{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T16:48:48Z","timestamp":1789145328448,"version":"build-2803163510"},"reference-count":71,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T00:00:00Z","timestamp":1674086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Centre for Research and Development (NCBR)","award":["PBS1\/B7\/8\/2012"],"award-info":[{"award-number":["PBS1\/B7\/8\/2012"]}]},{"name":"Maj Institute of Pharmacology, Polish Academy of Sciences","award":["PBS1\/B7\/8\/2012"],"award-info":[{"award-number":["PBS1\/B7\/8\/2012"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Following the glutamatergic theory of schizophrenia and based on our previous study regarding the antipsychotic-like activity of mGlu7 NAMs, we synthesized a new compound library containing 103 members, which were examined for NAM mGlu7 activity in the T-REx 293 cell line expressing a recombinant human mGlu7 receptor. Out of the twenty-two scaffolds examined, active compounds were found only within the quinazolinone chemotype. 2-(2-Chlorophenyl)-6-(2,3-dimethoxyphenyl)-3-methylquinazolin-4(3H)-one (A9-7, ALX-171, mGlu7 IC50 = 6.14 \u00b5M) was selective over other group III mGlu receptors (mGlu4 and mGlu8), exhibited satisfactory drug-like properties in preliminary DMPK profiling, and was further tested in animal models of antipsychotic-like activity, assessing the positive, negative, and cognitive symptoms. ALX-171 reversed DOI-induced head twitches and MK-801-induced disruptions of social interactions or cognition in the novel object recognition test and spatial delayed alternation test. On the other hand, the efficacy of the compound was not observed in the MK-801-induced hyperactivity test or prepulse inhibition. In summary, the observed antipsychotic activity profile of ALX-171 justifies the further development of the group of quinazolin-4-one derivatives in the search for a new drug candidate for schizophrenia treatment.<\/jats:p>","DOI":"10.3390\/ijms24031981","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T05:06:14Z","timestamp":1674104774000},"page":"1981","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Design and Synthesis of New Quinazolin-4-one Derivatives with Negative mGlu7 Receptor Modulation Activity and Antipsychotic-Like Properties"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9221-947X","authenticated-orcid":false,"given":"Katarzyna","family":"Kaczorowska","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Sm\u0119tna Street, 30-343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Stankiewicz","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Sm\u0119tna Street, 30-343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3741-674X","authenticated-orcid":false,"given":"Ryszard","family":"Bugno","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Sm\u0119tna Street, 30-343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria H.","family":"Paluchowska","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Sm\u0119tna Street, 30-343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2300-0850","authenticated-orcid":false,"given":"Grzegorz","family":"Burnat","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Sm\u0119tna Street, 30-343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Bra\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Sm\u0119tna Street, 30-343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1182-573X","authenticated-orcid":false,"given":"Paulina","family":"Cie\u015blik","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Sm\u0119tna Street, 30-343 Krak\u00f3w, 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Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/0306-4522(95)00244-D","article-title":"Distribution of Metabotropic Glutamate Receptor 7 Messenger RNA in the Developing and Adult Rat Brain","volume":"69","author":"Kinzie","year":"1995","journal-title":"Neuroscience"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1002\/(SICI)1096-9861(19980413)393:3<332::AID-CNE6>3.0.CO;2-2","article-title":"Immunohistochemical Localization of Metabotropic Glutamate Receptors, MGluR7a and MGluR7b, in the Central Nervous System of the Adult Rat and Mouse: A Light and Electron Microscopic Study","volume":"393","author":"Kinoshita","year":"1998","journal-title":"J. Comp. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.1046\/j.1460-9568.2003.02697.x","article-title":"High Level of MGluR7 in the Presynaptic Active Zones of Select Populations of GABAergic Terminals Innervating Interneurons in the Rat Hippocampus","volume":"17","author":"Somogyi","year":"2003","journal-title":"Eur. J. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8734","DOI":"10.1523\/JNEUROSCI.21-22-08734.2001","article-title":"Increased Seizure Susceptibility in Mice Lacking Metabotropic Glutamate Receptor 7","volume":"21","author":"Sansig","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1002\/(SICI)1096-9861(19991213)415:2<266::AID-CNE9>3.0.CO;2-7","article-title":"Localization of Metabotropic Glutamate Receptor 7 MRNA and MGluR7a Protein in the Rat Basal Ganglia","volume":"415","author":"Kosinski","year":"1999","journal-title":"J. Comp. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"316","DOI":"10.3389\/fnmol.2018.00316","article-title":"Negative Allosteric Modulators of mGlu7 Receptor as Putative Antipsychotic Drugs","volume":"11","author":"Kaczorowska","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1046\/j.1460-9568.2003.02667.x","article-title":"Antidepressant and Anxiolytic-like Effects in Mice Lacking the Group III Metabotropic Glutamate Receptor MGluR7","volume":"17","author":"Cryan","year":"2003","journal-title":"Eur. J. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.pharmthera.2018.08.010","article-title":"Depression and Schizophrenia Viewed from the Perspective of Amino Acidergic Neurotransmission: Antipodes of Psychiatric Disorders","volume":"193","author":"Pilc","year":"2019","journal-title":"Pharmacol. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/sj.npp.1300926","article-title":"Metabotropic Glutamate Receptor Subtype 7 Ablation Causes Dysregulation of the HPA Axis and Increases Hippocampal BDNF Protein Levels: Implications for Stress-Related Psychiatric Disorders","volume":"31","author":"Mitsukawa","year":"2006","journal-title":"Neuropsychopharmacology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"10975","DOI":"10.1074\/jbc.M113.542654","article-title":"Blocking Metabotropic Glutamate Receptor Subtype 7 (mGlu7) via the Venus Flytrap Domain (VFTD) Inhibits Amygdala Plasticity, Stress, and Anxiety-Related Behavior","volume":"289","author":"Gee","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.neuropharm.2013.03.028","article-title":"Adult SiRNA-Induced Knockdown of mGlu7 Receptors Reduces Anxiety in the Mouse","volume":"72","author":"Thakker","year":"2013","journal-title":"Neuropharmacology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1124\/jpet.112.200915","article-title":"ADX71743, a Potent and Selective Negative Allosteric Modulator of Metabotropic Glutamate Receptor 7: In Vitro and In Vivo Characterization","volume":"344","author":"Kalinichev","year":"2013","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1038\/sj.mp.4002073","article-title":"MGluR7 Facilitates Extinction of Aversive Memories and Controls Amygdala Plasticity","volume":"13","author":"Fendt","year":"2008","journal-title":"Mol. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"538","DOI":"10.2174\/1389450116666150316224011","article-title":"Metabotropic Glutamate Receptors in Central Nervous System Diseases","volume":"17","author":"Golubeva","year":"2016","journal-title":"Curr. Drug Targets"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1016\/j.neuropharm.2011.10.021","article-title":"Pharmacological Interference with Metabotropic Glutamate Receptor Subtype 7 but Not Subtype 5 Differentially Affects within- and between-Session Extinction of Pavlovian Conditioned Fear","volume":"62","author":"Toth","year":"2012","journal-title":"Neuropharmacology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1021\/acsmedchemlett.7b00317","article-title":"Discovery of VU6005649, a CNS Penetrant MGlu 7\/8 Receptor PAM Derived from a Series of Pyrazolo [1,5-a] Pyrimidines","volume":"8","author":"Abe","year":"2017","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1021\/acs.jmedchem.8b01810","article-title":"Discovery of an Orally Bioavailable and Central Nervous System (CNS) Penetrant MGlu 7 Negative Allosteric Modulator (NAM) in Vivo Tool Compound: N-(2-(1 H-1,2,4-Triazol-1-Yl)-5-(Trifluoromethoxy)Phenyl)-4-(Cyclopropylmethoxy)-3-Methoxybenzamide (VU6012962)","volume":"62","author":"Reed","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"eaai7459","DOI":"10.1126\/scitranslmed.aai7459","article-title":"MGlu7 Potentiation Rescues Cognitive, Social, and Respiratory Phenotypes in a Mouse Model of Rett Syndrome","volume":"9","author":"Gogliotti","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1146\/annurev.pharmtox.011008.145533","article-title":"Metabotropic Glutamate Receptors: Physiology, Pharmacology, and Disease","volume":"50","author":"Niswender","year":"2010","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"387","DOI":"10.3389\/fnmol.2018.00387","article-title":"Metabotropic Glutamate Receptor 7: A New Therapeutic Target in Neurodevelopmental Disorders","volume":"11","author":"Fisher","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1002\/ajmg.b.30865","article-title":"Genome-Wide Association Study of Response to Methylphenidate in 187 Children with Attention-Deficit\/Hyperactivity Disorder","volume":"147","author":"Mick","year":"2008","journal-title":"Am. J. Med. Genet. Part B Neuropsychiatr. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.neuropharm.2007.11.005","article-title":"The Metabotropic Glutamate Receptor 7 (MGluR7) Allosteric Agonist AMN082 Modulates Nucleus Accumbens GABA and Glutamate, but Not Dopamine, in Rats","volume":"54","author":"Li","year":"2008","journal-title":"Neuropharmacology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"738","DOI":"10.2174\/1871527314666150529145332","article-title":"Metabotropic Glutamate Receptor 7 (MGluR7) as a Target for the Treatment of Psychostimulant Dependence","volume":"14","author":"Li","year":"2015","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.neuropharm.2018.01.002","article-title":"Role of mGlu7 Receptor in Morphine Rewarding Effects Is Uncovered by a Novel Orthosteric Agonist","volume":"131","author":"Hajasova","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.pnpbp.2014.11.004","article-title":"AMN082, a Metabotropic Glutamate Receptor 7 Allosteric Agonist, Attenuates Locomotor Sensitization and Cross-Sensitization Induced by Cocaine and Morphine in Mice","volume":"57","author":"Jenda","year":"2015","journal-title":"Prog. Neuro Psychopharmacol. Biol. Psychiatry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1016\/S0028-3908(99)00092-1","article-title":"Pharmacological Agents Acting at Subtypes of Metabotropic Glutamate Receptors","volume":"38","author":"Schoepp","year":"1999","journal-title":"Neuropharmacology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3585","DOI":"10.1021\/jm070262c","article-title":"Synthesis and Biological Evaluation of 1-Amino-2-Phosphonomethylcyclopropanecarboxylic Acids, New Group III Metabotropic Glutamate Receptor Agonists","volume":"50","author":"Sibille","year":"2007","journal-title":"J. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"18712","DOI":"10.1073\/pnas.0508063102","article-title":"A Selective Metabotropic Glutamate Receptor 7 Agonist: Activation of Receptor Signaling via an Allosteric Site Modulates Stress Parameters In Vivo","volume":"102","author":"Mitsukawa","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1124\/jpet.110.177378","article-title":"The Metabotropic Glutamate Receptor 7 Allosteric Modulator AMN082: A Monoaminergic Agent in Disguise?","volume":"338","author":"Leonard","year":"2011","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1111\/j.1369-1600.2010.00310.x","article-title":"Pharmacological Modulation of MGluR7 with AMN082 and MMPIP Exerts Specific Influences on Alcohol Consumption and Preference in Rats","volume":"17","author":"Bahi","year":"2011","journal-title":"Addict. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1016\/j.biopsych.2013.01.021","article-title":"Glutamate-Based Antidepressants: Preclinical Psychopharmacology","volume":"73","author":"Pilc","year":"2013","journal-title":"Biol. Psychiatry"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1097\/j.pain.0000000000000150","article-title":"MMPIP, an MGluR7-Selective Negative Allosteric Modulator, Alleviates Pain and Normalizes Affective and Cognitive Behavior in Neuropathic Mice","volume":"156","author":"Palazzo","year":"2015","journal-title":"Pain"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.neuropharm.2010.07.007","article-title":"Neuropharmacology Allosteric Modulation of Metabotropic Glutamate Receptors: Structural Insights and Therapeutic Potential","volume":"60","author":"Gregory","year":"2011","journal-title":"Neuropharmacology"},{"key":"ref_35","first-page":"21","article-title":"Development of Novel Metabotropic Glutamate Receptor 7 (MGluR7) Negative Allosteric Modulators for Treatment of Anxiety Disorders","volume":"9","author":"Finn","year":"2011","journal-title":"Curr. Neuropharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1021\/acsmedchemlett.7b00429","article-title":"VU6010608, a Novel mGlu7 NAM from a Series of N-(2-(1H-1,2,4-Triazol-1-Yl)-5-(Trifluoromethoxy)Phenyl)Benzamides","volume":"8","author":"Reed","year":"2017","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1016\/j.bmcl.2019.03.016","article-title":"Surveying Heterocycles as Amide Bioisosteres within a Series of MGlu 7 NAMs: Discovery of VU6019278","volume":"29","author":"Reed","year":"2019","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1021\/cn500153z","article-title":"Identi Fi Cation of Positive Allosteric Modulators VU0155094 (ML397) and VU0422288 (ML396) Reveals New Insights into the Biology of Metabotropic Glutamate Receptor 7","volume":"5","author":"Field","year":"2014","journal-title":"ACS Chem. Neurosci."},{"key":"ref_39","first-page":"147","article-title":"In Vitro Pharmacological Characterization of Novel Isoxazolopyridone Derivatives as Allosteric Metabotropic Glutamate Receptor 7 Antagonists","volume":"323","author":"Suzuki","year":"2007","journal-title":"Pharmacology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1021\/acsmedchemlett.0c00432","article-title":"Discovery of VU6027459: A First-in-Class Selective and CNS Penetrant MGlu(7) Positive Allosteric Modulator Tool Compound","volume":"11","author":"Reed","year":"2020","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1177\/1087057114559183","article-title":"Tetracycline-Based System for Controlled Inducible Expression of Group III Metabotropic Glutamate Receptors","volume":"20","author":"Burnat","year":"2015","journal-title":"J. Biomol. Screen."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.tips.2008.10.006","article-title":"Activation of Metabotropic Glutamate Receptors as a Novel Approach for the Treatment of Schizophrenia","volume":"30","author":"Conn","year":"2009","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1107\/S1600576715001132","article-title":"Crystal Structure Determination and Refinement via SIR2014","volume":"48","author":"Burla","year":"2015","journal-title":"J. Appl. Crystallogr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1523\/JNEUROSCI.17-08-02921.1997","article-title":"Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex","volume":"17","author":"Moghaddam","year":"1997","journal-title":"J. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Cie\u015blik, P., and Wiero\u0144ska, J.M. (2020). Regulation of Glutamatergic Activity via Bidirectional Activation of Two Select Receptors as a Novel Approach in Antipsychotic Drug Discovery. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228811"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1176\/ajp.148.10.1301","article-title":"Recent Advances in the Phencyclidine Model of Schizophrenia","volume":"148","author":"Javitt","year":"1991","journal-title":"Am. J. Psychiatry"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1002\/cmdc.202000444","article-title":"Allosteric Molecular Switches in Metabotropic Glutamate Receptors","volume":"16","author":"Ferenczy","year":"2021","journal-title":"ChemMedChem"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.2174\/1570180815666181017131349","article-title":"Challenges in the Discovery and Optimization of MGlu2\/4 Heterodimer Positive Allosteric Modulators","volume":"16","author":"Fulton","year":"2018","journal-title":"Lett. Drug Des. Discov."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4967","DOI":"10.1016\/j.bmcl.2009.07.072","article-title":"Synthesis and SAR of a Novel Positive Allosteric Modulator (PAM) of the Metabotropic Glutamate Receptor 4 (MGluR4)","volume":"19","author":"Williams","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/s00213-011-2502-2","article-title":"Opposing Efficacy of Group III MGlu Receptor Activators, LSP1-2111 and AMN082, in Animal Models of Positive Symptoms of Schizophrenia","volume":"220","author":"Stachowicz","year":"2012","journal-title":"Psychopharmacology"},{"key":"ref_51","unstructured":"Rigaku-Oxford Diffraction (CrysAlisPro, 2006). CrysAlisPro, Release 27-06-2012 CN."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1107\/S0108767307043930","article-title":"A Short History of SHELX","volume":"64","author":"Sheldrick","year":"2008","journal-title":"Acta Crystallogr. Sect. A Found. Crystallogr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1107\/S0021889899006020","article-title":"WinGX Suite for Small-Molecule Single-Crystal Crystallography","volume":"32","author":"Farrugia","year":"1999","journal-title":"J. Appl. Crystallogr."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1107\/S1600576719014092","article-title":"Mercury 4.0: From Visualization to Analysis, Design and Prediction","volume":"53","author":"MacRae","year":"2020","journal-title":"J. Appl. Crystallogr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.neuroscience.2007.07.019","article-title":"Differential Effects of the N-Methyl-d-Aspartate Receptor Antagonist MK-801 on Different Stages of Object Recognition Memory in Mice","volume":"149","author":"Nilsson","year":"2007","journal-title":"Neuroscience"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s00213-014-3657-4","article-title":"The Antipsychotic-like Effects in Rodents of the Positive Allosteric Modulator Lu AF21934 Involve 5-HT1A Receptor Signaling: Mechanistic Studies","volume":"232","author":"Gruca","year":"2015","journal-title":"Psychopharmacology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1016\/j.pnpbp.2008.04.013","article-title":"The Putative Antipsychotic Alstonine Reverses Social Interaction Withdrawal in Mice","volume":"32","author":"Herrmann","year":"2008","journal-title":"Prog. Neuro Psychopharmacol. Biol. Psychiatry"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.neuropharm.2016.06.025","article-title":"Neurochemical and Behavioral Studies on the 5-HT1A-Dependent Antipsychotic Action of the MGlu4 Receptor Agonist LSP4-2022","volume":"115","author":"Acher","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3429","DOI":"10.1021\/jm00097a001","article-title":"Synthesis and Antimalarial Properties of 1-Imino Derivatives of 7-chloro-3-substituted-3,4-dihydro-1,9(2H,10H)-acridinediones and Related Structures","volume":"35","author":"Kesten","year":"1992","journal-title":"J. Med. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4316","DOI":"10.1016\/j.bmcl.2008.06.076","article-title":"4-(1,3-Thiazol-2-yl)morpholine derivatives as inhibitors of phosphoinositide 3-kinase","volume":"18","author":"Alexander","year":"2008","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1021\/jm00137a023","article-title":"Synthesis and Antischistosomal Activity of Certain Pyrazolo[1,5-a]pyrimidines","volume":"408","author":"Senga","year":"1981","journal-title":"J. Med. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"7663","DOI":"10.1021\/jm2010404","article-title":"Synthesis and biochemical evaluation of \u03b4 2-isoxazoline derivatives as DNA methyltransferase 1 inhibitors","volume":"54","author":"Castellano","year":"2011","journal-title":"J. Med. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1021\/ol027283f","article-title":"Facile construction and divergent transformation of polycyclic isoxazoles: Direct access to polyketide architectures","volume":"5","author":"Bode","year":"2003","journal-title":"Org. Lett."},{"key":"ref_64","unstructured":"Gudkov, A. US20200123127A1-Removal of senescence-associated macrophages 2020."},{"key":"ref_65","unstructured":"Shiraishi, M. EP1057812A1-Aminoguanidine hydrazone derivatives, process for producing the same and drugs there of 2000."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Presset, M., Mailhol, D., Coquerel, Y., and Rodriguez, J. (2011). Diazo-transfer reactions to 1,3-dicarbonyl compounds with tosyl azide. Synthesis, 2549\u20132552.","DOI":"10.1055\/s-0030-1260107"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3430","DOI":"10.1002\/ejoc.201402067","article-title":"Regioselective synthesis of highly functionalized furans through the RuII-catalyzed [3+2] cycloaddition of diazodicarbonyl compounds","volume":"2014","author":"Xia","year":"2014","journal-title":"Eur. J. Org. Chem."},{"key":"ref_68","unstructured":"Di Fabio, R. WO2009130231A1-Pyrrolo [1, 2-a] pyrazine derivatives as vasopressin vib receptor antagonists 2009."},{"key":"ref_69","unstructured":"Johan, D., and Oslob, C.H.Y. 20070027166 A1 2007, 1."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"5013","DOI":"10.1021\/jm900851f","article-title":"ATP-competitive inhibitors of the mammalian target of rapamycin: Design and synthesis of highly potent and selective pyrazolopyrimidines","volume":"52","author":"Zask","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.bmcl.2011.10.116","article-title":"3-Mercapto-1,2,4-triazoles and N-acylated thiosemicarbazides as metallo-\u03b2-lactamase inhibitors","volume":"22","author":"Faridoon","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/1981\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:10:19Z","timestamp":1760119819000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/1981"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,19]]},"references-count":71,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24031981"],"URL":"https:\/\/doi.org\/10.3390\/ijms24031981","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,19]]}}}