- GlcNAc Conjugated Atorvastatin with Enhanced Water Solubility and Cellular Internalization
-
Targeting ligands facilitate cell specific drug delivery and improve pharmaceutical properties. Herein, we designed two ligand drug conjugates by conjugating GlcNAc (N-acetylglucosamine) with atorvastatin. These two conjugates, termed G-AT and G-K-AT, exhibited enhanced water solubility and cellular uptake. Moreover, both G-AT and G-K-AT were able to release atorvastatin and consequently achieve significant inhibition against 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase.
- Zhang, Xinfu,Chen, Xiaofang,Zhao, Weiyu,Zeng, Chunxi,Luo, Xiao,Li, Wenqing,Li, Bin,Jiang, Justin,Dong, Yizhou
-
-
Read Online
- Asymmetric Synthesis of Atorvastatin Calcium through Intramolecular Oxidative Oxygen-Nucleophilic Bromocyclization
-
The stereocontrolled synthesis of atorvastatin calcium starting from commercially available d-aspartic acid using an intramolecular oxidative oxygen-nucleophilic bromocyclization of a homoallylic tert-butyl carbonate is described. This strategy allows the formation of the chiral syn-1,3-diol moiety with the desired stereochemistry, and provides a functionalized bromomethyl group for the construction of the atorvastatin side-chain with high regio- and diastereoselectivity. This route is attractive as it represents an efficient and environmentally sensitive approach to the large-scale synthesis of statins and their analogues.
- Wu, Yan,Liu, Min-Jie,Huang, Hai-Qing,Huang, Guan-Xin,Xiong, Fang-Jun,Chen, Fen-Er
-
p. 3681 - 3688
(2017/07/22)
-
- Rapid Asymmetric Synthesis of Disubstituted Allenes by Coupling of Flow-Generated Diazo Compounds and Propargylated Amines
-
We report herein the asymmetric coupling of flow-generated unstabilized diazo compounds and propargylated amine derivatives, using a new pyridinebis(imidazoline) ligand, a copper catalyst and base. The reaction proceeds rapidly, generating chiral allenes in 10–20 minutes with high enantioselectivity (89–98 % de/ee), moderate yields and a wide functional group tolerance.
- Poh, Jian-Siang,Makai, Szabolcs,von Keutz, Timo,Tran, Duc N.,Battilocchio, Claudio,Pasau, Patrick,Ley, Steven V.
-
supporting information
p. 1864 - 1868
(2017/02/05)
-
- METHODS FOR PROVIDING INTERMEDIATES IN THE SYNTHESIS OF ATORVASTATIN.
-
The invention relates to the field of medicinal chemistry, In particular, it relates to methods for providing intermediates in the synthesis of Atorvastatin, a competitive inhibitor of HMG-Co A reductase. Provided is a process for providing a compound having a Formula (I) or a pharmaceutically acceptable salt, ester, amide or stereoisomer thereof, comprising reacting in a 4 component Ugi-reaction in a single reaction mixture the compounds of formula A, formula B, formula C and formula D.
- -
-
Page/Page column 22
(2016/08/23)
-
- Synthesis and evaluation of atorvastatin esters as prodrugs metabolically activated by human carboxylesterases
-
We synthesized 11 kinds of prodrug with an esterified carboxylic acid moiety of atorvastatin in moderate to high yields. We discovered that they underwent metabolic activation specifically by the human carboxylesterase 1 (CES1) isozyme. The results sugges
- Mizoi, Kenta,Takahashi, Masato,Haba, Masami,Hosokawa, Masakiyo
-
p. 921 - 923
(2016/05/24)
-
- LYMPH DIRECTING PRODRUGS
-
H:\dar\Interwoven\NRPortbl\DCC\DAR\8230712_1.doc-12/08/2015 Abstract The present invention relates to compounds and their uses, in particular, compounds in the form of prodrugs that promote transport of a pharmaceutical agent to the lymphatic system and subsequently enhance release of the parent drug.
- -
-
Page/Page column 80; 81
(2016/02/29)
-
- METHOD FOR THE PREPARATION OF ATORVASTATIN AND INTERMEDIATES USED THEREIN
-
The present invention relates to a novel method for preparing atorvastatin. According to the present invention, provided are a novel intermediate of the preparation of atorvastatin and a method of preparing large amounts of atorvastatin in a safe manner using the intermediate.
- -
-
Page/Page column 13
(2011/02/18)
-
- STATIN DERIVATIVES
-
Dinitrate statins having improved pharmacological activity are described. They can be employed for treating and/or preventing several diseases, in particular acute coronary syndromes, neurodegenerative disorders as well as for reducing cholesterol levels.
- -
-
Page/Page column 28
(2012/01/13)
-
- Nitric Oxide Releasing Prodrugs of Therapeutic Agents
-
The present invention relates to nitric oxide releasing prodrugs of known drugs or therapeutic agents which are represented herein as compounds of formula (I) wherein the drugs or therapeutic agents contain one or more functional groups independently sele
- -
-
Page/Page column 80
(2011/11/06)
-
- A novel strategy towards the atorvastatin lactone
-
We describe a novel strategy to the atorvastatin lactone based on a Paal-Knorr synthesis of pyrrole 24 by condensing diketone 23 with primary amine 22. The latter contains the syn-1,3-diol subunit and a benzyl ether function at the other end of the chain. This allowed for manipulations on the pyrrole ring via iodination at C2, metalation with t-BuLi and carboxylation. The obtained acid 26 could be converted via amide formation, debenzylation, oxidation and lactonization to atorvastatin lactone 6. The key building block, 2-((4R,6S)-6-(2-(benzyloxy)ethyl)-2,2-dimethyl-1,3-dioxan-4-yl)ethanamine (22) was obtained by two sequential asymmetric transfer hydrogenative carbonyl allylations according to Krische.
- Sawant, Pramod,Maier, Martin E.
-
experimental part
p. 9738 - 9744
(2011/02/25)
-
- METHOD FOR THE PREPARATION OF ATORVASTATIN AND INTERMEDIATES USED THEREIN
-
The present invention relates to a novel method for preparing atorvastatin. According to the present invention, provided are a novel intermediate of the preparation of atorvastatin and a method of preparing large amounts of atorvastatin in a safe manner using the intermediate.
- -
-
Page/Page column 28-29
(2009/09/05)
-
- Process for the production of atorvastatin calcium un amorphous form
-
A process for the production of amorphous atorvastatin calcium and stabilized, amorphous atorvastatin calcium is provided.
- -
-
Page/Page column 16
(2010/11/30)
-
- SYNTHESIS OF 3,5-DIHYDROXY-7-PYRROL-1-YL HEPTANOIC ACIDS
-
Atorvastatin and related 3,5-dihydroxy-7-pyrrol-1-yl heptanoic acids can be made by oxidation of a 3,5-dihydroxy-7-pyrrol-1-yl heptanol precursor from novel but readily accessible starting materials. Silylether-protected 7-amino-3,5-dihydroxy heptanoic acid esters undergo Paal Knorr reaction with 1,4-diketones to give valuable silylether-diprotected 3,5-dihydroxy-7-pyrrol-1-yl heptanoic acid ester intermediates for preparing atorvastatin. The Paal Knorr reaction of ketal-proctected 7-amino-3R, 5R-dihydroxy heptanoic acid esters with 4-fluoro-α-(2-methyl-1-oxopropyl-γ-oxo-N,β-diphenylbenzenebutanamide occurs in high yield with few side products when it is conducted in a low boiling point ether.
- -
-
-
