- Rapid syntheses of either enantiomer of important carbocyclic nucleoside precursors
-
The syntheses of both enantiomers of aminocyclopentanetriol 1, a versatile carbocyclic nucleoside precursor, is reported utilizing an amino acid-derived acylnitroso Diels-Alder cycloaddition. The sequence is practical and proceeds in an overall yield of 36% from the D-alanine-derived hydroxamic acid. (C) 2000 Elsevier Science Ltd.
- Shireman,Miller
-
-
Read Online
- A protected form of (1S,2R,3S,4R)-4-aminocyclopentane-1,2,3-triol, a useful precursor to 5′-nor carbocyclic nucleosides
-
5′-Nor carbocyclic nucleosides have been found to possess a variety of meaningful biological properties. One of the building blocks for this class of compounds is (1S,2R,3S,4R)-4-aminocyclopentane-1,2,3-triol. To date, the reported routes to this compound are not particularly facile. Thus, a convenient route to this triol in its protected isopropylidene form (2) from (+)-(1R,4S)-4-hydroxy-2-cyclopenten-1-yl acetate. This will facilitate the preparation of new 5′-nor carbocyclic nucleosides in the "D-ribo-like" configuration. This method is also adaptable to the "L-like" series and the 2′- and 3′-deoxy analogs.
- Rajappan,Hegde,Schneller
-
-
Read Online
- Method for preparing ticagrelor key intermediate
-
The invention relates to a chemical synthesis method of ticagrelor key intermediate 2-[[(3aR, 4S, 6R, 6aS)-6-aminotetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxolane-4-yl] oxy]ethanol (a key intermediate A). The method comprises the following steps: taking D-ribose as a raw material, and carrying out ten chemical reaction steps of 1-locus methylation and 2,3-loci isopropylidene protection, 4-locus derivatization, iodination, furan ring-opening, hydroxylamine reaction, palladium on carbon catalytic hydrogenation, amino Cbz protection, hydroxy protection, sodium borohydride reduction ester, Cbz removal protection and the like, thereby obtaining the key intermediate A. The raw materials are cheap and readily available, the preparation process is high in operability, steps of optical resolution, chiral induction and the like are avoided, the total yield is relatively high, and the product quality is better; particularly due to the use of sodium borohydride reduction ester, the preparation cost of ticagrelor is greatly reduced; and the method is suitable for large-scale industrial production.
- -
-
-
- Substituted pyridine and pyrimidine derivatives and their use in treating viral infections
-
The present invention provides compounds of Formula (I): and tautomers, isomers, and esters of said compounds, and pharmaceutically acceptable salts, solvates, and prodrugs of said compounds, wherein each of R, R1, X, Y, Z, R2, R3, R4, R5, R6, R7, R8, R9, R18, R19 and n is selected independently and as defined herein. Compositions comprising such compounds are also provided. The compounds of the invention are effective as inhibitors of HCV, and are useful, alone and together with other therapeutic agents, in treating or preventing diseases or disorders such as viral infections and virus-related disorders.
- -
-
Page/Page column 186; 187; 188
(2016/09/26)
-
- Synthesis method of ticagrelor intermediate
-
The present invention belongs to the field of chemical synthesis, and in particular relates to a synthesis method of a ticagrelor key intermediate. A chemical synthesis method of ticagrelor key intermediate 2-[(3aR,4S,6R,6aS)-6- amino tetrahydro-2,2-dimethyl-4H-cyclopenta-1,3- dioxolane-4-yl] oxy] ethanol is specially designed. The method uses (1R,4S)-4 (benzyloxy)-2-alkenyl cyclopentanecarboxylic acid as a starting material, and conducts the steps of amidation, olefin oxidation, cyclization, Hoffmann reaction, deprotection and etherification to obtain an object compound. The method has the advantages of cheap and available raw materials, simple process, easily operated reaction process and high yield, and is applicable for industrial mass production.
- -
-
Paragraph 0010; 0027; 0028
(2016/10/10)
-
- SYNTHESIS OF TRIAZOLOPYRIMIDINE COMPOUNDS
-
The present invention relates to the field of organic synthesis and describes the synthesis of specific intermediates suitable for the preparation of triazolopyrimidine compounds such as ticagrelor.
- -
-
Page/Page column 52
(2013/07/05)
-
- Synthesis of Aminocyclopentanetriol Derivatives
-
The present invention relates to the field of organic synthesis and describes the synthesis of specific intermediates suitable for the preparation of triazolopyrimidine compounds such as ticagrelor. The present invention provides in particular a process for the preparation of a compound of formula V comprising: a) providing a compound of formula IV , and b) reducing the compound of formula IV with activated zinc in the presence of copper to give the compound of formula V.
- -
-
Paragraph 0079; 0080
(2014/01/07)
-
- IMPROVED PROCESSES FOR PREPARING PURE (3AR,4S,6R,6AS)-6-AMINO-2,2-DIMETHYLTETRAHDRO-3AH-CYCLOPENTA[D] [1,3]-DIOXOL-4-OL AND ITS KEY STARTING MATERIAL
-
Provided herein is an improved, commercially viable and industrially advantageous process for the preparation of a ticagrelor intermediate, (3aR,4S,6R,6aS)-6-amino-2,2- dimethyltetrahydro-3aH-cyclopenta[d][l,3]-dioxol-4-ol, which is useful for preparing ticagrelor or a pharmaceutically acceptable salt thereof in high yield and purity. The present invention further relates to an improved process for the preparation of (lS,4R)-cis-4-acetoxy- 2-cyclopenten-l-ol, which is a key starting material in the preparation of the ticagrelor intermediate.
- -
-
Page/Page column 22-23
(2012/05/31)
-
- A PROCESS FOR THE PREPARATION OF BENZYL [(3AS,4R,6S,6AR)-6-HYDROXY-2,2- DIMETHYLTETRAHYDRO-3AH-CYCLOPENTA[D][1,3]DIOXOL]-4-YL]CARBAMATE AND INTERMEDIATES IN THE PROCESS
-
The present invention is directed to a process for the preparation of benzyl [(3a S,4R,6S,6a R)-6-hydroxy-2,2-dimethyltetrahydro-3a H-cyclopenta[d][1,3]dioxol-4- yl]carbamate (VI), (VI), to products of said process and the use thereof.
- -
-
Page/Page column 8
(2012/12/13)
-
- Synthesis and biological evaluation of ticagrelor derivatives as novel antiplatelet agents
-
Ticagrelor (1) is the first reversible P2Y12 receptor antagonist blocking adenine diphosphate (ADP)-induced platelet aggregation with rapid onset and offset of effects. In this study, synthesis of ticagrelor and its derivatives has been accomplished in a convergent way. The compound design was based on modifications of ticagrelor and its major metabolite (33) in order to ameliorate their pharmacokinetic properties and dosing profile. The final compounds (1a-g, 35a-g) were evaluated for their inhibitory effect on ADP-induced platelet aggregation in rats. The assay results showed that some compounds (e.g., 1b, 1d, 33, 35b, 35f) exhibited comparable potency with that of ticagrelor.
- Zhang, Hao,Liu, Jun,Zhang, Luyong,Kong, Lingyi,Yao, Hequan,Sun, Hongbin
-
p. 3598 - 3602
(2012/07/14)
-
- CYCLOPROPYL MODULATORS OF P2Y12 RECEPTOR
-
The present invention relates to new cyclopropyl modulators of P2Y12 receptor activity, pharmaceutical compositions thereof, and methods of use thereof.
- -
-
Page/Page column 37
(2011/02/24)
-
- SUBSTITUTED PYRIDINE AND PYRIMIDINE DERIVATIVES AND THEIR USE IN TREATING VIRAL INFECTIONS
-
The present invention provides compounds of Formula (I): and tautomers, isomers, and esters of said compounds, and pharmaceutically acceptable salts, solvates, and prodrugs of said compounds, wherein wherein each of R, R1, X, Y, Z, R2, R3, R4, R5, R6, R7, R8, R9, R18, R19 and n is selected independently and as defined herein. Compositions comprising such compounds are also provided. The compounds of the invention are effective as inhibitors of HCV, and are useful, alone and together with other therapeutic agents, in treating or preventing diseases or disorders such as viral infections and virus-related disorders.
- -
-
Page/Page column 209
(2010/04/03)
-
- From ATP to AZD6140: The discovery of an orally active reversible P2Y12 receptor antagonist for the prevention of thrombosis
-
Starting from adenosine triphosphate (ATP), the identification of a novel series of P2Y12 receptor antagonists and exploitation of their SAR is described. Modifications of the acidic side chain and the purine core and investigation of hydrophobic substituents led to a series of neutral molecules. The leading compound, 17 (AZD6140), is currently in a large phase III clinical trial for the treatment of acute coronary syndromes and prevention of thromboembolic clinical sequelae.
- Springthorpe, Brian,Bailey, Andrew,Barton, Patrick,Birkinshaw, Timothy N.,Bonnert, Roger V.,Brown, Roger C.,Chapman, David,Dixon, John,Guile, Simon D.,Humphries, Robert G.,Hunt, Simon F.,Ince, Francis,Ingall, Anthony H.,Kirk, Ian P.,Leeson, Paul D.,Leff, Paul,Lewis, Richard J.,Martin, Barrie P.,McGinnity, Dermot F.,Mortimore, Michael P.,Paine, Stuart W.,Pairaudeau, Garry,Patel, Anil,Rigby, Aaron J.,Riley, Robert J.,Teobald, Barry J.,Tomlinson, Wendy,Webborn, Peter J.H.,Willis, Paul A.
-
p. 6013 - 6018
(2008/04/02)
-
- An improved approach to chiral cyclopentenone building blocks. Total synthesis of pentenomycin I and neplanocin A
-
An improved approach to enantiomerically pure hydroxylated cyclopentenones is reported here, which involves intramolecular nitrone cycloaddition of sugar-derived chiral pent-4-enals and hex-5-en-ones-2 followed by N-O bond cleavage, quaternization of the amine thus produced, and finally oxidative elimination of the amino group. Synthesis of pentenomycin I and neplanocin A is described following this methodology.
- Gallos, John K.,Stathakis, Christos I.,Kotoulas, Stefanos S.,Koumbis, Alexandros E.
-
p. 6884 - 6890
(2007/10/03)
-
- L-deaza-5'-noraisteromycin.
-
(+/-)-1-Deazaaristeromycin (4) has been reported to be an inactivator of S-adenosylhomocysteine (AdoHcy) hydrolase and, as a consequence, to affect S-adenosylmethionine (AdoMet) mediated macromolecular biomethylations. To extend this to our program focused on 5'-noraristeromycin derivatives as inhibitors of the same hydrolase enzyme as potential antiviral agents, both enantiomers of 1-deaza-5'-noraristeromycin (5 and 20) have been prepared. Compounds 5 and 20 were evaluated against the following viruses: vaccinia, cowpox, monkeypox, Ebola, herpes simplex type 1 and 2, human cytomegalovirus, Epstein Barr, varicella zoster, hepatitis B, hepatitis C, HIV-1 and HIV-2, adenovirus type 1, measles, Pichinde, parainfluenza type 3, influenza A (H1N1 and H3N2), influenza B, Venezuelan equine encephalitis, rhinovirus type 2, respiratory syncytial, yellow fever, and West Nile. No activity was found nor was there any cytotoxicity to the viral host cells.
- Yin, Xueqiang,Schneller, Stewart W
-
-
- Synthesis and transformations of (1R,2R,3S,4R)-4-O-benzylhydroxylamino-2,3-O- isopropylidene-1,2,3-cyclopentanetriol: Synthesis of (1S,2R,3S,4R)-4-amino-2,3-O-isopropylidene-1,2,3- cyclopentanetriol
-
The synthesis and some new transformations of (1R,2R,3S,4R)-4-O-benzylhydroxylamino-2,3-O-isopropylidene-1,2,3 -cyclopentanetriol are described. Particularly relevant is the synthesis of (1S,2R,3S,4R)-4-amino-2,3-O-isopropylide-1,2,3-cyclopentanetriol 7 from D-ribonolactone, via intermediate 1, in eight steps and 12% overall yield.
- Marco-Contelles, Jose,Rodriguez-Fernandez, Ma. Mercedes
-
p. 2249 - 2256
(2007/10/03)
-
- Expeditoious Synthesis of Aminocyclopentitols from D-Ribose via Intramolecular Nitrone Cycloaddition
-
The synthesis of 4α-aminocyclopentane-1α,2β,3β-triol (a key-intermediate in the preparation of carbocyclic nucleosides) and its N-substituted derivatives, has been achieved by the intarmolecular nitrone cycloadditions of a γ-unsaturated aldehyde, easily accessible from D-ribose, followed by reductive N-O bond cleavage in the resulting bicyclic oxazanes.
- Gallos, John K.,Goga, Efthymia G.,Koumbis, Alexandros E.
-
p. 613 - 614
(2007/10/02)
-
