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Your search keyword '"Jay P. Powers"' showing total 6 results
Start Over Author "Jay P. Powers" Journal bioorganic & medicinal chemistry letters
6 results on '"Jay P. Powers"'

1. Discovery and optimization of benzenesulfonanilide derivatives as a novel class of 11β-HSD1 inhibitors

Author

Stefania Ursu, Daqing Sun, Yosup Rew, Juan C. Jaen, Jay P. Powers, Xiao He, Hua Tu, Dustin McMinn, and Michael DeGraffenreid

Subjects
Stereochemistry, Clinical Biochemistry, Drug Evaluation, Preclinical, Molecular Conformation, Pharmaceutical Science, Crystallography, X-Ray, Transfection, Biochemistry, Piperazines, 11β hsd1 inhibitors, Structure-Activity Relationship, 11-beta-Hydroxysteroid Dehydrogenase Type 1, Drug Discovery, Humans, Anilides, Enzyme Inhibitors, Piperazine, Molecular Biology, Biological evaluation, chemistry.chemical_classification, Sulfonamides, Aniline Compounds, Chemistry, Organic Chemistry, Combinatorial chemistry, Sulfonamide, Enzyme Activation, HEK293 Cells, Molecular Medicine, hormones, hormone substitutes, and hormone antagonists
Abstract

A novel series of benzenesulfonanilide derivatives of 11β-HSD1 inhibitors were identified via modification of the sulfonamide core of the arylsulfonylpiperazine lead structures. The synthesis, in vitro biological evaluation, and structure–activity relationship of these compounds are presented. Optimization of this series rapidly resulted in the discovery of compounds (S)-10 and (S)-23 (11β-HSD1 SPA IC50 = 1.8 and 1.4 nM, respectively).

Published
2012

2. Discovery of amide replacements that improve activity and metabolic stability of a bis-amide smoothened antagonist hit

Author

Minqing Rong, Brian Lucas, Wendy Zhong, Guifen Xu, Gary Lee, Ben Jiang, Angela Chong, Qiuping Ye, Michael DeGraffenreid, Tom Huang, Dineli Wickramasinghe, Randall W. Hungate, Wade Aaron, Michael G. Johnson, Jessica Orf, Dustin McMinn, Matthew L. Brown, Richard J. Austin, Maria M. Toteva, Jacob Kaizerman, and Jay P. Powers

Subjects
Molecular Structure, Drug discovery, Chemistry, Organic Chemistry, Clinical Biochemistry, Antagonist, Pharmaceutical Science, Stereoisomerism, Amides, Biochemistry, Hedgehog signaling pathway, In vitro, High-Throughput Screening Assays, Structure-Activity Relationship, chemistry.chemical_compound, In vivo, Amide, Drug Discovery, Molecular Medicine, Structure–activity relationship, Enzyme Inhibitors, Smoothened, Molecular Biology, Acyltransferases
Abstract

A bis-amide antagonist of Smoothened, a seven-transmembrane receptor in the Hedgehog signaling pathway, was discovered via high throughput screening. In vitro and in vivo experiments demonstrated that the bis-amide was susceptible to N-acyl transferase mediated amide scission. Several bioisosteric replacements of the labile amide that maintained in vitro potency were identified and shown to be metabolically stable in vitro and in vivo.

Published
2011

3. Synthesis and optimization of novel 4,4-disubstituted cyclohexylbenzamide derivatives as potent 11β-HSD1 inhibitors

Author

Hua Tu, Lisa Julian, Nigel Walker, Maren Gulsrud Willcockson, Yosup Rew, Michael DeGraffenreid, Zhulun Wang, Juan C. Jaen, Daqing Sun, Ron C. Kelly, Athena Sudom, Seb Caille, Jacob Kaizerman, Jay P. Powers, Xuelei Yan, Qiuping Ye, Stefania Ursu, Ben Jiang, Felix Gonzalez-Lopez de Turiso, Randall W. Hungate, and Dustin McMinn

Subjects
medicine.drug_class, Clinical Biochemistry, Administration, Oral, Pharmaceutical Science, Carboxamide, Crystallography, X-Ray, Biochemistry, Chemical synthesis, 11β hsd1 inhibitors, Structure-Activity Relationship, 11-beta-Hydroxysteroid Dehydrogenase Type 1, Drug Discovery, medicine, Animals, Humans, Structure–activity relationship, Enzyme Inhibitors, Molecular Biology, chemistry.chemical_classification, Binding Sites, biology, Chemistry, Organic Chemistry, Highly selective, Combinatorial chemistry, Rats, Macaca fascicularis, Enzyme, Enzyme inhibitor, Benzamides, Microsomes, Liver, biology.protein, Molecular Medicine, Ex vivo
Abstract

The synthesis and SAR of a series of 4,4-disubstituted cyclohexylbenzamide inhibitors of 11β-HSD1 are described. Optimization rapidly led to potent, highly selective, and orally bioavailable inhibitors demonstrating efficacy in both rat and non-human primate ex vivo pharmacodynamic models.

Published
2011

4. Discovery and Initial SAR of Arylsulfonylpiperazine Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1)

Author

Qiuping Ye, Daqing Sun, Jay P. Powers, Liang Tang, Craig Tomooka, Stefania Ursu, Hua Tu, Yongmei Di, Athena Sudom, Xuelei Yan, Juan C. Jaen, Shichang Miao, Nigel Walker, Ji Ma, Zhulun Wang, and Marc Labelle

Subjects
Models, Molecular, Stereochemistry, Clinical Biochemistry, Nitro compound, Pharmaceutical Science, Dehydrogenase, Crystallography, X-Ray, Biochemistry, Isozyme, Chemical synthesis, Piperazines, Small Molecule Libraries, Mice, Structure-Activity Relationship, Oxidoreductase, 11-beta-Hydroxysteroid Dehydrogenase Type 1, Drug Discovery, Animals, Humans, Sulfhydryl Compounds, Enzyme Inhibitors, Hydroxysteroid dehydrogenase, Molecular Biology, chemistry.chemical_classification, Binding Sites, Molecular Structure, biology, Chemistry, Organic Chemistry, Stereoisomerism, Molecular Weight, Enzyme, Enzyme inhibitor, Drug Design, biology.protein, Molecular Medicine, hormones, hormone substitutes, and hormone antagonists
Abstract

High-throughput screening of a small-molecule compound library resulted in the identification of a series of arylsulfonylpiperazines that are potent and selective inhibitors of human 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1). Optimization of the initial lead resulted in the discovery of compound (R)-45 (11β-HSD1 IC50 = 3 nM).

Published
2008

5. SAR studies on a novel series of human cytomegalovirus primase inhibitors

Author

H. DiMaio, Xi Chen, Jay P. Powers, Lingming Liang, Matt Wright, C. Stein, M.G. Peterson, J. Adrian, V. Mayorga, F. Spector, D. Xu, Timothy D. Cushing, Juan C. Jaen, Shichang Miao, and Qiuping Ye

Subjects
DNA Replication, Ganciclovir, Human cytomegalovirus, Drug-Related Side Effects and Adverse Reactions, viruses, Clinical Biochemistry, Administration, Oral, Biological Availability, Cytomegalovirus, Pharmaceutical Science, DNA Primase, Antiviral Agents, Biochemistry, Virus, Inhibitory Concentration 50, Structure-Activity Relationship, chemistry.chemical_compound, Drug Discovery, medicine, Animals, Humans, Cytotoxicity, Molecular Biology, Organic Chemistry, virus diseases, Viral Load, medicine.disease, Virology, In vitro, Rats, Pyrimidines, chemistry, Molecular Medicine, Primase, DNA, medicine.drug, Cidofovir
Abstract

A novel series of imidazolylpyrimidines were found to possess inhibitory activity against the human CMV UL70 primase. Extensive SAR studies on an HTS lead led to potent, orally bioavailable compounds with anti-CMV IC 50 values of 150 nM in both viral yield and viral DNA replication assays and with a much reduced cytotoxicity compared to marketed treatments ganciclovir and cidofovir.

Published
2007

6. Discovery and initial SAR of inhibitors of interleukin-1 receptor-associated kinase-4

Author

Juan C. Jaen, Jay P. Powers, Nigel Walker, Zhulun Wang, Holger Wesche, Jinqian Liu, and Shyun Li

Subjects
Alkylation, High-throughput screening, Clinical Biochemistry, Pharmaceutical Science, Protein Serine-Threonine Kinases, Interleukin-1 receptor, Biochemistry, Structure-Activity Relationship, Drug Discovery, Structure–activity relationship, Protein kinase A, Protein Kinase Inhibitors, Molecular Biology, Molecular Structure, biology, Kinase, Chemistry, Organic Chemistry, Intracellular Signaling Peptides and Proteins, Amides, Small molecule, Cross-Linking Reagents, Interleukin-1 Receptor-Associated Kinases, Enzyme inhibitor, biology.protein, Cancer research, Molecular Medicine, Benzimidazoles, Signal transduction
Abstract

High-throughput screening of a small-molecule compound library resulted in the identification of a novel series of N-acyl 2-aminobenzimidazoles that are potent inhibitors of interleukin-1 receptor-associated kinase-4.

Published
2006

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