- Probing the effects of pyrimidine functional group switches on acyclic fleximer analogues for antiviral activity
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Due to their ability to inhibit viral DNA or RNA replication, nucleoside analogues have been used for decades as potent antiviral therapeutics. However, one of the major limitations of nucleoside analogues is the development of antiviral resistance. In that regard, flexible nucleoside analogues known as “fleximers” have garnered attention over the years due to their ability to survey different amino acids in enzyme binding sites, thus overcoming the potential development of antiviral resistance. Acyclic fleximers have previously demonstrated antiviral activity against numerous viruses including Middle East Respiratory Syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), and, most recently, flaviviruses such as Dengue (DENV) and Yellow Fever Virus (YFV). Due to these interesting results, a Structure Activity Relationship (SAR) study was pursued in order to analyze the effect of the pyrimidine functional group and acyl protecting group on antiviral activity, cytotoxicity, and conformation. The results of those studies are presented herein.
- Yates, Mary K.,Chatterjee, Payel,Flint, Mike,Arefeayne, Yafet,Makuc, Damjan,Plavec, Janez,Spiropoulou, Christina F.,Seley-Radtke, Katherine L.
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- Identification of highly efficacious glucocorticoid receptor agonists with a potential for reduced clinical bone side effects
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Synthesis and structure-activity relationship (SAR) of a series of nonsteroidal glucocorticoid receptor (GR) agonists are described. These compounds contain "diazaindole" moieties and display different transcriptional regulatory profiles in vitro and are
- Harcken, Christian,Riether, Doris,Kuzmich, Daniel,Liu, Pingrong,Betageri, Raj,Ralph, Mark,Emmanuel, Michel,Reeves, Jonathan T.,Berry, Angela,Souza, Donald,Nelson, Richard M.,Kukulka, Alison,Fadra, Tazmeen N.,Zuvela-Jelaska, Ljiljana,Dinallo, Roger,Bentzien, J?rg,Nabozny, Gerald H.,Thomson, David S.
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p. 1583 - 1598
(2014/03/21)
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- Synthetic routes to a series of proximal and distal 2′-deoxy fleximers
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Two series of innovative 2-deoxy nucleoside analogues have been designed where the nucleobase has been split into its imidazole and pyrimidine subunits. This structural modification serves to introduce flexibility into the nucleobase scaffold while still
- Wauchope, Orrette R.,Velasquez, Melvin,Seley-Radtke, Katherine
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p. 3496 - 3504
(2013/01/15)
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- 1,1,1-TRIFLUORO-4-PHENYL-4-METHYL-2-(1H-PYRROLO
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Compounds of Formula (IA), IB), IC), and (ID) wherein R1, R2, R3, R4, R5, and R6 are as respectively defined herein for Formula (IA), (IB), (IC), and (ID), or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.
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Page/Page column 177
(2010/02/11)
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- SUBSTITUTED (AMINOIMINOMETHYL OR AMINOMETHYL) BENZOHETEROARYL COMPOUNDS
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This invention is directed to an (aminoiminomethyl or aminomethyl) benzoheteroaryl compound of formula I which is useful for inhibiting the activity of Factor Xa by combining said compound with a composition containing Factor Xa. The present invention is also directed to compositions containing compounds of the formula I, methods for their preparation, their use, such as in inhibiting the formation of thrombin or for treating a patient suffering from, or subject to, a disease state associated with a physiologically detrimental excess amount of thrombin.
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- IODINATION OF SOME DIAZINES AND DIAZINE N-OXIDES
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A number of monosubstituted pyrazines, pyrimidines, and their N-oxides having the electron-donating amino groups were successfully iodinated.Depending on the reaction conditions, the 3-substituted pyrazine 1-oxides having a bulky dialkylamino group yielded the 6-iodo and 2,6-diiodopyrazine N-oxide derivatives together with some deoxygenated products.The mechanism with supportive evidence was presented to account for these chemical transformations.
- Jovanovic, Misa V.
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p. 1195 - 1210
(2007/10/02)
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