-6-(2-{(1S,2S,6R,8S,8aR)-8-[(4-ethynylbenzyl)carbamoyloxy]-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthyl}ethyl)-4-tert-butyldimethylsilyloxy-3,4,5,6-tetrahydro-2H-pyran-2-one	1431473-51-6	C35H49NO5Si	591.863
  ——	7-[4-[4-[[(1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-[tert-butyl(dimethyl)silyl]oxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl]oxycarbonylamino]phenyl]triazol-1-yl]heptanoic acid	1431473-52-7	C41H60N4O7Si	749.035
  ——	7-[4-[4-[[[(1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-[tert-butyl(dimethyl)silyl]oxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl]oxycarbonylamino]methyl]phenyl]triazol-1-yl]heptanoic acid	1431473-53-8	C42H62N4O7Si	763.062
  ——	(4R,6R)-6-(2-{(1S,2S,6R,8S,8aR)-8-[(4-{1-[7-(hydroxyamino)-7-oxoheptyl]-1H-1,2,3-triazol-4-yl}phenyl)carbamoyloxy]-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthyl}ethyl)-4-tert-butyldimethylsilyloxy-3,4,5,6-tetrahydro-2H-pyran-2-one	1431473-54-9	C41H61N5O7Si	764.05
  ——	(4R,6R)-6-(2-{(1S,2S,6R,8S,8aR)-8-[(4-{ 1-[7-(hydroxyamino)-7-oxoheptyl]-1H-1,2,3-triazol-4-yl}benzyl)carbamoyloxy]-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthyl}ethyl)-4-tert-butyldimethylsilyloxy-3,4,5,6-tetrahydro-2H-pyran-2-one	1431473-55-0	C42H63N5O7Si	778.077

反应信息

• 作为反应物：
  描述：

  (4R,6R)-6-(2-{(1S,2S,6R,8S,8aR)-8-[(p-nitrophenoxy)carbonyloxy]-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthyl}ethyl)-4-tert-butyldimethylsilyloxy-3,4,5,6-tetrahydro-2H-pyran-2-one 在 4-二甲氨基吡啶 、 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 吡啶 、 水 、 叔丁醇 为溶剂， 反应 39.0h， 生成 7-[4-[4-[[(1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-[tert-butyl(dimethyl)silyl]oxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl]oxycarbonylamino]phenyl]triazol-1-yl]heptanoic acid
  参考文献：
  名称：

  DUAL ACTION INHIBITORS AGAINST HISTONE DEACETYLASES AND 3-HYDROXY-3-METHYLGLUTARYL COENZYME A REDUCTASE

  摘要：

  本文披露了式（I）的新化合物及其用途。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。还提供了使用式（I）的化合物抑制HDACs和HMGR活性、治疗与HDACs或HMGR相关的疾病（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、神经退行性疾病或与氧化应激相关的疾病）的方法。

  公开号：

  US20140206645A1
• 作为产物：
  描述：

  洛伐他汀 在 咪唑 、 盐酸 、 甲醇 、 4-二甲氨基吡啶 、 potassium hydroxide 作用下， 以 吡啶 、 二氯甲烷 、 水 为溶剂， 反应 33.0h， 生成 (4R,6R)-6-(2-{(1S,2S,6R,8S,8aR)-8-[(p-nitrophenoxy)carbonyloxy]-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthyl}ethyl)-4-tert-butyldimethylsilyloxy-3,4,5,6-tetrahydro-2H-pyran-2-one
  参考文献：
  名称：

  DUAL ACTION INHIBITORS AGAINST HISTONE DEACETYLASES AND 3-HYDROXY-3-METHYLGLUTARYL COENZYME A REDUCTASE

  摘要：

  本文披露了式（I）的新化合物及其用途。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。还提供了使用式（I）的化合物抑制HDACs和HMGR活性、治疗与HDACs或HMGR相关的疾病（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、神经退行性疾病或与氧化应激相关的疾病）的方法。

  公开号：

  US20140206645A1

文献信息

• [EN] HMG-COA REDUCTASE DEGRADATION INDUCING COMPOUND<br/>[FR] COMPOSÉ INDUISANT LA DÉGRADATION DE LA HMG-COA RÉDUCTASE
  申请人：UPPTHERA

  公开号：WO2021201577A1

  公开（公告）日：2021-10-07

  The present invention relates HMG-CoA reductase degradation inducing compounds. Specifically, the present invention relates a bifunctional compound in which a HMG-CoA reductase binding moiety and an E3 ubiquitin ligase-binding moiety are linked by a chemical linker. The present invention also relates a method for preparing the compounds, and a method for degradation of HMG-CoA reducatase using the compounds, as well as use for prevention or treatment of HMG-CoA reductase related diseases using the compounds.

  本发明涉及HMG-CoA还原酶降解诱导化合物。具体而言，本发明涉及一种双功能化合物，其中HMG-CoA还原酶结合基团和E3泛素连接酶结合基团通过化学连接剂连接。本发明还涉及一种制备这些化合物的方法，以及使用这些化合物降解HMG-CoA还原酶的方法，以及使用这些化合物预防或治疗与HMG-CoA还原酶相关疾病的方法。
• 靶向泛素化降解HMGCR的化合物或其可药用的盐、制备方法及用途
  申请人：中国药科大学

  公开号：CN113527273B

  公开（公告）日：2023-08-22

  本发明靶向泛素化降解HMGCR的化合物或其可药用的盐、制备方法及用途。结构如通式(I)所示。该化合物或其可药用的盐有效靶向降解体内的胆固醇合成限速酶HMGCR，改善现有他汀类药物诱导HMGCR代偿性累积的缺陷，可用于制备治疗高血脂、动脉粥样硬化等心血管疾病的药物，有望成为具有全新作用机制的调血脂分子。
• 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.
• DUAL ACTION INHIBITORS AGAINST HISTONE DEACETYLASES AND 3-HYDROXY-3-METHYLGLUTARYL COENZYME A REDUCTASE
  申请人：National Taiwan University

  公开号：US20140206645A1

  公开（公告）日：2014-07-24

  Disclosed herein are novel compounds of formula (I), and uses thereof. The 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 of Formula (I) 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, or a disease associated with oxidative stress,

  本文披露了式（I）的新化合物及其用途。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。还提供了使用式（I）的化合物抑制HDACs和HMGR活性、治疗与HDACs或HMGR相关的疾病（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、神经退行性疾病或与氧化应激相关的疾病）的方法。