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Your search keyword '"Vandna"' showing total 16 results
Start Over Author "Vandna" Journal bioorganic & medicinal chemistry letters
16 results on '"Vandna"'

1. Discovery of thiazolylpyridinone SCD1 inhibitors with preferential liver distribution and reduced mechanism-based adverse effects

Author

Rostam Namdari, Jianmin Fu, Brian K. Hubbard, Kuldip Khakh, Suzie Ferreira, Michael D. Winther, Zaihui Zhang, Vandna Raina, Duanjie Hou, Natalie Dales, David G. McLaren, Leslie G. Ratkay, Pokrovskaia Natalia, Shaoyi Sun, and Monica Mork

Subjects
Pyridones, Clinical Biochemistry, Pharmaceutical Science, Pharmacology, Biochemistry, Mice, In vivo, Drug Discovery, Animals, Humans, Distribution (pharmacology), Peptide bond, Moiety, Potency, Tissue Distribution, Molecular Biology, ED50, Dose-Response Relationship, Drug, Chemistry, Organic Chemistry, Hep G2 Cells, In vitro, Rats, Liver, Rats, Inbred Lew, Microsome, Molecular Medicine, lipids (amino acids, peptides, and proteins), Caco-2 Cells, Stearoyl-CoA Desaturase
Abstract

We discovered a series of novel and potent thiazolylpyridinone-based SCD1 inhibitors based on a 2-aminothiazole HTS hit by replacing the amide bond with a pyridinone moiety. Compound 19 demonstrated good potency against SCD1 in vitro and in vivo. The mouse liver microsomal SCD1 in vitro potency for 19 was improved by more than 240-fold compared to the original HTS hit. Furthermore, 19 demonstrated a dose-dependent reduction of plasma desaturation index with an ED50 of 6.3 mg/kg. Compound 19 demonstrated high liver to plasma and liver to eyelid exposures, indicating preferential liver distribution. The preliminary toxicology study with compound 19 did not demonstrate adverse effects related to SCD1 inhibition, suggesting a wide safety margin with respect to other known SCD1 inhibitors with wider distribution profiles.

Published
2014

2. Design and synthesis of pyridone inhibitors of non-nucleoside reverse transcriptase

Author

Yuexia Liang, Daniel DeStefano, Samson M. Jolly, Georgia B. McGaughey, Joe P. Vacca, Bang-Lin Wan, Michael W. Miller, Robert P. Gomez, Youwei Yan, Sinoeun Touch, Neville J. Anthony, Robert M. Tynebor, Ming-Tain Lai, Rosa I. Sanchez, Vandna Munshi, Thomas J. Tucker, Theresa M. Williams, Peter J. Felock, and Brenda Paton

Subjects
Pyridines, Pyridones, Stereochemistry, Clinical Biochemistry, Mutant, Pharmaceutical Science, Ether, Biochemistry, Cell Line, chemistry.chemical_compound, Protein structure, Drug Discovery, Humans, Computer Simulation, Binding site, Molecular Biology, Indazole, Binding Sites, Organic Chemistry, HIV, virus diseases, HIV Reverse Transcriptase, Reverse transcriptase, Protein Structure, Tertiary, Enzyme Activation, chemistry, Cell culture, Drug Design, Pyrazoles, Reverse Transcriptase Inhibitors, Molecular Medicine, Nucleoside
Abstract

Next generation NNRTIs are sought which possess both broad spectrum antiviral activity against key mutant strains and a high genetic barrier to the selection of new mutant viral strains. Pyridones were evaluated as an acyclic conformational constraint to replace the aryl ether core of MK-4965 (1) and the more rigid indazole constraint of MK-6186 (2). The resulting pyridone compounds are potent inhibitors of HIV RT and have antiviral activity in cell culture that is superior to other next generation NNRTI's.

Published
2011

3. Discovery of XEN907, a spirooxindole blocker of NaV1.7 for the treatment of pain

Author

Shifeng Liu, Jianmin Fu, Rainbow Kwan, Ray Chui, Cadieux Jean-Jacques, Mikhail Chafeev, Vandna Raina, Wendy B. Young, Sultan Chowdhury, and Jianyu Sun

Subjects
Indoles, Stereochemistry, Clinical Biochemistry, Pain, Pharmaceutical Science, Biochemistry, Sodium Channels, Inhibitory Concentration 50, Structure-Activity Relationship, chemistry.chemical_compound, Sodium channel blocker, Drug Discovery, Humans, Potency, Structure–activity relationship, Inhibitory concentration 50, Spiro Compounds, Oxindole, Molecular Biology, Analgesics, Molecular Structure, NAV1.7 Voltage-Gated Sodium Channel, Organic Chemistry, Antagonist, Oxindoles, HEK293 Cells, Gene Expression Regulation, chemistry, Lactam, Molecular Medicine, Lead compound
Abstract

Starting from the oxindole 2a identified through a high-throughput screening campaign, a series of Na(V)1.7 blockers were developed. Following the elimination of undesirable structural features, preliminary optimization of the oxindole C-3 and N-1 substituents afforded the simplified analogue 9b, which demonstrated a 10-fold increase in target potency versus the original HTS hit. A scaffold rigidification strategy then led to the discovery of XEN907, a novel spirooxindole Na(V)1.7 blocker. This lead compound, which in turn showed a further 10-fold increase in potency, represents a promising structure for further optimization efforts.

Published
2011

4. The design and synthesis of diaryl ether second generation HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with enhanced potency versus key clinical mutations

Author

Theresa M. Williams, Youwei Yan, Michael W. Miller, Joseph P. Vacca, Rebecca Perlow-Poehnelt, Bang-Lin Wan, Ming-Tain Lai, Sridhar Prasad, Saggar Sandeep A, Georgia B. McGaughey, Maricel Torrent, Robert M. Tynebor, Rosa I. Sanchez, John T. Sisko, Yuexia Liang, Peter J. Felock, Jessica A. Flynn, Thomas J. Tucker, Meiquing Liu, Gregory Moyer, and Vandna Munshi

Subjects
Molecular model, Anti-HIV Agents, Stereochemistry, Clinical Biochemistry, Pharmaceutical Science, Crystallography, X-Ray, Virus Replication, medicine.disease_cause, Biochemistry, Chemical synthesis, Nucleoside Reverse Transcriptase Inhibitor, Structure-Activity Relationship, Drug Resistance, Viral, Drug Discovery, medicine, Structure–activity relationship, Molecular Biology, chemistry.chemical_classification, Mutation, Binding Sites, Reverse-transcriptase inhibitor, Chemistry, Organic Chemistry, Nucleosides, Nucleotidyltransferase, Enzyme, Models, Chemical, Drug Design, HIV-1, Reverse Transcriptase Inhibitors, Molecular Medicine, Ethers, medicine.drug
Abstract

Using a combination of traditional Medicinal Chemistry/SAR analysis, crystallography, and molecular modeling, we have designed and synthesized a series of novel, highly potent NNRTIs that possess broad antiviral activity against a number of key clinical mutations.

Published
2008

8. Biaryl ethers as potent allosteric inhibitors of reverse transcriptase and its key mutant viruses: Aryl substituted pyrazole as a surrogate for the pyrazolopyridine motif

Author

Su, Dai-Shi, Lim, John J., Tinney, Elizabeth, Tucker, Thomas J., Saggar, Sandeep, Sisko, John T., Wan, Bang-Lin, Young, Mary Beth, Anderson, Kenneth D., Rudd, Deanne, Munshi, Vandna, Bahnck, Carolyn, Felock, Peter J., Lu, Meiquing, Lai, Ming-Tain, Touch, Sinoeun, Moyer, Gregory, DiStefano, Daniel J., Flynn, Jessica A., Liang, Yuexia, Sanchez, Rosa, Perlow-Poehnelt, Rebecca, Miller, Mike, Vacca, Joe P., Williams, Theresa M., and Anthony, Neville J.

Published
2010
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9. Substituted tetrahydroquinolines as potent allosteric inhibitors of reverse transcriptase and its key mutants

Author

Su, Dai-Shi, Lim, John J., Tinney, Elizabeth, Wan, Bang-Lin, Young, Mary Beth, Anderson, Kenneth D., Rudd, Deanne, Munshi, Vandna, Bahnck, Carolyn, Felock, Peter J., Lu, Meiqing, Lai, Ming-Tain, Touch, Sinoeun, Moyer, Gregory, DiStefano, Daniel J., Flynn, Jessica A., Liang, Yuexia, Sanchez, Rosa, Prasad, Sridhar, Yan, Youwei, Perlow-Poehnelt, Rebecca, Torrent, Maricel, Miller, Mike, Vacca, Joe P., Williams, Theresa M., and Anthony, Neville J.

Published
2009
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11. The design and synthesis of diaryl ether second generation HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with enhanced potency versus key clinical mutations

Author

Tucker, Thomas J., Saggar, Sandeep, Sisko, John T., Tynebor, Robert M., Williams, Theresa M., Felock, Peter J., Flynn, Jessica A., Lai, Ming-Tain, Liang, Yuexia, McGaughey, Georgia, Liu, Meiquing, Miller, Mike, Moyer, Gregory, Munshi, Vandna, Perlow-Poehnelt, Rebecca, Prasad, Sridhar, Sanchez, Rosa, Torrent, Maricel, Vacca, Joseph P., Wan, Bang-Lin, and Yan, Youwei

Published
2008
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13. Corrigendum to “Novel indole-3-sulfonamides as potent HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs)” [Bioorg. Med. Chem. Lett. (2008) 554]

Author

Zhao, Zhijian, primary, Wolkenberg, Scott E., additional, Sanderson, Philip E.J., additional, Lu, Meiqing, additional, Munshi, Vandna, additional, Moyer, Gregory, additional, Feng, Meizhen, additional, Carella, Anthony V., additional, Ecto, Linda T., additional, Gabryelski, Lori J., additional, Lai, Ming-Tain, additional, Prasad, Sridar G., additional, Yan, Youwei, additional, McGaughey, Georgia B., additional, Miller, Michael D., additional, Lindsley, Craig W., additional, Hartman, George D., additional, Vacca, Joseph P., additional, and Williams, Theresa M., additional

Published
2010
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14. Corrigendum to 'Novel indole-3-sulfonamides as potent HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs)' [Bioorg. Med. Chem. Lett. (2008) 554]

Author

Linda T. Ecto, Georgia B. McGaughey, Sridar G. Prasad, George D. Hartman, Lori Gabryelski, Sanderson Philip E, Theresa M. Williams, Zhijian Zhao, Anthony Carella, Youwei Yan, Ming-Tain Lai, Meiqing Lu, Meizhen Feng, Craig W. Lindsley, Gregory Moyer, Joseph P. Vacca, Scott E. Wolkenberg, Michael D. Miller, and Vandna Munshi

Subjects
Indole test, Chemistry, Organic Chemistry, Clinical Biochemistry, Human immunodeficiency virus (HIV), Pharmaceutical Science, medicine.disease_cause, Biochemistry, Virology, Nucleoside Reverse Transcriptase Inhibitor, Drug Discovery, medicine, Molecular Medicine, Molecular Biology
Published
2010

15. Tetrazole thioacetanilides: Potent non-nucleoside inhibitors of WT HIV reverse transcriptase and its K103N mutant

Author

Muraglia, Ester, primary, Kinzel, Olaf D., additional, Laufer, Ralph, additional, Miller, Michael D., additional, Moyer, Gregory, additional, Munshi, Vandna, additional, Orvieto, Federica, additional, Palumbi, Maria Cecilia, additional, Pescatore, Giovanna, additional, Rowley, Michael, additional, Williams, Peter D., additional, and Summa, Vincenzo, additional

Published
2006
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16. Discovery of XEN907, a spirooxindole blocker of NaV1.7 for the treatment of pain

Author

Chowdhury, Sultan, Chafeev, Mikhail, Liu, Shifeng, Sun, Jianyu, Raina, Vandna, Chui, Ray, Young, Wendy, Kwan, Rainbow, Fu, Jianmin, and Cadieux, Jay A.

Subjects
*PHARMACEUTICAL research, *INDOLE, *PAIN management, *HIGH throughput screening (Drug development), *DRUG synergism, *TARGETED drug delivery, *MOLECULAR structure, *LEAD compounds, *SODIUM channels
Abstract

Abstract: Starting from the oxindole 2a identified through a high-throughput screening campaign, a series of NaV1.7 blockers were developed. Following the elimination of undesirable structural features, preliminary optimization of the oxindole C-3 and N-1 substituents afforded the simplified analogue 9b, which demonstrated a 10-fold increase in target potency versus the original HTS hit. A scaffold rigidification strategy then led to the discovery of XEN907, a novel spirooxindole NaV1.7 blocker. This lead compound, which in turn showed a further 10-fold increase in potency, represents a promising structure for further optimization efforts. [Copyright &y& Elsevier]

Published
2011
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