Find Research Outputs

Search concepts
Selected Filters
2019

Discovery of 4-alkoxy-6-methylpicolinamide negative allosteric modulators of metabotropic glutamate receptor subtype 5

Felts, A. S., Bollinger, K. A., Brassard, C. J., Rodriguez, A. L., Morrison, R. D., Scott Daniels, J., Blobaum, A. L., Niswender, C. M., Jones, C. K., Jeffrey Conn, P., Emmitte, K. A. & Lindsley, C. W., 1 Jan 2019, In : Bioorganic and Medicinal Chemistry Letters. 29, 1, p. 47-50 4 p.

Research output: Contribution to journalArticleResearchpeer-review

Aldehyde Oxidase
Metabotropic Glutamate 5 Receptor
Metabotropic Glutamate Receptors
Metabolism
Modulators

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

Childress, E. S., Wieting, J. M., Felts, A. S., Breiner, M. M., Long, M. F., Luscombe, V. B., Rodriguez, A. L., Cho, H. P., Blobaum, A. L., Niswender, C. M., Emmitte, K. A., Conn, P. J. & Lindsley, C. W., 1 Oct 2019, In : Journal of Medicinal Chemistry. 62, 1, p. 378-384 7 p.

Research output: Contribution to journalArticleResearchpeer-review

Rodentia
Central Nervous System
pyridine
pyrazolo(1,5-a)pyrimidine
metabotropic glutamate receptor 2

Discovery of Tricyclic Triazolo- and Imidazopyridine Lactams as M 1 Positive Allosteric Modulators

Engers, J. L., Bender, A. M., Kalbfleisch, J. J., Cho, H. P., Lingenfelter, K. S., Luscombe, V. B., Han, C., Melancon, B. J., Blobaum, A. L., Dickerson, J. W., Rook, J. M., Niswender, C. M., Emmitte, K. A., Conn, P. J. & Lindsley, C. W., 20 Mar 2019, In : ACS Chemical Neuroscience. 10, 3, p. 1035-1042 8 p.

Research output: Contribution to journalArticleResearchpeer-review

Lactams
Modulators
Cell Line
Muscarinic Receptors
Cells
3 Citations (Scopus)

Discovery of VU2957 (Valiglurax): An mGlu 4 Positive Allosteric Modulator Evaluated as a Preclinical Candidate for the Treatment of Parkinson's Disease

Panarese, J. D., Engers, D. W., Wu, Y. J., Bronson, J. J., Macor, J. E., Chun, A., Rodriguez, A. L., Felts, A. S., Engers, J. L., Loch, M. T., Emmitte, K. A., Castelhano, A. L., Kates, M. J., Nader, M. A., Jones, C. K., Blobaum, A. L., Conn, P. J., Niswender, C. M., Hopkins, C. R. & Lindsley, C. W., 14 Mar 2019, In : ACS Medicinal Chemistry Letters. 10, 3, p. 255-260 6 p.

Research output: Contribution to journalArticleResearchpeer-review

Pulse amplitude modulation
Toxicology
Modulators
Parkinson Disease
Pharmacology
1 Citation (Scopus)

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

Panarese, J. D., Engers, D. W., Wu, Y. J., Guernon, J. M., Chun, A., Gregro, A. R., Bender, A. M., Capstick, R. A., Wieting, J. M., Bronson, J. J., Macor, J. E., Westphal, R., Soars, M., Engers, J. E., Felts, A. S., Rodriguez, A. L., Emmitte, K. A., Jones, C. K., Blobaum, A. L., Jeffrey Conn, P. & 3 others, Niswender, C. M., Hopkins, C. R. & Lindsley, C. W., 15 Jan 2019, In : Bioorganic and Medicinal Chemistry Letters. 29, 2, p. 342-346 5 p.

Research output: Contribution to journalArticleResearchpeer-review

Modulators
2018

Discovery of 6-(pyrimidin-5-ylmethyl)quinoline-8-carboxamide negative allosteric modulators of metabotropic glutamate receptor subtype 5

Felts, A. S., Rodriguez, A. L., Morrison, R. D., Blobaum, A. L., Byers, F. W., Daniels, J. S., Niswender, C. M., Conn, P. J., Lindsley, C. W. & Emmitte, K. A., 1 Jun 2018, In : Bioorganic and Medicinal Chemistry Letters. 28, 10, p. 1679-1685 7 p.

Research output: Contribution to journalArticleResearchpeer-review

Metabotropic Glutamate 5 Receptor
Metabotropic Glutamate Receptors
Modulators
Assays
Metabolism

Stress and interferon signalling-mediated apoptosis contributes to pleiotropic anticancer responses induced by targeting NGLY1

Zolekar, A., Lin, V. J. T., Mishra, N. M., Ho, Y. Y., Hayatshahi, H. S., Parab, A., Sampat, R., Liao, X., Hoffmann, P., Liu, J., Emmitte, K. A. & Wang, Y-C., 11 Dec 2018, In : British Journal of Cancer. 119, 12, p. 1538-1551 14 p.

Research output: Contribution to journalArticleResearchpeer-review

Interferons
Melanoma
Apoptosis
Neoplasms
Systems Biology
2017
4 Citations (Scopus)

Co-activation of metabotropic glutamate receptor 3 and beta-adrenergic receptors modulates cyclic-AMP and long-term potentiation, and disrupts memory reconsolidation

Walker, A. G., Sheffler, D. J., Lewis, A. S., Dickerson, J. W., Foster, D. J., Senter, R. K., Moehle, M. S., Lv, X., Stansley, B. J., Xiang, Z., Rook, J. M., Emmitte, K. A., Lindsley, C. W. & Conn, P. J., 1 Dec 2017, In : Neuropsychopharmacology. 42, 13, p. 2553-2566 14 p.

Research output: Contribution to journalArticleResearchpeer-review

Long-Term Potentiation
Receptors, Adrenergic, beta
Cyclic AMP
Glutamic Acid
Adrenergic Receptors
7 Citations (Scopus)

Design and Synthesis of mGlu2 NAMs with Improved Potency and CNS Penetration Based on a Truncated Picolinamide Core

Bollinger, K. A., Felts, A. S., Brassard, C. J., Engers, J. L., Rodriguez, A. L., Weiner, R. L., Cho, H. P., Chang, S., Bubser, M., Jones, C. K., Blobaum, A. L., Niswender, C. M., Conn, P. J., Emmitte, K. A. & Lindsley, C. W., 1 Jan 2017, In : ACS Medicinal Chemistry Letters. 8, 9, p. 919-924 6 p.

Research output: Contribution to journalArticleResearchpeer-review

Neurology
Modulators
Inhibitory Concentration 50
Central Nervous System
Scaffolds
7 Citations (Scopus)

Design and Synthesis of N-Aryl Phenoxyethoxy Pyridinones as Highly Selective and CNS Penetrant mGlu3 NAMs

Engers, J. L., Bollinger, K. A., Weiner, R. L., Rodriguez, A. L., Long, M. F., Breiner, M. M., Chang, S., Bollinger, S. R., Bubser, M., Jones, C. K., Morrison, R. D., Bridges, T. M., Blobaum, A. L., Niswender, C. M., Conn, P. J., Emmitte, K. A. & Lindsley, C. W., 1 Jan 2017, In : ACS Medicinal Chemistry Letters. 8, 9, p. 925-930 6 p.

Research output: Contribution to journalArticleResearchpeer-review

Pyridones
Neurology
Scaffolds
Inhibitory Concentration 50
Rats
1 Citation (Scopus)

Development and kilogram-scale synthesis of mGlu5 negative allosteric modulator VU0424238 (auglurant)

David, T. K., Prashanth, N. K., Rajendraswami, M., Pallalu, D., Castelhano, A. L., Kates, M. J., Blobaum, A. L., Jones, C. K., Emmitte, K. A., Conn, P. J. & Lindsley, C. W., 6 Sep 2017, In : Tetrahedron Letters. 58, 36, p. 3554-3558 5 p.

Research output: Contribution to journalArticleResearchpeer-review

Pharmaceutical Chemistry
Chromatography
Silicon Dioxide
Toxicology
Modulators
5 Citations (Scopus)

Discovery of imidazo[1,2-a]-, [1,2,4]triazolo[4,3-a]-, and [1,2,4]triazolo[1,5-a]pyridine-8-carboxamide negative allosteric modulators of metabotropic glutamate receptor subtype 5

Felts, A. S., Rodriguez, A. L., Morrison, R. D., Bollinger, K. A., Venable, D. F., Blobaum, A. L., Byers, F. W., Thompson Gray, A., Daniels, J. S., Niswender, C. M., Jones, C. K., Conn, P. J., Lindsley, C. W. & Emmitte, K. A., 1 Nov 2017, In : Bioorganic and Medicinal Chemistry Letters. 27, 21, p. 4858-4866 9 p.

Research output: Contribution to journalArticleResearchpeer-review

Metabotropic Glutamate 5 Receptor
Dopamine Plasma Membrane Transport Proteins
Metabotropic Glutamate Receptors
Modulators
Pharmacokinetics
10 Citations (Scopus)

Discovery of N-(5-Fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide (VU0424238): A Novel Negative Allosteric Modulator of Metabotropic Glutamate Receptor Subtype 5 Selected for Clinical Evaluation

Felts, A. S., Rodriguez, A. L., Blobaum, A. L., Morrison, R. D., Bates, B. S., Thompson Gray, A., Rook, J. M., Tantawy, M. N., Byers, F. W., Chang, S., Venable, D. F., Luscombe, V. B., Tamagnan, G. D., Niswender, C. M., Daniels, J. S., Jones, C. K., Conn, P. J., Lindsley, C. W. & Emmitte, K. A., 22 Jun 2017, In : Journal of Medicinal Chemistry. 60, 12, p. 5072-5085 14 p.

Research output: Contribution to journalArticleResearchpeer-review

Metabotropic Glutamate 5 Receptor
Allosteric Site
Macaca fascicularis
Papio
Neurodegenerative Diseases
11 Citations (Scopus)

mGlu5 negative allosteric modulators: a patent review (2013 - 2016)

Emmitte, K. A., 3 Jun 2017, In : Expert Opinion on Therapeutic Patents. 27, 6, p. 691-706 16 p.

Research output: Contribution to journalReview articleResearchpeer-review

Alkynes
Clinical Trials
Expert Testimony
Research
Neurodegenerative Diseases
2016
15 Citations (Scopus)

Discovery and optimization of a novel series of highly CNS penetrant M4 PAMs based on a 5,6-dimethyl-4-(piperidin-1-yl)thieno[2,3-d]pyrimidine core

Wood, M. R., Noetzel, M. J., Engers, J. L., Bollinger, K. A., Melancon, B. J., Tarr, J. C., Han, C., West, M., Gregro, A. R., Lamsal, A., Chang, S., Ajmera, S., Smith, E., Chase, P., Hodder, P. S., Bubser, M., Jones, C. K., Hopkins, C. R., Emmitte, K. A., Niswender, C. M. & 5 others, Wood, M. W., Duggan, M. E., Conn, P. J., Bridges, T. M. & Lindsley, C. W., 1 Jul 2016, In : Bioorganic and Medicinal Chemistry Letters. 26, 13, p. 3029-3033 5 p.

Research output: Contribution to journalArticleResearchpeer-review

Modulators
Rats
Brain
Muscarinic Receptors
Plasmas
6 Citations (Scopus)

Evaluating the disposition of a mixed aldehyde oxidase/cytochrome P450 substrate in rats with attenuated P450 activity

Crouch, R. D., Morrison, R. D., Byers, F. W., Lindsley, C. W., Emmitte, K. A. & Daniels, J. S., 1 Aug 2016, In : Drug Metabolism and Disposition. 44, 8, p. 1296-1303 8 p.

Research output: Contribution to journalArticleResearchpeer-review

Aldehyde Oxidase
Cytochrome P-450 Enzyme System
Drug Interactions
NADP
Area Under Curve
3 Citations (Scopus)

N-Alkylpyrido[1′,2′:1,5]pyrazolo-[4,3-d]pyrimidin-4-amines: A new series of negative allosteric modulators of mGlu1/5 with CNS exposure in rodents

Felts, A. S., Rodriguez, A. L., Morrison, R. D., Venable, D. F., Blobaum, A. L., Byers, F. W., Daniels, J. S., Niswender, C. M., Jones, C. K., Conn, P. J., Lindsley, C. W. & Emmitte, K. A., 15 Apr 2016, In : Bioorganic and Medicinal Chemistry Letters. 26, 8, p. 1894-1900 7 p.

Research output: Contribution to journalArticleResearchpeer-review

Metabotropic Glutamate Receptors
Pharmaceutical Chemistry
Central Nervous System Diseases
Neurology
Modulators
19 Citations (Scopus)

Partial mGlu 5 Negative Allosteric Modulators Attenuate Cocaine-Mediated Behaviors and Lack Psychotomimetic-Like Effects

Gould, R. W., Amato, R. J., Bubser, M., Joffe, M. E., Nedelcovych, M. T., Thompson, A. D., Nickols, H. H., Yuh, J. P., Zhan, X., Felts, A. S., Rodriguez, A. L., Morrison, R. D., Byers, F. W., Rook, J. M., Daniels, J. S., Niswender, C. M., Conn, P. J., Emmitte, K. A., Lindsley, C. W. & Jones, C. K., 1 Mar 2016, In : Neuropsychopharmacology. 41, 4, p. 1166-1178 13 p.

Research output: Contribution to journalArticleResearchpeer-review

Metabotropic Glutamate 5 Receptor
Cocaine
Cocaine-Related Disorders
Therapeutics
Self Administration
63 Citations (Scopus)

Practical Strategies and Concepts in GPCR Allosteric Modulator Discovery: Recent Advances with Metabotropic Glutamate Receptors

Lindsley, C. W., Emmitte, K. A., Hopkins, C. R., Bridges, T. M., Gregory, K. J., Niswender, C. M. & Conn, P. J., 8 Jun 2016, In : Chemical Reviews. 116, 11, p. 6707-6741 35 p.

Research output: Contribution to journalReview articleResearchpeer-review

Metabotropic Glutamate Receptors
Modulators
Ligands
Metabolism
Conformations
22 Citations (Scopus)

Targeting BRCA1-and BRCA2-deficient cells with RAD52 small molecule inhibitors

Huang, F., Goyal, N., Sullivan, K., Hanamshet, K., Patel, M., Mazina, O. M., Wang, C. X., An, W. F., Spoonamore, J., Metkar, S., Emmitte, K. A., Cocklin, S., Skorski, T. & Mazin, A. V., 19 May 2016, In : Nucleic Acids Research. 44, 9, p. 4189-4199 11 p.

Research output: Contribution to journalArticleResearchpeer-review

Mutation
Homologous Recombination
DNA Repair
Ovarian Neoplasms
Libraries
20 Citations (Scopus)

VU0477573: Partial Negative Allosteric Modulator of the Subtype 5 Metabotropic Glutamate Receptor with In Vivo Efficacy

Nickols, H. H., Yuh, J. P., Gregory, K. J., Morrison, R. D., Bates, B. S., Stauffer, S. R., Emmitte, K. A., Bubser, M., Peng, W., Nedelcovych, M. T., Thompson, A., Lv, X., Xiang, Z., Daniels, J. S., Niswender, C. M., Lindsley, C. W., Jones, C. K. & Conn, P. J., 1 Jan 2016, In : The Journal of pharmacology and experimental therapeutics. 356, 1, p. 123-136 14 p.

Research output: Contribution to journalArticleResearchpeer-review

Metabotropic Glutamate 5 Receptor
Central Nervous System
Allosteric Site
Fragile X Syndrome
Inositol Phosphates
2015
70 Citations (Scopus)

Advancing biological understanding and therapeutics discovery with small-molecule probes

Schreiber, S. L., Kotz, J. D., Li, M., Aubé, J., Austin, C. P., Reed, J. C., Rosen, H., White, E. L., Sklar, L. A., Lindsley, C. W., Alexander, B. R., Bittker, J. A., Clemons, P. A., De Souza, A., Foley, M. A., Palmer, M., Shamji, A. F., Wawer, M. J., McManus, O., Wu, M. & 26 others, Zou, B., Yu, H., Golden, J. E., Schoenen, F. J., Simeonov, A., Jadhav, A., Jackson, M. R., Pinkerton, A. B., Chung, T. D. Y., Griffin, P. R., Cravatt, B. F., Hodder, P. S., Roush, W. R., Roberts, E., Chung, D. H., Jonsson, C. B., Noah, J. W., Severson, W. E., Ananthan, S., Edwards, B., Oprea, T. I., Conn, P. J., Hopkins, C. R., Wood, M. R., Stauffer, S. R. & Emmitte, K. A., 1 Jan 2015, In : Cell. 161, 6, p. 1252-1265 14 p.

Research output: Contribution to journalReview articleResearchpeer-review

Molecules
Biological Phenomena
Therapeutics
Biological systems
Medicine
15 Citations (Scopus)

Design of 4-Oxo-1-aryl-1,4-dihydroquinoline-3-carboxamides as Selective Negative Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 2

Felts, A. S., Rodriguez, A. L., Smith, K. A., Engers, J. L., Morrison, R. D., Byers, F. W., Blobaum, A. L., Locuson, C. W., Chang, S., Venable, D. F., Niswender, C. M., Daniels, J. S., Conn, P. J., Lindsley, C. W. & Emmitte, K. A., 25 Nov 2015, In : Journal of Medicinal Chemistry. 58, 22, p. 9027-9040 14 p.

Research output: Contribution to journalArticleResearchpeer-review

Metabotropic Glutamate Receptors
Literature
Patents
Central Nervous System Diseases
Muscarinic Receptors
25 Citations (Scopus)

Discovery of a Selective and CNS Penetrant Negative Allosteric Modulator of Metabotropic Glutamate Receptor Subtype 3 with Antidepressant and Anxiolytic Activity in Rodents

Engers, J. L., Rodriguez, A. L., Konkol, L. C., Morrison, R. D., Thompson, A. D., Byers, F. W., Blobaum, A. L., Chang, S., Venable, D. F., Loch, M. T., Niswender, C. M., Daniels, J. S., Jones, C. K., Conn, P. J., Lindsley, C. W. & Emmitte, K. A., 24 Sep 2015, In : Journal of Medicinal Chemistry. 58, 18, p. 7485-7500 16 p.

Research output: Contribution to journalArticleResearchpeer-review

Metabotropic Glutamate Receptors
Anti-Anxiety Agents
Antidepressive Agents
Rodentia
Pyrazines
48 Citations (Scopus)

Metabotropic glutamate receptor 3 activation is required for long-term depression in medial prefrontal cortex and fear extinction

Walker, A. G., Wenthur, C. J., Xiang, Z., Rook, J. M., Emmitte, K. A., Niswender, C. M., Lindsley, C. W. & Conn, P. J., 27 Jan 2015, In : Proceedings of the National Academy of Sciences of the United States of America. 112, 4, p. 1196-1201 6 p.

Research output: Contribution to journalArticleResearchpeer-review

Prefrontal Cortex
Fear
Depression
Cognition
Bipolar Disorder
18 Citations (Scopus)

Relationship between in vivo receptor occupancy and efficacy of metabotropic glutamate receptor subtype 5 allosteric modulators with different in vitro binding profiles

Rook, J. M., Tantawy, M. N., Ansari, M. S., Felts, A. S., Stauffer, S. R., Emmitte, K. A., Kessler, R. M., Niswender, C. M., Daniels, J. S., Jones, C. K., Lindsley, C. W. & Conn, P. J., 1 Jan 2015, In : Neuropsychopharmacology. 40, 3, p. 755-765 11 p.

Research output: Contribution to journalArticleResearchpeer-review

Metabotropic Glutamate 5 Receptor
Positron-Emission Tomography
Allosteric Site
Ligands
Brain Diseases