- HMG-COA REDUCTASE DEGRADATION INDUCING COMPOUND
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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.
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- A compound targeting ubiquitination degradation HMGCR or a pharmaceutically acceptable salt thereof. Preparation method and application
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The invention relates to a compound of targeted ubiquitination degradation HMGCR or a pharmaceutically acceptable salt thereof as well as a preparation method and application thereof. The structure is shown in the general formula (I). The compound or the
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- Hydroxy methyl glutaryl coenzyme A reductase inhibitors
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The invention relates to a compound, in particular to an HMG-GoA reductase inhibitor. The HMG-GoA reductase inhibitor is ester formed by naphthol and Cn polyhydroxyalkanoate or Cn olefine acid of the compound in the formula I, wherein n is an integer from six to fourteen. The compound can be effectively used for treating or preventing dyslipidemia, for example, the compound can effectively treat or prevent hypercholesteremia or mixed type hyperlipidemia.
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- DUAL ACTION INHIBITORS AGAINST HISTONE DEACETYLASES AND 3-HYDROXY-3-METHYLGLUTARYL COENZYME A REDUCTASE
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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
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- Design and synthesis of dual-action inhibitors targeting histone deacetylases and 3-hydroxy-3-methylglutaryl coenzyme a reductase for cancer treatment
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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.
- Chen, Jhih-Bin,Chern, Ting-Rong,Wei, Tzu-Tang,Chen, Ching-Chow,Lin, Jung-Hsin,Fang, Jim-Min
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p. 3645 - 3655
(2013/06/27)
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- HYPOCHOLESTEROLEMIC, ANTI-INFLAMMATORY AND ANTIEPILEPTIC NEUROPROTECTIVE COMPOUND
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The present invention describes a compound of formula (I) its hydroxy acid form, the pharmaceutically acceptable salts of said hydroxy acid and pharmaceutically acceptable prodrugs and solvates of the compound and of its hydroxy acid form and, in particular, said compound, its hydroxy acid form, salts, etc. for use in the prevention of: neurodegenerative diseases, cognitive impairment, diseases associated with undesired oxidation, age-associated pathological processes and progeria, cardiovascular diseases such as atherosclerosis, atrial fibrillation, dyslipidemia, hypercholesterolemia, hyperlipidemia, and hypertriglyceridemia, inflammation or inflammatory processes, or epilepsy, epileptic seizures and convulsions.
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- Synthesis of deuterium-labeled simvastatin
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This study describes the synthesis of deuterium-labeled simvastatin. The stable isotope-labeled compound was prepared starting from lovastatin in nine steps with 9% overall yield.
- Tian, Lei,Tao, Jie,Chen, Liqin
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p. 625 - 628
(2011/12/03)
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- Process for Preparing Substantially Pure Simvastatin
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This invention relates to an improved process for preparing substantially pure simvastatin (I), chemically known as (1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-hydroxy-6-oxotetrahydro-2-H-pyran-2-yl]ethyl]-3 ,7-dimeth-yl-1,2,3,7,8,8a-Hexahydronaphthalen-1-yl2,2-dimethyl butanoate, which comprises of: a) treating lovastatin (II) with an alkali metal hydroxide in a chosen suitable alcoholic solvent followed by relactonization to obtain the diol lactone intermediate (III) in a single vessel. b) selective silylation of 4-hydroxy group of diol lactone intermediate (III) with a chosen suitable silylating reagent to obtain mono silylated intermediate diol lactone (IV). c) acylation of the mono silylated intermediate (IV) to form silylated simvastatin (V) Or optionally, preparing silylated simvastatin (V) starting from Lovastatin (II) without isolating diol lactone (III) and monosilylated diol lactone (IV) and d) finally, removal of the silyl protecting group on silylated simvastatin (V) followed by purification to provide substantially pure simvastatin (I).
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- Neuroprotective, hypocholesterolemic and antiepileptic compound
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The present invention describes a compound of formula (I) its hydroxy acid form, the pharmaceutically acceptable salts of said hydroxy acid and pharmaceutically acceptable prodrugs and solvates of the compound and of its hydroxy acid form and, in particular, said compound, its hydroxy acid form, salts, etc. for its use in the prevention of: neurodegenerative diseases, cognitive deterioration, diseases associated with undesired oxidation, age-associated pathological processes and progeria, epilepsy, epileptic seizures and convulsions, cardiovascular diseases such as atherosclerosis, atrial fibrillation, dyslipemia, hypercholesterolemia, hyperlipidemia, and hypertriglyceridemia, or fungal or viral infections.
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Page/Page column 13
(2010/11/03)
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- METHOD OF PREPARING STATINS INTERMEDIATES
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Provided is a method for preparing a simvastatin intermediate. The method includes hydrolysis of mevinolinic acid as a starting material, lactonization, and protection of a hydroxy group of a lactone ring. Therefore, process steps are reduced and the simvastatin intermediate is produced in high yield.
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Page 10-11; 8
(2008/06/13)
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- Transformations of cyclic nonaketides by Aspergillus terreus mutants blocked for lovastatin biosynthesis at the lovA and lovC genes
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Two mutants of Aspergillus terreus with either the lovC or lovA genes disrupted were examined for their ability to transform nonaketides into lovastatin 1, a cholesterol-lowering drug. The lovC disruptant was able to efficiently convert dihydromonacolin L 5 or monacolin J 9 into 1, and could also transform desmethylmonacolin J 15 into compactin 3. In contrast, the lovA mutant has an unexpectedly active β-oxidation system and gives only small amounts of 1 upon addition of the immediate precursor 9, with most of the added nonaketide being degraded to heptaketide 22. Similarly, the lovA mutant does not accumulate the polyketide synthase product 5 and rapidly degrades any 5 added as a precursor via two cycles of β-oxidation and hydroxylation at C-6 to give 20. The possible involvement of epoxides 21a and 21b in the biosynthesis of 1 was also examined, but their instability in fermentation media and fungal cells will require purified enzymes to establish their role.
- Sorensen, John L.,Auclair, Karine,Kennedy, Jonathan,Hutchinson, C. Richard,Vederas, John C.
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- 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 9. The synthesis and biological evaluation of novel simvastatin analogs
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Substitution of hydroxy and hydroxyalkyl functionality at C-7 of the hexahydronaphthalene nucleus of simvastatin has provided novel analogs. The synthetic strategy employed epoxidation or Lewis acid-catalyzed aldol reaction of the 8-keto silyl enol ether
- Hartman,Halczenko,Duggan,Imagire,Smith,Pitzenberger,Fitzpatrick,Alberts,Bostedor,Chao,Germershausen,Gilfillan,Hunt
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p. 3813 - 3821
(2007/10/02)
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- Macrocyclic lactone HMG-CoA reductase inhibitors
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Novel 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors which are useful as antihypercholesterolemic agents and are represented by the following general structural formula (I): STR1 are disclosed. Also disclosed are pharmaceutical compositions and methods of use of the compounds of formula (I).
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