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Your search keyword '"Kerekes, Angela D."' showing total 3 results
Start Over Author "Kerekes, Angela D." Journal bioorganic medicinal chemistry letters
3 results on '"Kerekes, Angela D."'

1. Discovery of a highly potent orally bioavailable imidazo-[1, 2-a]pyrazine Aurora inhibitor.

Author

Yu T, Zhang Y, Kerekes AD, Tagat JR, Doll RJ, Xiao Y, Esposite S, Hruza A, Belanger DB, Voss M, Rainka MP, Basso A, Liu M, Liang L, Sui N, Prelusky D, Rindgen D, and Zhang L

Subjects
Administration, Oral, Animals, Antineoplastic Agents administration & dosage, Antineoplastic Agents chemical synthesis, Antineoplastic Agents pharmacokinetics, Dogs, HCT116 Cells, Haplorhini, Histones metabolism, Humans, Imidazoles administration & dosage, Imidazoles chemical synthesis, Imidazoles pharmacokinetics, Mice, Phosphorylation, Protein Kinase Inhibitors administration & dosage, Protein Kinase Inhibitors chemical synthesis, Protein Kinase Inhibitors pharmacokinetics, Pyrazines administration & dosage, Pyrazines chemical synthesis, Pyrazines pharmacokinetics, Rats, Stereoisomerism, Xenograft Model Antitumor Assays, Antineoplastic Agents therapeutic use, Aurora Kinase A antagonists & inhibitors, Aurora Kinase B antagonists & inhibitors, Imidazoles therapeutic use, Protein Kinase Inhibitors therapeutic use, Pyrazines therapeutic use
Abstract

Imidazo-[1, 2-a]pyrazine 1 is a potent inhibitor of Aurora A and B kinase in vitro and is effective in in vivo tumor models, but has poor oral bioavailbility and is unsuitable for oral dosing. We describe herein our effort to improve oral exposure in this class, resulting ultimately in the identification of a potent Aurora inhibitor 16, which exhibited good drug exposure levels across species upon oral dosing, and showed excellent in vivo efficacy in a mouse xenograft tumor model when dosed orally., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Published
2018
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2. Concise syntheses and HCV NS5B polymerase inhibition of (2'R)-3 and (2'S)-2'-ethynyluridine-10 and related nucleosides.

Author

Bennett F, Buevich AV, Huang HC, Girijavallabhan V, Kerekes AD, Huang Y, Malikzay A, Smith E, Ferrari E, Senior M, Osterman R, Wang L, Wang J, Pu H, Truong QT, Tawa P, Bogen SL, Davies IW, and Weber AE

Subjects
Antiviral Agents chemical synthesis, Antiviral Agents chemistry, Dose-Response Relationship, Drug, Microbial Sensitivity Tests, Molecular Conformation, Nucleosides chemical synthesis, Nucleosides chemistry, Structure-Activity Relationship, Uridine analogs & derivatives, Uridine chemistry, Antiviral Agents pharmacology, Hepacivirus drug effects, Nucleosides pharmacology, Uridine pharmacology, Viral Nonstructural Proteins antagonists & inhibitors
Abstract

(2'R)-Ethynyl uridine 3, and its (2'S)-diastereomer 10, are synthesised in a divergent fashion from the inexpensive parent nucleoside. Both nucleoside analogues are obtained from a total of 5 simple synthetic steps and 3 trivial column chromatography purifications. To evaluate their effectiveness against HCV NS5B polymerase, the nucleosides were converted to their respective 5'-O-triphosphates. Subsequently, this lead to the discovery of the 2'-β-ethynyl 18 and -propynyl 20 nucleotides having significantly improved potency over Sofosbuvir triphosphate 24., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Published
2017
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3. Bioisosteric approach to the discovery of imidazo[1,2-a]pyrazines as potent Aurora kinase inhibitors.

Author

Meng Z, Kulkarni BA, Kerekes AD, Mandal AK, Esposite SJ, Belanger DB, Reddy PA, Basso AD, Tevar S, Gray K, Jones J, Smith EB, Doll RJ, and Siddiqui MA

Subjects
Animals, Aurora Kinase A, Aurora Kinases, Drug Evaluation, Preclinical, Imidazoles chemical synthesis, Imidazoles pharmacokinetics, Protein Kinase Inhibitors chemical synthesis, Protein Kinase Inhibitors pharmacokinetics, Protein Serine-Threonine Kinases metabolism, Pyrazines chemical synthesis, Pyrazines pharmacokinetics, Rats, Imidazoles chemistry, Protein Kinase Inhibitors chemistry, Protein Serine-Threonine Kinases antagonists & inhibitors, Pyrazines chemistry
Abstract

Our continued effort toward the development of the imidazo[1,2-a]pyrazine scaffold as Aurora kinase inhibitors is described. Bioisosteric approach was applied to optimize the 8-position of the core. Several new potent Aurora A/B dual inhibitors, such as 25k and 25l, were identified., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Published
2011
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