2015
The Discovery and Characterization of the α‑Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptor Potentiator N‑{(3S,4S)‑4-[4-(5-Cyano-2-thienyl)phenoxy]tetrahydrofuran-3-yl}propane-2-sulfonamide (PF-04958242)
Shaffer CL, Patel NC, Schwarz J, Scialis RJ, Wei Y, Hou XJ, Xie L, Karki K, Bryce DK, Osgood SM, Hoffmann WE, Lazzaro JT, Chang C, McGinnis DF, Lotarski SM, Liu J, Obach RS, Weber ML, Chen L, Zasadny KR, Seymour PA, Schmidt CJ, Hajós M, Hurst RS, Pandit J, O’Donnell C. The Discovery and Characterization of the α‑Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptor Potentiator N‑{(3S,4S)‑4-[4-(5-Cyano-2-thienyl)phenoxy]tetrahydrofuran-3-yl}propane-2-sulfonamide (PF-04958242). Journal Of Medicinal Chemistry 2015, 58: 4291-4308. PMID: 25905800, DOI: 10.1021/acs.jmedchem.5b00300.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdolescentAdultAgedAnimalsBinding SitesDisease Models, AnimalDogsDose-Response Relationship, DrugDrug DiscoveryDrug Evaluation, PreclinicalDrug StabilityFemaleHumansMaleMemory, Short-TermMice, Inbred C57BLMiddle AgedProtein ConformationRats, Sprague-DawleyReceptors, AMPASchizophreniaStructure-Activity RelationshipSulfonamidesThiophenesYoung AdultConceptsΑ-aminoIsoxazolepropionic acid receptor potentiatorsAdequate therapeutic indexPharmacokinetic variabilityClinical studiesReceptor potentiatorsTherapeutic indexPreclinical characterizationCognitive deficitsMetabolic stabilityPhenyl motifLigand-binding domainLead compoundsSubsequent replacementGluA2 ligand-binding domainPatientsSchizophrenia
2013
Discovery and Characterization of a Novel Dihydroisoxazole Class of α‑Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) Receptor Potentiators
Patel NC, Schwarz J, Hou XJ, Hoover DJ, Xie L, Fliri AJ, Gallaschun RJ, Lazzaro JT, Bryce DK, Hoffmann WE, Hanks AN, McGinnis D, Marr ES, Gazard JL, Hajós M, Scialis RJ, Hurst RS, Shaffer CL, Pandit J, O’Donnell C. Discovery and Characterization of a Novel Dihydroisoxazole Class of α‑Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) Receptor Potentiators. Journal Of Medicinal Chemistry 2013, 56: 9180-9191. PMID: 24215237, DOI: 10.1021/jm401274b.Peer-Reviewed Original ResearchConceptsAMPAR potentiatorsStructure-based drug designAcid receptorsΑ-aminoIsoxazolepropionic acid (AMPA) receptorsPositive allosteric modulatorsIsoxazolepropionic acid receptor potentiatorsRat brain homogenatesActivity screenNeuronal precursorsExcitatory neurotransmissionReceptor potentiatorsBrain homogenatesDrug designNeurological disordersAllosteric modulatorsCognitive deficitsX-ray crystal structureNovel ligandsPotentiatorsPotent compoundsADME propertiesDiscoveryCrystal structure
2009
Chronic treatment with AMPA receptor potentiator Org 26576 increases neuronal cell proliferation and survival in adult rodent hippocampus
Su XW, Li XY, Banasr M, Koo JW, Shahid M, Henry B, Duman RS. Chronic treatment with AMPA receptor potentiator Org 26576 increases neuronal cell proliferation and survival in adult rodent hippocampus. Psychopharmacology 2009, 206: 215-222. PMID: 19603152, DOI: 10.1007/s00213-009-1598-0.Peer-Reviewed Original ResearchConceptsOrg 26576Neuronal cell proliferationHippocampal neurogenesisChronic administrationAntidepressant propertiesCell proliferationDentate gyrusPrelimbic cortexMethodsMale Sprague–Dawley ratsAdult rodent hippocampusLast drug injectionDaily intraperitoneal injectionsSprague-Dawley ratsIsoxazolepropionic acid receptor potentiatorsDifferentiation of neuronsRate of survivalResultsAcute administrationAvailable antidepressantsProgenitor cell proliferationChronic treatmentCurrent antidepressantsIntraperitoneal injectionDrug injectionAdult ratsReceptor potentiators
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