648414-59-9Relevant academic research and scientific papers
METTL3 MODULATORS
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Page/Page column 63-64, (2021/04/30)
Provided are compounds of Formula (I') or (II'), or pharmaceutically acceptable salts thereof, and methods for their use and production.
PCSK9 INHIBITORS AND METHODS OF USE THEREOF
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, (2020/07/31)
The invention relates to a novel inhibitor pharmacophore of PCSK9 and heteroaryl compounds that bind the PCSK9 protein.
PCSK9 INHIBITORS AND METHODS OF USE THEREOF
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, (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.
The synthesis of possible transition state analogue inhibitors of thymidine phosphorylase
Evans, Gary B.,Gainsford, Graeme J.,Schramm, Vern L.,Tyler, Peter C.
, p. 406 - 409 (2015/04/27)
The synthetically challenging SN2 transition state mimic for thymidine phosphorylase, along with its phosphonate analogue, were synthesised via a modified Corey-Link reaction in good overall yields and ensuring the correct stereochemical outcome.
Synthesis and biological evaluation of phosphoramidate prodrugs of two analogues of 2-deoxy-d-ribose-1-phosphate directed to the discovery of two carbasugars as new potential anti-HIV leads
Hamon, Nadège,Slusarczyk, Magdalena,Serpi, Michaela,Balzarini, Jan,McGuigan, Christopher
, p. 829 - 838 (2015/02/19)
2-Deoxy-α-d-ribose-1-phosphate is of great interest as it is involved in the biosynthesis and/or catabolic degradation of several nucleoside analogues of biological and therapeutic relevance. However due to the lack of a stabilising group at its 2-position, it is difficult to synthesize stable prodrugs of this compound. In order to overcome this lack of stability, the synthesis of carbasugar analogues of 2-deoxyribose-1-phosphate was envisioned. Herein the preparation of a series of prodrugs of two carbocyclic analogues of 2-deoxyribose-1-phosphate using the phosphoramidate ProTide technology, along with their biological evaluation against HIV and cancer cell proliferation, is reported.
Stereoselective synthesis of D - And L -carbocyclic nucleosides by enzymatically catalyzed kinetic resolution
Mahler, Miriam,Reichardt, Bastian,Hartjen, Philip,Van Lunzen, Jan,Meier, Chris
, p. 11046 - 11062 (2012/10/07)
An efficient synthesis of (S)- or (R)-3-(benzyloxy-methyl)-cyclopent-3-enol was developed by appling an enzyme-catalyzed kinetic-resolution approach. This procedure allowed the syntheses of the enantiomeric building blocks (S)- and (R)-cyclopentenol with high optical purity (>98a % ee). In contrast to previous approaches, the key advantage of this procedure is that the resolution is done on the level of enantiomers that only contain one stereogenic center. Owing to this feature, it was possible to chemically convert the enantiomers into each other. By using this route, the starting materials for the syntheses of carbocyclic D- and L-nucleoside analogues were readily accessible. 3a',4a'-Unsaturated D- or L-carbocyclic nucleosides were obtained from the condensation of various nucleobases with (S)- or (R)-cyclopentenol. Functionalization of the double bond in 3a'-deoxy-3a',4a'-didehydro-carba-D- thymidine led to a variety of new nucleoside analogues. By using the cycloSal approach, their corresponding phosphorylated metabolites were readily accessable. Moreover, a new synthetic route to carbocyclic 2a'-deoxy-nucleosides was developed, thereby leading to D- and L-carba-dT. D-Carba-dT was tested for antiviral activity against multidrug-resistance HIV-1 strain E2-2 and compared to the known antiviral agent d4T, as well as L-carba-dT. Whilst L-carba-dT was found to be inactive, its D-analogue showed remarkably high activity against the resistant virus and significantly better than that of d4T. However, against the wild-type virus strain NL4/3, d4T was found to be more-active than D-carba-dT. Fighting chance: Various carbocyclic D- and L-nucleosides were synthesized from cyclopentadiene by enzyme-catalyzed kinetic resolution with high optical purity. In contrast to its L-analogue, D-carba-dT was antivirally active against multidrug-resistant HI-viruses. Copyright
Properties of oligonucleotide with phenyl-substituted carbocyclic nucleoside analogs for the formation of duplex and triplex DNA
Nasr, Tamer,Taniguchi, Yosuke,Takaki, Tomoko,Okamura, Hidenori,Sasaki, Shigeki
, p. 841 - 860 (2013/02/23)
(1S,3S,4R)-1-Phenyl-1-thymidyl-3-hydroxy-4-hydroxymethylcyclopentane (10) and their analogs were synthesized, incorporated into the oligodeoxynucleotides, and their properties were evaluated for the formation of duplex and triplex DNA. The known chiral cyclopentanone derivative was converted into the corresponding ketimine sulfonamide derivative, which was subjected to a stereoselective PhLi addition. The formed sulfonamide was hydrolyzed to afford the primary amino group, on which the thymine moiety was built. The benzyl protecting groups were removed to form the nucleoside analog having a phenyl group and the thymine unit at the 1 position of a carbocyclic skeleton (10). In the estimation of the oligodeoxynucleotides incorporating 10 for duplex and triplex formation, the carbocyclic nucleoside analog 10 did not show the stabilizing effect for duplex formation; on the other hand, it stabilized the triplex. Therefore, the skeleton of the phenyl-substituted carbocyclic nucleoside analog 10 may be a platform for the formation of stable triplex DNA.
Divergent synthesis and biological evaluation of carbocyclic α-, iso- and 3′-epi-nucleosides and their lipophilic nucleotide prodrugs
Ludek, Olaf R.,Kraemer, Tobias,Balzarini, Jan,Meier, Chris
, p. 1313 - 1324 (2007/10/03)
A new divergent approach towards carbocyclic α-, iso- and 3′-epi-nucleosides starting from enantiomerically pure (1S,2R)-2-benzyloxymethylcyclopent-3-enol (5) is described. In the key step, isomeric cyclopentanols were condensed with a N3-protected pyrimi
New convergent synthesis of carbocyclic nucleoside analogues
Ludek, Olaf R.,Meier, Chris
, p. 2101 - 2109 (2007/10/03)
Two convergent approaches towards the synthesis of carbocyclic nucleoside analogs will be described. Both approaches start from the stereochemically pure cyclopentenol 8 that has been prepared enantioselectively from an alkylated cyclopentadiene. Using these approaches, carbocyclic analogues of dT, FdU and BVdU have been prepared. Moreover, the conversion into the cycloSalpronucleotide and the corresponding nucleotide will be presented for one example.
Synthesis of carbocyclic analogues of thymidine
Ludek,Meier
, p. 683 - 685 (2007/10/03)
A new route towards an enantiomerically pure carbocyclic 2′-deoxyribonucleoside precursor was developed. After coupling with a nucleobase the product is easily accessible for further modifications at the 3′-hydroxy group.
