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Your search keyword '"Robert H. Stoffel"' showing total 4 results
Start Over Author "Robert H. Stoffel" Journal bioorganicmedicinal chemistry letters
4 results on '"Robert H. Stoffel"'

1. Discovery and optimization of (R)-prolinol-derived agonists of the Growth Hormone Secretagogue receptor (GHSR)

Author

David A. Gordon, Neil Flynn, Dorothy Slusarchyk, Anna Pendri, Samuel Gerritz, Daniel Longhi, Weixu Zhai, Shuhao Shi, Joseph A. Tino, Michael J. Sofia, Robert H. Stoffel, Baoqing Ma, and Brian J. Murphy

Subjects
Agonist, Pyrrolidines, medicine.drug_class, Stereochemistry, Clinical Biochemistry, Growth hormone secretagogue receptor, Pharmaceutical Science, Carboxamide, Biochemistry, Receptors, G-Protein-Coupled, chemistry.chemical_compound, Structure-Activity Relationship, Solid-phase synthesis, Drug Discovery, medicine, Combinatorial Chemistry Techniques, Receptors, Ghrelin, Molecular Biology, G protein-coupled receptor, Molecular Structure, Organic Chemistry, Stereoisomerism, Hit to lead, Protein superfamily, Prolinol, chemistry, Molecular Medicine
Abstract

The discovery and optimization of a novel series of prolinol-derived GHSR agonists is described. This series emerged from a 11,520-member solid-phase library targeting the GPCR protein superfamily, and the rapid optimization of low micromolar hits into single-digit nanomolar leads can be attributed to the solid-phase synthesis of matrix libraries, which revealed multiple non-additive structure-activity relationships. In addition, the separation of potent diastereomers highlighted the influence of the alpha-methyl stereochemistry of the phenoxyacetamide sidechain on GHSR activity.

Published
2008

2. Discovery of small molecule benzimidazole antagonists of the chemokine receptor CXCR3

Author

Dawn M. George, Grier A. Wallace, Wenyan Miao, Agnieszka Bischoff, Martin E. Hayes, David W. Green, Robert H. Stoffel, Mcpherson Michael J, Gregory Roth, and Pintipa Grongsaard

Subjects
Chemokine, Benzimidazole, Receptors, CXCR3, biology, Molecular Structure, Chemistry, Stereochemistry, Organic Chemistry, Clinical Biochemistry, Pharmaceutical Science, CXCR3, Biochemistry, Small molecule, chemistry.chemical_compound, Structure-Activity Relationship, Drug Discovery, biology.protein, Molecular Medicine, Structure–activity relationship, Moiety, CXCL10, Benzimidazoles, Receptor, Molecular Biology
Abstract

High-throughput screening identified a low molecular weight antagonist of CXCR3 displaying micromolar activity in a membrane filtration-binding assay. Systematic modification of the benzimidazole core and tethered acetophenone moiety established tractable SAR of analogs with improved physicochemical properties and sub-micromolar activity across both human and murine receptors.

Published
2007

3. Potent and selective biphenyl azole inhibitors of adipocyte fatty acid binding protein (aFABP)

Author

Thomas B. Lavoie, Steven Sheriff, Leonard P. Adam, Yanting Huang, Donna Bassolino-Klimas, Manorama Patel, Robert H. Stoffel, Yeheng Zhu, Prakash Taunk, Kevin Kish, Terry R. Stouch, David S. Taylor, Rex A. Parker, Jeffrey A. Robl, David R. Magnin, William R. Ewing, Thomas Harrity, Ligaya M. Simpkins, Richard B. Sulsky, and Jacobson Bruce L

Subjects
Azoles, Stereochemistry, Clinical Biochemistry, Pharmaceutical Science, Fatty Acid-Binding Proteins, Biochemistry, Fatty acid-binding protein, chemistry.chemical_compound, Mice, Radioligand Assay, Adipocyte, Drug Discovery, Adipocytes, Animals, Hypoglycemic Agents, adipocyte protein 2, Binding site, Molecular Biology, Hypolipidemic Agents, Binding Sites, biology, Chemistry, Binding protein, Organic Chemistry, Biphenyl Compounds, Ligand (biochemistry), Disease Models, Animal, Models, Chemical, biology.protein, Molecular Medicine, Fatty Acid Binding Protein 3, Epidermis
Abstract

Herein we report the first disclosure of biphenyl azoles that are nanomolar binders of adipocyte fatty acid binding protein (aFABP or aP2) with up to thousand-fold selectivity against muscle fatty acid binding protein and epidermal fatty acid binding protein. In addition a new radio-ligand to determine binding against the three fatty acid binding proteins was also synthesized.

Published
2006

4. Tetrahydroisoquinoline 1-carboxamides as growth hormone secretagogues

Author

Brian J. Murphy, Melissa Kung, Fucheng Qu, James J. Li, Gary J. Grover, Kenneth E.J. Dickinson, Neil Flynn, Dorothy Slusarchyk, Haixia Wang, David A. Gordon, Joseph A. Tino, Paul G. Sleph, Robert H. Stoffel, Ramakrishna Seethala, Leah Giupponi, Jeffrey A. Robl, Christa M. Musial, and Rajasree Golla

Subjects
medicine.medical_specialty, Tertiary amine, Clinical Biochemistry, Pharmaceutical Science, Biochemistry, Chemical synthesis, Receptors, G-Protein-Coupled, chemistry.chemical_compound, In vivo, Internal medicine, Tetrahydroisoquinolines, Drug Discovery, medicine, Animals, Receptor, Receptors, Ghrelin, Molecular Biology, Oligopeptide, Tetrahydroisoquinoline, Organic Chemistry, In vitro, Rats, Endocrinology, chemistry, Models, Chemical, Growth Hormone, Molecular Medicine, Ghrelin, Hydrophobic and Hydrophilic Interactions, Oligopeptides
Abstract

Several novel series of tetrahydroisoquinoline 1-carboxamides were prepared and shown to be potent growth hormone (GH) secretagogues. Among them, carbamate 12a-E2 displays excellent in vivo activity by increasing plasma GH 10-fold in an anesthetized IV rat model.

Published
2005

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