{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:22:09Z","timestamp":1788283329591,"version":"build-2803163510"},"reference-count":50,"publisher":"American Chemical Society (ACS)","issue":"7","license":[{"start":{"date-parts":[[2015,5,5]],"date-time":"2015-05-05T00:00:00Z","timestamp":1430784000000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["MH062646"],"award-info":[{"award-number":["MH062646"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["MH097056"],"award-info":[{"award-number":["MH097056"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS032373"],"award-info":[{"award-number":["NS032373"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,7,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Recent progress in the discovery of mGlu1 allosteric modulators has suggested the modulation of mGlu1 could offer possible treatment for a number of central nervous system disorders; however, the available chemotypes are inadequate to fully investigate the therapeutic potential of mGlu1 modulation. To address this issue, we used a fluorescence-based high-throughput screening assay to screen an allosteric modulator-biased library of compounds to generate structurally diverse mGlu1 negative allosteric modulator hits for chemical optimization. Herein, we describe the discovery and characterization of a novel mGlu1 chemotype. This series of succinimide negative allosteric modulators, exemplified by VU0410425, exhibited potent inhibitory activity at rat mGlu1 but was, surprisingly, inactive at human mGlu1. VU0410425 and a set of chemically diverse mGlu1 negative allosteric modulators previously reported in the literature were utilized to examine this species disconnect between rat and human mGlu1 activity. Mutation of the key transmembrane domain residue 757 and functional screening of VU0410425 and the literature compounds suggests that amino acid 757 plays a role in the activity of these compounds, but the contribution of the residue is scaffold specific, ranging from critical to minor. The operational model of allosterism was used to estimate the binding affinities of each compound to compare to functional data. This novel series of mGlu1 negative allosteric modulators provides valuable insight into the pharmacology underlying the disconnect between rat and human mGlu1 activity, an issue that must be understood to progress the therapeutic potential of allosteric modulators of mGlu1.<\/jats:p>","DOI":"10.1021\/cn5000343","type":"journal-article","created":{"date-parts":[[2014,5,5]],"date-time":"2014-05-05T22:11:20Z","timestamp":1399327880000},"page":"597-610","source":"Crossref","is-referenced-by-count":52,"title":["A Novel Class of Succinimide-Derived Negative Allosteric\nModulators of Metabotropic Glutamate Receptor Subtype 1 Provides Insight\ninto a Disconnect in Activity between the Rat and Human Receptors"],"prefix":"10.1021","volume":"5","author":[{"given":"Hyekyung P.","family":"Cho","sequence":"first","affiliation":[{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren W.","family":"Engers","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daryl F.","family":"Venable","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen M.","family":"Niswender","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig W.","family":"Lindsley","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University , , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Jeffrey","family":"Conn","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle A.","family":"Emmitte","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University , , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice L.","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,5,5]]},"reference":[{"key":"2026090113113049900_cit1","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1146\/annurev.pharmtox.011008.145533","article-title":"Metabotropic glutamate receptors: physiology, pharmacology,\nand disease","volume":"50","author":"Niswender","year":"2010","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"2026090113113049900_cit2","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.ejphar.2011.09.025","article-title":"The role of group I mGlu receptors\nin the expression of ethanol-induced conditioned place preference\nand ethanol withdrawal seizures in rats","volume":"670","author":"Kotlinska","year":"2011","journal-title":"Eur.\nJ. Pharmacol."},{"key":"2026090113113049900_cit3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00213-009-1700-7","article-title":"Effects of mGluR1\nantagonism in the dorsal hippocampus on drug context-induced reinstatement\nof cocaine-seeking behavior in rats","volume":"208","author":"Xie","year":"2010","journal-title":"Psychopharmacology"},{"key":"2026090113113049900_cit4","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.neuropharm.2006.07.023","article-title":"mGlu1 receptor\nblockade attenuates cue- and nicotine-induced\nreinstatement of extinguished nicotine self-administration behavior\nin rats","volume":"52","author":"Dravolina","year":"2007","journal-title":"Neuropharmacology"},{"key":"2026090113113049900_cit5","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1124\/jpet.108.138107","article-title":"Pharmacological effects of the metabotropic\nglutamate receptor 1 antagonist compared with those of the metabotropic\nglutamate receptor 5 antagonist and metabotropic glutamate receptor\n2\/3 agonist in rodents: detailed investigations with a selective allosteric\nmetabotropic glutamate receptor 1 antagonist, FTIDC [4-[1-(2-fluoropyridine-3-yl)-5-methyl-1H-1,2,3-triazol-4-yl]-N-isopropyl-N-methy l-3,6-dihydropyridine-1(2H)-carboxamide]","volume":"326","author":"Satow","year":"2008","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2026090113113049900_cit6","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1007\/s00213-005-0169-2","article-title":"Pharmacological characterization\nof stress-induced hyperthermia in DBA\/2 mice using metabotropic and\nionotropic glutamate receptor ligands","volume":"183","author":"Rorick-Kehn","year":"2005","journal-title":"Psychopharmacology"},{"key":"2026090113113049900_cit7","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1007\/s00213-004-2056-7","article-title":"Effects of mGlu1\nreceptor blockade on anxiety-related behaviour in the rat lick suppression\ntest","volume":"179","author":"Steckler","year":"2005","journal-title":"Psychopharmacology"},{"issue":"Suppl 1","key":"2026090113113049900_cit8","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.neuropharm.2005.05.010","article-title":"Anticonvulsant effects\nof LY456236,\na selective mGlu1 receptor antagonist","volume":"49","author":"Shannon","year":"2005","journal-title":"Neuropharmacology"},{"key":"2026090113113049900_cit9","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.eplepsyres.2003.08.001","article-title":"Comparison\nof the effect of glutamate\nreceptor modulators in the 6 Hz and maximal electroshock seizure models","volume":"56","author":"Barton","year":"2003","journal-title":"Epilepsy Res."},{"key":"2026090113113049900_cit10","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1016\/j.bmcl.2011.12.131","article-title":"Fused tricyclic mGluR1 antagonists for the treatment\nof neuropathic pain","volume":"22","author":"Bennett","year":"2012","journal-title":"Bioorg. 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Pharmacol."},{"key":"2026090113113049900_cit13","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1124\/jpet.109.151118","article-title":"Unique antipsychotic activities of\nthe selective metabotropic glutamate receptor 1 allosteric antagonist\n2-cyclopropyl-5-[1-(2-fluoro-3-pyridinyl)-5-methyl-1H-1,2,3-triazol-4-yl]-2,3-dihydro-1H-isoindol-1-one","volume":"330","author":"Satow","year":"2009","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2026090113113049900_cit14","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ejphar.2010.03.046","article-title":"Pharmacological effects of metabotropic\nglutamate receptor ligands on prepulse inhibition in DBA\/2J mice","volume":"639","author":"Hikichi","year":"2010","journal-title":"Eur. J. Pharmacol."},{"key":"2026090113113049900_cit15","doi-asserted-by":"crossref","first-page":"5464","DOI":"10.1016\/j.bmcl.2009.07.097","article-title":"Discovery and in vitro\nand in vivo profiles of 4-fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide as novel class of an orally active metabotropic\nglutamate receptor 1 (mGluR1) antagonist","volume":"19","author":"Satoh","year":"2009","journal-title":"Bioorg.\nMed. Chem. Lett."},{"key":"2026090113113049900_cit16","doi-asserted-by":"crossref","first-page":"5310","DOI":"10.1016\/j.bmcl.2009.07.145","article-title":"Discovery and biological\nprofile of isoindolinone derivatives as novel metabotropic glutamate\nreceptor 1 antagonists: a potential treatment for psychotic disorders","volume":"19","author":"Ito","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2026090113113049900_cit17","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.neuropharm.2003.11.014","article-title":"Metabotropic\nglutamate 1 receptor distribution and occupancy in the rat brain:\na quantitative autoradiographic study using [3H]R214127","volume":"46","author":"Lavreysen","year":"2004","journal-title":"Neuropharmacology"},{"key":"2026090113113049900_cit18","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1124\/mol.63.5.1082","article-title":"[3H]R214127: a novel high-affinity radioligand for\nthe mGlu1 receptor reveals a common binding site shared by multiple\nallosteric antagonists","volume":"63","author":"Lavreysen","year":"2003","journal-title":"Mol. Pharmacol."},{"key":"2026090113113049900_cit19","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1124\/mol.59.5.965","article-title":"BAY36\u20137620:\na potent non-competitive mGlu1 receptor antagonist with inverse agonist\nactivity","volume":"59","author":"Carroll","year":"2001","journal-title":"Mol. Pharmacol."},{"key":"2026090113113049900_cit20","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/j.neuropharm.2004.08.007","article-title":"JNJ16259685, a highly potent, selective\nand systemically\nactive mGlu1 receptor antagonist","volume":"47","author":"Lavreysen","year":"2004","journal-title":"Neuropharmacology"},{"key":"2026090113113049900_cit21","doi-asserted-by":"crossref","first-page":"4366","DOI":"10.1038\/onc.2012.471","article-title":"Metabotropic\nglutamate receptor 1 (Grm1) is an oncogene in epithelial cells","volume":"32","author":"Martino","year":"2013","journal-title":"Oncogene"},{"key":"2026090113113049900_cit22","doi-asserted-by":"crossref","first-page":"7162","DOI":"10.1038\/onc.2008.329","article-title":"Metabotropic glutamate receptor subtype-1 is essential for in vivo\ngrowth of melanoma","volume":"27","author":"Ohtani","year":"2008","journal-title":"Oncogene"},{"key":"2026090113113049900_cit23","doi-asserted-by":"crossref","first-page":"2298","DOI":"10.1158\/0008-5472.CAN-06-3665","article-title":"Metabotropic glutamate\nreceptor 1\nand glutamate signaling in human melanoma","volume":"67","author":"Namkoong","year":"2007","journal-title":"Cancer\nRes."},{"key":"2026090113113049900_cit24","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/s10549-011-1624-x","article-title":"Metabotropic\nglutamate receptor-1: a potential therapeutic\ntarget for the treatment of breast cancer","volume":"132","author":"Speyer","year":"2012","journal-title":"Breast\nCancer Res. Treat."},{"key":"2026090113113049900_cit25","first-page":"446","article-title":"Recent progress in the discovery and development of\nnegative allosteric modulators of mGluR5","volume":"12","author":"Lindsley","year":"2009","journal-title":"Curr.\nOpin. Drug Discovery Dev."},{"key":"2026090113113049900_cit26","doi-asserted-by":"crossref","first-page":"680","DOI":"10.2174\/1568026611109060680","article-title":"mGluR5 negative allosteric modulators overview: a medicinal chemistry\napproach towards a series of novel therapeutic agents","volume":"11","author":"Rocher","year":"2011","journal-title":"Curr. Top. Med. Chem."},{"key":"2026090113113049900_cit27","doi-asserted-by":"crossref","first-page":"3713","DOI":"10.1016\/j.bmcl.2013.05.020","article-title":"N-Acyl-N\u2032-arylpiperazines as negative allosteric\nmodulators of mGlu1: identification of VU0469650, a potent and selective\ntool compound with CNS exposure in rats","volume":"23","author":"Lovell","year":"2013","journal-title":"Bioorg.\nMed. Chem. Lett."},{"key":"2026090113113049900_cit28","doi-asserted-by":"crossref","first-page":"5091","DOI":"10.1016\/j.bmcl.2013.07.029","article-title":"Octahydropyrrolo[3,4-c]pyrrole\nnegative allosteric modulators of mGlu1","volume":"23","author":"Manka","year":"2013","journal-title":"Bioorg.\nMed. Chem. Lett."},{"key":"2026090113113049900_cit29","doi-asserted-by":"crossref","first-page":"7639","DOI":"10.1021\/jm200956q","article-title":"Discovery, synthesis, and structure-activity relationship\ndevelopment of a series of N-4-(2,5-dioxopyrrolidin-1-yl)phenylpicolinamides\n(VU0400195, ML182): characterization of a novel positive allosteric\nmodulator of the metabotropic glutamate receptor 4 (mGlu(4)) with\noral efficacy in an antiparkinsonian animal model","volume":"54","author":"Jones","year":"2011","journal-title":"J. Med. Chem."},{"key":"2026090113113049900_cit30","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1021\/cn400070k","article-title":"Substituted\n1-Phenyl-3-(pyridin-2-yl)urea negative allosteric modulators of mGlu5:\ndiscovery of a new tool compound VU0463841 with activity in rat models\nof cocaine addiction","volume":"4","author":"Amato","year":"2013","journal-title":"ACS Chem. Neurosci."},{"key":"2026090113113049900_cit31","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1124\/mol.112.080531","article-title":"Investigating metabotropic glutamate receptor 5 allosteric\nmodulator cooperativity, affinity, and agonism: enriching structure-function\nstudies and structure-activity relationships","volume":"82","author":"Gregory","year":"2012","journal-title":"Mol. Pharmacol."},{"key":"2026090113113049900_cit32","doi-asserted-by":"crossref","first-page":"4390","DOI":"10.1016\/j.bmcl.2010.06.064","article-title":"3-Cyano-5-fluoro-N-arylbenzamides\nas negative allosteric modulators of mGlu(5): Identification of easily\nprepared tool compounds with CNS exposure in rats","volume":"20","author":"Felts","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2026090113113049900_cit33","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1124\/mol.105.016139","article-title":"A close structural analog of 2-methyl-6-(phenylethynyl)-pyridine\nacts as a neutral allosteric site ligand on metabotropic glutamate\nreceptor subtype 5 and blocks the effects of multiple allosteric modulators","volume":"68","author":"Rodriguez","year":"2005","journal-title":"Mol. Pharmacol."},{"key":"2026090113113049900_cit34","doi-asserted-by":"crossref","first-page":"4098","DOI":"10.1016\/j.bmcl.2008.05.091","article-title":"Synthesis and SAR\nof a mGluR5 allosteric partial antagonist lead: unexpected modulation\nof pharmacology with slight structural modifications to a 5-(phenylethynyl)pyrimidine\nscaffold","volume":"18","author":"Sharma","year":"2008","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2026090113113049900_cit35","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1124\/mol.110.067207","article-title":"Discovery of novel\nallosteric modulators of metabotropic glutamate receptor subtype 5\nreveals chemical and functional diversity and in vivo activity in\nrat behavioral models of anxiolytic and antipsychotic activity","volume":"78","author":"Rodriguez","year":"2010","journal-title":"Mol. Pharmacol."},{"key":"2026090113113049900_cit36","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1124\/mol.105.021857","article-title":"A novel class of\npositive allosteric modulators of metabotropic glutamate receptor\nsubtype 1 interact with a site distinct from that of negative allosteric\nmodulators","volume":"70","author":"Hemstapat","year":"2006","journal-title":"Mol. Pharmacol."},{"key":"2026090113113049900_cit37","doi-asserted-by":"crossref","first-page":"13402","DOI":"10.1073\/pnas.231358298","article-title":"Positive\nallosteric\nmodulators of metabotropic glutamate 1 receptor: characterization,\nmechanism of action, and binding site","volume":"98","author":"Knoflach","year":"2001","journal-title":"Proc.\nNatl. Acad. Sci. U.S.A."},{"key":"2026090113113049900_cit38","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.1016\/j.bmcl.2010.03.004","article-title":"A-ring modifications\non the triazafluorenone core structure and their mGluR1 antagonist\nproperties","volume":"20","author":"Sasikumar","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2026090113113049900_cit39","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1124\/jpet.106.116574","article-title":"Pharmacological characterization\nof a new, orally active and potent\nallosteric metabotropic glutamate receptor 1 antagonist, 4-[1-(2-fluoropyridin-3-yl)-5-methyl-1H-1,2,3-triazol-4-yl]-N-isopropyl-N-methyl-3,6-dihydropyridine-1(2H)-carboxamide\n(FTIDC)","volume":"321","author":"Suzuki","year":"2007","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2026090113113049900_cit40","doi-asserted-by":"crossref","first-page":"2998","DOI":"10.1016\/j.bmcl.2011.03.046","article-title":"Radiosynthesis\nand preliminary evaluation of 4-[18F]fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide as a new positron emission tomography\nligand for metabotropic glutamate receptor subtype 1","volume":"21","author":"Yamasaki","year":"2011","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2026090113113049900_cit41","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s00213-005-2143-4","article-title":"The antinociceptive\nand anxiolytic-like effects of the metabotropic glutamate receptor\n5 (mGluR5) antagonists, MPEP and MTEP, and the mGluR1 antagonist,\nLY456236, in rodents: a comparison of efficacy and side-effect profiles","volume":"179","author":"Varty","year":"2005","journal-title":"Psychopharmacology"},{"key":"2026090113113049900_cit42","doi-asserted-by":"crossref","first-page":"2134","DOI":"10.1021\/jm049499o","article-title":"Synthesis, structure-activity relationship, and receptor\npharmacology of a new series of quinoline derivatives acting as selective,\nnoncompetitive mGlu1 antagonists","volume":"48","author":"Mabire","year":"2005","journal-title":"J. Med. Chem."},{"key":"2026090113113049900_cit43","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.bmcl.2006.10.015","article-title":"Structure-activity\nrelationships of novel non-competitive mGluR1 antagonists: a potential\ntreatment for chronic pain","volume":"17","author":"Owen","year":"2007","journal-title":"Bioorg. Med. Chem.\nLett."},{"key":"2026090113113049900_cit44","unstructured":"Itahana, H., Kamikubo, T., Nozawa, E., Kaku, H., Okada, M., Toya, T., Nakamura, A., and Nagai, S. (2002) Thienopyrimidine Derivative. Patent WO02062803 (A1), Japan."},{"key":"2026090113113049900_cit45","doi-asserted-by":"crossref","first-page":"8340","DOI":"10.1074\/jbc.M211759200","article-title":"Mutational\nanalysis and molecular modeling of the allosteric binding site of\na novel, selective, noncompetitive antagonist of the metabotropic\nglutamate 1 receptor","volume":"278","author":"Malherbe","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2026090113113049900_cit46","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.tips.2007.06.004","article-title":"Allosteric\nGPCR modulators: taking\nadvantage of permissive receptor pharmacology","volume":"28","author":"Leach","year":"2007","journal-title":"Trends Pharmacol. Sci."},{"key":"2026090113113049900_cit47","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1126\/science.1249489","article-title":"Structure of a Class C GPCR Metabotropic\nGlutamate Receptor 1 Bound to an Allosteric Modulator","volume":"344","author":"Wu","year":"2014","journal-title":"Science"},{"key":"2026090113113049900_cit48","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1021\/op900062p","article-title":"Efficient synthesis\nof 1,4-diaryl-5-methyl-1,2,3-triazole, a potential mGluR1 antagonist,\nand the risk assessment study of arylazides","volume":"13","author":"Tsuritani","year":"2009","journal-title":"Org. Process Res. Dev."},{"key":"2026090113113049900_cit49","unstructured":"Ambler, S. J., Baker, S. R., Clark, B. P., Coleman, D. S., Foglesong, R. J., Goldsworthy, J., Jagdmann, G. E., Jr., Johnson, K. W., Kingston, A. E., Owton, W. M., Schoepp, D. D., Hong, J. E., Schkeryantz, J. M., Vannieuwenhze, M. S., and Zia-Ebrahimi, M. S. (2001) Pharmaceutical Compounds. Patent WO0132632 (A2), USA."},{"key":"2026090113113049900_cit50","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1124\/mol.108.049551","article-title":"Discovery, characterization,\nand\nantiparkinsonian effect of novel positive allosteric modulators of\nmetabotropic glutamate receptor 4","volume":"74","author":"Niswender","year":"2008","journal-title":"Mol. 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