39939-07-6Relevant articles and documents
PCSK9 INHIBITORS AND METHODS OF USE THEREOF
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Page/Page column 145-146, (2020/07/31)
The invention relates to novel heteroaryl compounds and pharmaceutical preparations thereof. The invention further relates to methods of treating or preventing cardiovascular diseases, and methods treating sepsis or septic shock, using the novel heterocyclic compounds disclosed herein.
PCSK9 INHIBITORS AND METHODS OF USE THEREOF
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Page/Page column 146-147, (2020/07/31)
The invention relates to a novel inhibitor pharmacophore of PCSK9 and heteroaryl compounds that bind the PCSK9 protein.
Novel spirocyclic systems via multicomponent aza-Diels-Alder reaction
Llona-Minguez, Sabin,Throup, Adam,Steiner, Emilie,Lightowler, Molly,Van Der Haegen, Sandra,Homan, Evert,Eriksson, Lars,Stenmark, P?l,Jenmalm-Jensen, Annika,Helleday, Thomas
supporting information, p. 7758 - 7764 (2017/10/06)
Here we present a two-step diastereoselective methodology building on a multicomponent aza-Diels-Alder reaction. Using previously unexplored cyclic ketones, heterocyclic amines and cyclopentadiene derivatives, we obtained novel spiro-heterocyclic frameworks at the interphase between drug-like molecules and natural products.
N-O bond as a glycosidic-bond surrogate: Synthetic studies toward polyhydroxylated N-alkoxypiperidines
Malik, Ga?lle,Ferry, Angélique,Guinchard, Xavier,Cresteil, Thierry,Crich, David
supporting information, p. 2168 - 2179 (2013/03/29)
A series of novel polyhydroxylated N-alkoxypiperidines has been synthesized by ring-closing double reductive amination (DRA) of highly functionalized 1,5-dialdehydes with various hydroxylamines. The required saccharide-based dialdehydes were prepared efficiently from sodium cyclopentadienylide in seven steps. A two-step protocol has been developed for the DRA; it led, after deprotection, to isofagomine, 3-deoxyisofagomine, and numerous other N-alkoxy analogues. The barrier to inversion in these polyhydroxylated N-alkoxypiperidine derivatives was found by variable-temperature NMR methods to be approximately 15 kcal mol-1. With the exception of N-hydroxyisofagomine itself, none of the compounds prepared showed significant inhibitory activity against sweet almond β-glucosidase. Copyright
Cis,cis,cis,cis-1,2,3,4,5-Pentakis(hydroxymethyl)cyclopentane
Pujol, Adeline R.,Ratel-Ramond, Nicolas,Gourdon, André
, p. 9139 - 9144 (2013/09/24)
All-cis pentamethanolcyclopentane has been obtained in six steps by Diels-Alder condensation of maleic anhydride with (benzyloxymethyl)cyclopenta-2, 4-diene, reduction of the anhydride to a diol that was protected as the acetonide. Then, ozonolysis of the double bond, followed by reduction led to a cis-diol. Then successive deprotections of the three other methanol groups gave the cis,cis,cis,cis-1,2,3,4,5-pentakis(hydroxymethyl)cyclopentane.
The preparation of several 1,2,3,4,5-functionalized cyclopentane derivatives
Kelch, Andre S.,Jones, Peter G.,Dix, Ina,Hopf, Henning
supporting information, p. 1705 - 1712 (2013/10/22)
With the goal of eventually synthesizing [5]radialene (3), the still missing member of the parent radialene hydrocarbons, we have prepared the pentaacetates 21 and 31, the pentabromide 29 and the hexabromide 32. In principle these should be convertible by elimination reactions to the desired target molecule.
Asymmetric synthesis of polyhydroxylated N -alkoxypiperidines by ring-closing double reductive amination: Facile preparation of isofagomine and analogues
Malik, Gaelle,Guinchard, Xavier,Crich, David
supporting information; experimental part, p. 596 - 599 (2012/02/16)
A de novo synthesis of novel polyhydroxylated N-alkoxypiperidines based on the ring-closing double reductive amination of 1,5-dialdehydes, obtained by oxidative cleavage of cyclopentene derivatives, with O-substituted hydroxylamines is reported. Isofagomine was accessed by cleavage of the N-O bond of an N-alkoxypiperidine.
Synthesis of 2′,3′-modified carbocyclic L -nucleoside analogues
Jessel, Soenke,Meier, Chris
experimental part, p. 1702 - 1713 (2011/05/04)
New divergent approaches to 2′,3′-modified carbocyclic L-nucleoside analogues starting from enantiomerically pure (1R,2S)- or (1S,2R)-2-(benzyloxymethyl)cyclopent-3-enol are described. In the key step, stereochemically pure cyclopentanols were condensed with N3-protected thymine through a modified Mitsunobu protocol. Moreover, several routes to different cyclopentanol derivatives, to prepare carbocyclic L-2′,3′-didehydro- 2′,3′-dideoxynucleosides (L-d4N), L-2′,3′- dideoxynucleosides (L-ddN), and L-ribonucleosides are reported. Copyright
Synthesis of [13C4]Baraclude (entecavir)
Tran, Scott B.,Ekhato, Ihoezo V.,Rinehart, J. Kent
scheme or table, p. 485 - 489 (2010/07/04)
Entecavir, labeled as 1H-[13C4]purin-6(9H)-one, was prepared from commercially available [13C]guanidine HCl, 1 and diethyl [1,2,3-13C3]malonate, 2. The reagents were condensed together to give 2-amino-4,6-dichloro[2,4,5,6-13C 4]pyrimidine 3, which in turn was coupled to an optically active amino cyclopentanol derivative, 9. A further sequence of eight reaction steps completed the constructions of the purine ring system and the exocyclic olefin attachment on the cyclic pentyl portion, 18. The removal of the methoxide and benzyl protecting groups gave [13C4]entecavir, 20 in an overall yield of 6.8%. The chemical purity of the title compound was determined by HPLC to be 99.23%. The percent isotopic [13C4] abundance was found by mass spectral analysis to be 96.7%. No detectable level of the unlabeled entecavir was found by LC-MS analysis. Copyright
Cyclopentane-nucleobase coupling in the synthesis of carbocyclic L-nucleosides: Is a SN2-reaction an alternative to the mitsunobu-reaction?
Jessel,Hense,Meier
, p. 1181 - 1184 (2008/09/17)
Several carbocyclic L-nucleosides have been synthesized by coupling a cyclopentane-system with heterocycles according to a modified Mitsunobu-protocol. This reaction gave two regioisomers, the N1-alkylated product and an unwanted O2-product. A simple SN2-reaction has been investigated as an alternative for such couplings. Copyright Taylor & Francis Group, LLC.
