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20 results on '"Wieting, Joshua M."'

2. The discovery of VU0652957 (VU2957, Valiglurax): SAR and DMPK challenges en route to an mGlu4 PAM development candidate

Author

Panarese, Joseph D., primary, Engers, Darren W., additional, Wu, Yong-Jin, additional, Guernon, Jason M., additional, Chun, Aspen, additional, Gregro, Alison R., additional, Bender, Aaron M., additional, Capstick, Rory A., additional, Wieting, Joshua M., additional, Bronson, Joanne J., additional, Macor, John E., additional, Westphal, Ryan, additional, Soars, Matthew, additional, Engers, Julie E., additional, Felts, Andrew S., additional, Rodriguez, Alice L., additional, Emmitte, Kyle A., additional, Jones, Carrie K., additional, Blobaum, Anna L., additional, Jeffrey Conn, P., additional, Niswender, Colleen M., additional, Hopkins, Corey R., additional, and Lindsley, Craig W., additional

Published
2019
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3. Discovery of Novel Central Nervous System Penetrant Metabotropic Glutamate Receptor Subtype 2 (mGlu2) Negative Allosteric Modulators (NAMs) Based on Functionalized Pyrazolo[1,5-a]pyrimidine-5-carboxamide and Thieno[3,2-b]pyridine-5-carboxamide Cores

Author

Childress, Elizabeth S., primary, Wieting, Joshua M., additional, Felts, Andrew S., additional, Breiner, Megan M., additional, Long, Madeline F., additional, Luscombe, Vincent B., additional, Rodriguez, Alice L., additional, Cho, Hyekyung P., additional, Blobaum, Anna L., additional, Niswender, Colleen M., additional, Emmitte, Kyle A., additional, Conn, P. Jeffrey, additional, and Lindsley, Craig W., additional

Published
2018
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9. Discovery of Novel Central Nervous System Penetrant Metabotropic Glutamate Receptor Subtype 2 (mGlu2) Negative Allosteric Modulators (NAMs) Based on Functionalized Pyrazolo[1,5-a]pyrimidine-5-carboxamide and Thieno[3,2-b]pyridine-5-carboxamide Cores

Author

Childress, Elizabeth S., Wieting, Joshua M., Felts, Andrew S., Breiner, Megan M., Long, Madeline F., Luscombe, Vincent B., Rodriguez, Alice L., Cho, Hyekyung P., Blobaum, Anna L., Niswender, Colleen M., Emmitte, Kyle A., Conn, P. Jeffrey, and Lindsley, Craig W.

Abstract

A scaffold hopping exercise from a monocyclic mGlu2NAM with poor rodent PK led to two novel heterobicyclic series of mGlu2NAMs based on either a functionalized pyrazolo[1,5-a]pyrimidine-5-carboxamide core or a thieno[3,2-b]pyridine-5-carboxamide core. These novel analogues possess enhanced rodent PK, while also maintaining good mGlu2NAM potency, selectivity (versus mGlu3and the remaining six mGlu receptors), and high CNS penetration. Interestingly, SAR was divergent between the new 5,6-heterobicyclic systems.

Published
2019
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14. Evidence of Enhanced Conjugation in ortho-Arylene Ethynylenes with Transition Metal Coordination

Author

Ren, Qianwei, primary, Reedy, Cole G., additional, Terrell, Eric A., additional, Wieting, Joshua M., additional, Wagie, Robert W., additional, Asplin, Jake P., additional, Doyle, Leah M., additional, Long, Steven J., additional, Everard, Michael T., additional, Sauer, Jon S., additional, Baumgart, Cassandra E., additional, D’Acchioli, Jason S., additional, and Bowling, Nathan P., additional

Published
2012
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17. Preparation and Catalytic Activity of BINOL-Derived Silanediols.

Author

Wieting, Joshua M., Fisher, Thomas J., Schafer, Andrew G., Visco, Michael D., Gallucci, Judith C., and Mattson, Anita E.

Subjects
*BINAPHTHOL, *HYDROGEN bonding, *STEREOSELECTIVE reactions, *KETENES, *CRYSTAL structure
Abstract

Enantiopure silanediols derived from BINOL are an innovative family of stereoselective hydrogen-bond donor (HBD) catalysts. Silanediols incorporated into a BINOL framework are attractive catalysts, as they are readily accessible and highly customizable. Structural modifications of the BINOL backbone affect the reactivity and selectivity of the silanediol catalysts in the additions of silyl ketene acetals to N-acyl isoquinolinium ions. The best results were obtained when the silanediol scaffold was substituted at the 4,4′- and 6,6′-positions. This report includes details regarding the properties of selected BINOL-based silanediol catalysts, including their acidities, binding constants, and X-ray crystal structures. [ABSTRACT FROM AUTHOR]

Published
2015
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19. The discovery of VU0652957 (VU2957, Valiglurax): SAR and DMPK challenges en route to an mGlu 4 PAM development candidate.

Author

Panarese JD, Engers DW, Wu YJ, Guernon JM, Chun A, Gregro AR, Bender AM, Capstick RA, Wieting JM, Bronson JJ, Macor JE, Westphal R, Soars M, Engers JE, Felts AS, Rodriguez AL, Emmitte KA, Jones CK, Blobaum AL, Conn PJ, Niswender CM, Hopkins CR, and Lindsley CW

Subjects
Allosteric Regulation drug effects, Dose-Response Relationship, Drug, Heterocyclic Compounds, 2-Ring chemistry, Humans, Isoquinolines chemistry, Molecular Structure, Myotonin-Protein Kinase metabolism, Structure-Activity Relationship, Drug Discovery, Heterocyclic Compounds, 2-Ring pharmacology, Isoquinolines pharmacology, Myotonin-Protein Kinase antagonists & inhibitors, Receptors, Metabotropic Glutamate metabolism
Abstract

This letter describes the first account of the chemical optimization (SAR and DMPK profiling) of a new series of mGlu 4 positive allosteric modulators (PAMs), leading to the identification of VU0652957 (VU2957, Valiglurax), a compound profiled as a preclinical development candidate. Here, we detail the challenges faced in allosteric modulator programs (e.g., steep SAR, as well as subtle structural changes affecting overall physiochemical/DMPK properties and CNS penetration)., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Published
2019
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20. Discovery of Novel Central Nervous System Penetrant Metabotropic Glutamate Receptor Subtype 2 (mGlu 2 ) Negative Allosteric Modulators (NAMs) Based on Functionalized Pyrazolo[1,5- a]pyrimidine-5-carboxamide and Thieno[3,2- b]pyridine-5-carboxamide Cores.

Author

Childress ES, Wieting JM, Felts AS, Breiner MM, Long MF, Luscombe VB, Rodriguez AL, Cho HP, Blobaum AL, Niswender CM, Emmitte KA, Conn PJ, and Lindsley CW

Subjects
Allosteric Regulation, Amides metabolism, Amides pharmacokinetics, Animals, Drug Evaluation, Preclinical, Half-Life, Humans, Inhibitory Concentration 50, Protein Isoforms chemistry, Protein Isoforms metabolism, Pyrazoles chemistry, Pyridines chemistry, Pyrimidines chemistry, Rats, Receptors, Metabotropic Glutamate metabolism, Structure-Activity Relationship, Amides chemistry, Central Nervous System metabolism, Receptors, Metabotropic Glutamate chemistry
Abstract

A scaffold hopping exercise from a monocyclic mGlu 2 NAM with poor rodent PK led to two novel heterobicyclic series of mGlu 2 NAMs based on either a functionalized pyrazolo[1,5- a]pyrimidine-5-carboxamide core or a thieno[3,2- b]pyridine-5-carboxamide core. These novel analogues possess enhanced rodent PK, while also maintaining good mGlu 2 NAM potency, selectivity (versus mGlu 3 and the remaining six mGlu receptors), and high CNS penetration. Interestingly, SAR was divergent between the new 5,6-heterobicyclic systems.

Published
2019
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