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Review

AMPA Receptor-Positive Allosteric Modulators for the Treatment of Schizophrenia: An Overview of Recent Patent Applications

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Pages 473-491 | Published online: 15 Apr 2015

References

  • Kew JN , KempJA. Ionotropic and metabotropic glutamate receptor structure and pharmacology. Psychopharmacology (Berl.)179 (1), 4–26 (2005).
  • Collingridge GL , OlsenRW, PetersJ, SpeddingM. A nomenclature for ligand-gated ion channels. Neuropharmacology56 (1), 2–5 (2009).
  • Chen PE , WyllieDJ. Pharmacological insights obtained from structure-function studies of ionotropic glutamate receptors. Br. J. Pharmacol.147, 839–853 (2006).
  • Boulter J , HollmannM, O'shea-GreenfieldAet al. Molecular cloning and functional expression of glutamate receptor subunit genes. Science249 (4972), 1033–1037 (1990).
  • Keinanen K , WisdenW, SommerBet al. A family of AMPA-selective glutamate receptors. Science249 (4968), 556–560 (1990).
  • Beneyto M , Meador-WoodruffJH. Expression of transcripts encoding AMPA receptor subunits and associated postsynaptic proteins in the macaque brain. J. Comp. Neurol.468 (4), 530–554 (2004).
  • Shanks NF , MaruoT, FarinaAN, EllismanMH, NakagawaT. Contribution of the global subunit structure and stargazin on the maturation of AMPA receptors. J. Neurosci.30 (7), 2728–2740 (2010).
  • Mayer ML . Structure and mechanism of glutamate receptor ion channel assembly, activation and modulation. Curr. Opin. Neurobiol.21 (2), 283–290 (2011).
  • Sobolevsky AI , RosconiMP, GouauxE. X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor. Nature462 (7274), 745–756 (2009).
  • Mayer ML . Emerging models of glutamate receptor ion channel structure and function. Structure19 (10), 1370–1380 (2011).
  • Ward SE , HarriesM, AldegheriLet al. Integration of lead optimization with crystallography for a membrane-bound ion channel target: discovery of a new class of AMPA receptor positive allosteric modulators. J. Med. Chem.54 (1), 78–94 (2011).
  • Pohlsgaard J , FrydenvangK, MadsenU, KastrupJS. Lessons from more than 80 structures of the GluA2 ligand-binding domain in complex with agonists, antagonists and allosteric modulators. Neuropharmacology60 (1), 135–150 (2011).
  • Weeks AM , HarmsJE, PartinKM, BenvenisteM. Functional insight into development of positive allosteric modulators of AMPA receptors, Neuropharmacology85, 57–66 (2014).
  • Gouaux E . Structure and function of AMPA receptors. J. Physiol.554, 249–253 (2004).
  • Sun Y , OlsonR, HorningM, ArmstrongN, MayerM, GouauxE. Mechanism of glutamate receptor desensitization. Nature417, 245–253 (2002).
  • Tigaret C , ChoquetD. Neuroscience. More AMPAR garnish. Science323 (5919), 1295–1296 (2009).
  • Schwenk J , HarmelN, ZollesGet al. Functional proteomics identify cornichon proteins as auxiliary subunits of AMPA receptors. Science323 (5919), 1313–1319 (2009).
  • Zarate Jr. CA , ManjiHK. The role of AMPA receptor modulation in the treatment of neuropsychiatric diseases. Exp. Neurol.211 (1), 7–10 (2008).
  • Albert JS , WoodMW. Targets and Emerging Therapies for Schizophrenia.Wiley-Blackwell, Oxford (2012).
  • Rankovic Z , BinghamM, NestlerEJ, HargreavesR. Drug Discovery For Psychiatric Disorders.RSC Publishing, Cambridge (2012).
  • Cammarota M , BevilaquaLR, BoniniJS, RossattoJI, MedinaJH, IzquierdoN. Hippocampal glutamate receptors in fear memory consolidation. Neurotox. Res.6 (3), 205–212 (2004).
  • Akhondzadeh S . The glutamate hypothesis of schizophrenia. J. Clin. Pharm. Ther.23 (4), 243–246 (1998).
  • Vignisse J , SteinbuschHW, GrigorievVet al. Concomitant manipulation of murine NMDA- and AMPA-receptors to produce pro-cognitive drug effects in mice, Eur. Neuropsychopharmacol.24 (2), 309–20 (2014).
  • Ward SE , HarriesM. Recent advances in the discovery of selective AMPA receptor positive allosteric modulators. Curr. Med. Chem.17 (30), 3503–3513 (2010).
  • Ward SE , BaxBD, HarriesM. Challenges for and current status of research into positive modulators of AMPA receptors. Br. J. Pharmacol.160 (2), 181–190 (2010).
  • Arai A , KesslerM, Ambros-IngersonJet al. Effects of a centrally active benzoylpyrrolidine drug on AMPA receptor kinetics. Neuroscience75 (2), 573–585 (1996).
  • Lynch G . Memory enhancement: the search for mechanism-based drugs. Nat. Neurosci.5 (Suppl.), 1035–1038 (2002).
  • Woolley ML , WatersKA, GartlonJEet al. Evaluation of the pro-cognitive effects of the AMPA receptor positive modulator, 5-(1-piperidinylcarbonyl)-2,1,3-benzoxadiazole (CX691), in the rat. Psychopharmacology (Berl.)202 (1–3), 343–354 (2009).
  • Watterson LR , Olive, MF. Are AMPA receptor positive allosteric modulators potential pharmacotherapeutics for addiction?Pharmaceuticals7 (1), 29–45, (2014).
  • Lauterborn JC , PinedaE, ChenLY, RamirezEA, LynchG, GallCM. Ampakines cause sustained increases in BDNF signaling at excitatory synapses without changes in AMPA receptor subunit expression. Neuroscience159 (1), 283–295 (2009).
  • Adler LA , KroonRA, SteinMet al. A Translational approach to evaluate the efficacy and safety of the novel AMPA receptor positive allosteric modulator Org 26576 in adult attention-deficit/hyperactivity disorder. Biol. Psychiatry 72 (11), 971–977 (2012).
  • Slverman JL , OliverCF, KarrasMN, GastrellPT, CrawleyJN. AMPAKINE enhancement of social interaction in the BTBR mouse model of autism.Neuropharmacology64, 268–282 (2013).
  • Fan W , WuX, PanYet al. 1-(1,3-Benzodioxol-5-yl-carbo-nyl) piperidine, a modulator of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor, ameliorates exercise-induced fatigue in mice Biol. Pharm. Bull. 37 (1), 13–17 (2014).
  • Ingvar M , Ambros-IngersonJ, DavisMet al. Enhancement by an ampakine of memory encoding in humans. Exp. Neurol.146 (2), 553–559 (1997).
  • Lynch G , GrangerR, Ambros-IngersonJ, DavisCM, KesslerM, SchehrR. Evidence that a positive modulator of AMPA-type glutamate receptors improves delayed recall in aged humans. Exp. Neurol.145 (1), 89–92 (1997).
  • Goff DC , LeahyL, BermanIet al. A placebo-controlled pilot study of the ampakine CX516 added to clozapine in schizophrenia. J. Clin. Psychopharmacol.21 (5), 484–487 (2001).
  • Chappell AS , GonzalesC, WilliamsJ, WitteMM, MohsRC, SperlingR. AMPA potentiator treatment of cognitive deficits in Alzheimer disease. Neurology68 (13), 1008–1012 (2007).
  • Berry-Kravis E , KrauseSE, BlockSSet al. Effect of CX516, an AMPA-modulating compound, on cognition and behavior in fragile X syndrome: a controlled trial. J. Child Adolesc. Psychopharmacol.16 (5), 525–40 (2006).
  • Tolerability and Primary Efficacy of CX516 in Alzheimer's Disease. https://clinicaltrials.gov/ct2/show/NCT00001662
  • A Follow up Safety Study of Patients Who Participated in Previous Studies of the Drug Org 24448. https://clinicaltrials.gov/ct2/show/NCT00780585
  • Org 24448 to Treat Major Depression. https://clinicaltrials.gov/ct2/show/NCT00113022
  • Org 24448 (Ampakine) for Cognitive Deficits in Schizophrenia. https://clinicaltrials.gov/ct2/show/NCT00425815
  • Wesensten NJ , ReichardtRM, BalkinTJ. Ampakine (CX717) effects on performance and alertness during simulated night shift work. Aviat. Space Environ. Med.78 (10), 937–943 (2007).
  • Swanson GT . Targeting AMPA and kainate receptors in neurological disease: therapies on the horizon?Neuropsychopharmacology34, 249–250 (2009).
  • Oertel BG , FeldenL, TranPVet al. Selective antagonism of opioid-induced ventilatory depression by an ampakine molecule in humans without loss of opioid analgesia. Clin. Pharmacol. Ther.87 (2), 204 –2 11 (2010).
  • Cortex's AMPAKINE CX1739 Improves Respiratory Parameters in Obstructive Sleep Apnea Patients. www.thefreelibrary.com/Cortex%27s+AMPAKINE+CX1739+Improves+Respiratory+Parameters+in… -a0248177812
  • Details of the development status of CX1739. www.cortexpharm.com/
  • Nations KR , DogteromP, BursiRet al. Examination of Org 26576, an AMPA receptor positive allosteric modulator, in patients diagnosed with major depressive disorder: an exploratory, randomized, double-blind, placebo-controlled trial. J. Psychopharmacol.26 (12), 1525–1539 (2012).
  • Adler LA , KroonRA, SteinM, ShahidM, TaraziFI. A translational approach to evaluate the efficacy and safety of the novel AMPA receptor positive allosteric modulator org 26576 in adult attention-deficit/hyperactivity disorder. Biol. Psychiatry72 (11), 971–977 (2012) 49.
  • Chapell AS . AMPA potentiator treatment of cognitive deficits in Alzheimer disease, Neurology68 (13), 1008 (2007)
  • Trzepacz PT , CummingsJ, KonechnikTet al. Mibampator (LY451395) randomized clinical trial for agitation/aggression in Alzheimer's disease. Int. Psychogeriatr.25 (5), 707–719 (2013).
  • Evaluation of Single and Repeat Doses of GSK729327 in Healthy Volunteers, https://clinicaltrials.gov/ct2/show/NCT00448890
  • Multiple Ascending Doses of PF-04958242 in Subjects With Stable Schizophrenia (MAD). https://clinicaltrials.gov/ct2/show/NCT02332798
  • Ward SE , HarriesM, AldegheriLet al. Discovery of N-[(2S)-5-(6-fluoro-3-pyridinyl)-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide, a novel clinical AMPA receptor positive modulator. J. Med. Chem.53 (15), 5801–5812 (2010).
  • O'donnell CJ . PF-4958242: a novel AMPA positive allosteric modulator (PAM) for the treatment of cognitive deficits associated with schizophrenia. 242nd ACS Natl Meet. Abst. MEDI27 (2011).
  • Pirotte B , FrancotteP, GoffinE, De TullioP. AMPA receptor positive allosteric modulators: a patent review. Exp. Op. Ther. Patents23 (5), 615–628 (2013).
  • Bradley DM , ChanWN, ThewlisKM, WardSE. Compounds which potentiate AMPA receptor and uses thereof in medicine: WO 2008053031A1 (2008).
  • Bertheleme N , BradleyDM, CardulloFet al. Compounds which potentiate AMPA receptor and uses thereof in medicine: WO 2008113795A1 (2008).
  • Bradley DM , ChanWN, HarrisonSA, ThewlisKM, WardSE. Compounds which potentiate AMPA receptor and uses thereof in medicine: WO 2008110566A1 (2008).
  • Bradley DM , ThewlisKM, WardSE. Compounds which potentiate AMPA receptor and uses thereof in medicine: WO 2008148832A1 (2008).
  • Bradley DM , ChanWN, WardSE. Compounds which potentiate AMPA receptor and uses thereof in medicine: WO 2008148836A1 (2008).
  • Chan WN , HarrisonS, HughesOR, NeesomJK, ThewlisKM, WardSE. Compounds which potentiate AMPA receptor and uses thereof in medicine: WO 2009053448A1 (2009).
  • Chan WN , ThewlisKM, WardSE. Thiazoles which potentiate ampa receptor and medicinal uses thereof: WO 2009053449A1 (2009).
  • Bertheleme N , ChanWN, ScottJS, WardSE. Compounds which potentiate the AMPA receptor and uses thereof in medicine: WO 2009080637A1 (2009).
  • Thewlis KM , WardSE. Compounds which potentiate the AMPA receptor and uses thereof in medicine: WO 2009092712A1 (2009).
  • Thewlis KM , WardSE. Compounds which potentiate the AMPA receptor and uses thereof in medicine: WO 2009092713A1 (2009).
  • Ward SE , BerthelemeN. Compounds which potentiate AMPA receptor and uses thereof in medicine: WO 2010037760A1 (2010).
  • Bradley DM , CardulloF, MarshallH, MarzoratiP, PozzanA, WardSE. Compounds which potentiate the AMPA receptor and uses thereof in medicine: WO 2010066658A1 (2010).
  • Mochizuki M , MiuraS. Heterocyclic compound: WO 2009119088A1 (2009).
  • Mochizuki M , ImaedaT. Heterocyclic compound: WO 2010140339A1 (2010).
  • Mochizuki M , ImaedaT, AsoK. Heterocyclic compound: WO 2011036885A1 (2011).
  • Aso K , MochizukiM, MiuraS, ImaedaT, ToyofukuM. Heterocyclic compound: WO 2011036889A1 (2011).
  • Kori M , ImaedaT, NakamuraSet al. Heterocyclic compound and use thereof: WO 2012020848A1 (2012).
  • Fukumoto S , UjikawaO, MorimotoSet al. Sulfonamide derivative and use thereof: WO 2012137982A2 (2012).
  • Shaffer C L , HurstR S, ScialisR Jet al. Positive allosteric modulation of AMPA receptors from efficacy to toxicity: the interspecies exposure-response continuum of the novel potentiator PF-4778574. J. Pharmacol. Exp. Ther. 347, 212–224 (2013).
  • Patel N C , SchwarzJ, HouX Jet al. Discovery and characterization of a novel dihydroisoxazole class of α‐amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor potentiators. J. Med. Chem. 56, 9180–9191 (2013).
  • Jamieson C , BastenS, CampbellR Aet al. A novel series of positive modulators of the AMPA receptor: discovery and structure based hit-to-lead studies Bioorg. Med. Chem. Lett. (20), 5753–5756 (2010).
  • Jamieson C , BastenS, CampbellR Aet al. A novel series of positive modulators of the AMPA receptor: structure-based lead optimization Bioorg. Med. Chem. Lett. (20) 6072–6075 (2010).
  • Timm D E , BenvenisteM, WeeksAMet al. Structural and functional analysis of two new positive allosteric modulators of GluA2 desensitization and deactivation. Mol. Pharmacol.80, 267–280 (2011).
  • Mueller R , ZhongS, HampsonAet al. Benzoxazinones as potent positive allosteric AMPA receptor modulators: Part I Bioorg. Med. Chem. Lett. (21), 3923–3926 (2011).
  • Mueller R , ZhongS, HampsonAet al. Benzoxazinones as potent positive allosteric AMPA receptor modulators: Part 2 Bioorg. Med. Chem. Lett. (21), 3927–3930 (2011).
  • Mueller R , RachwalS, LeeSet al. Benzotriazinone and benzopyrimidinone derivatives as potent positive allosteric AMPA receptor modulators Bioorg. Med. Chem. Lett. (21), 6170–6175 (2011).
  • Mueller R , RachwalS, VarneyM Aet al. Benzobistriazinones and related heterocyclic ring systems as potent, orally bioavailable positive allosteric AMPA receptor modulators Bioorg. Med. Chem. Lett. (21), 7455–7459 (2011).
  • Bernard K , DanoberL, ThomasJYet al. DRUG FOCUS: S 18986: a positive allosteric modulator of AMPA-type glutamate receptors pharmacological profile of a novel cognitive enhancer. CNS Neurosci. Ther. 16 (5): e193–21 (2010).
  • Norholm A-B , FrancotteP, OlsenLet al. Synthesis, pharmacological and structural characterization, and thermodynamic aspects of GluA2-positive allosteric modulators with a 3,4-dihydro‐2H‐1,2,4-benzothiadiazine 1,1-dioxide scaffold. J. Med. Chem. 56, 8736–8745 (2013).
  • Dintilhac G , ArslanD, DillySet al. New substituted aryl esters and aryl amides of 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides as positive allosteric modulators of AMPA receptors. Med. Chem. Commun. , 2, 509–523 (2011).
  • Battisti U M , OzwiakK, CannazzaGet al. 5-Arylbenzothiadiazine type compounds as positive allosteric modulators of AMPA/kainate receptors. ACS Med. Chem. Lett. 3 (1), 25–29 (2012).
  • Cannazza G , JozwiakK, ParentiCet al. A novel class of allosteric modulators of AMPA/Kainate receptors. Bioorg. Med, Chem. Lett.19, 1254–1257 (2009).
  • Chen H , WangC Z, DingCet al. A combined bioinformatics and chemoinformatics approach for developing asymmetric bivalent AMPA receptor positive allosteric modulators as neuroprotective agents. Chem. Med. Chem. 8, 226–230 (2013).
  • Estep KG , FliriAFJJG, O'donnellC, PatelNC, SchwarzJB, XieL. Oxopiperidinyl and pyranyl sulfonamides as AMPA potentiators: WO 2010038167A1 (2010).
  • Estep KG , O'donnellCJ, XieL. Tetrahydrofuranyl sulfonamides for use as AMPA modulators in the treatment of CNS disorders: WO 2010041162A1 (2010).
  • Fliri AFJJ , GallaschunRJ, O'donnellCJ, SchwarzJB, SegelsteinBE. Heterocyclic sulfonamides, uses and pharmaceutical compositions thereof: WO 2010150192A1 (2010).
  • Estep KG , FliriAFJ, O'donnellCJ. Sulfonamides and pharmaceutical compositions thereof: WO 2008120093A1 (2008).
  • Gillen KJ , JamiesonC, MacleanJKF, MoirEM, RankovicZ. Pyrazolealkanamide substituted thiophenes as ampa potentiators: WO 2008003452A1 (2008).
  • Gillespie J , JamiesonC, MacleanJKF, MoirEM, RankovicZ. Indane derivatives as ampa receptor modulators: WO 2009147167A1 (2009).
  • Gallagher MG , JamiesonC, LyonsAJ, MacleanJKF, MoirEM. Heterocyclic derivatives: WO 2009062930A1 (2009).
  • Gillen KJ , GillespieJ, JamiesonC, MacleanJKF, MoirEM, RankovicZ. Indane derivatives: WO 2010115952A1 (2010).
  • Mueller R , LeeS, O'hareS, RogersG, RachwalS, StreetL. Benzotriazinone derivatives as AMPA receptor enhancers and their preparation, pharmaceutical compositions and use in the treatment of diseases: WO2008085505A1 (2008).
  • Cordi A , RogersG. 3-substituted-[1,2,3]-benzotriazinone compound for enhancing glutamatergic synaptic responses: WO 2008085506A1 (2008).
  • Mueller R , StreetLJ, RachwalS, AlisalaK. Preparation of substituted triazinone derivatives and analogs as glutamatergic synaptic response enhancers: WO2009038752A2 (2009).
  • Cordi A , DesosP, LestageP, DanoberL. Benzothiadiazepine derivatives used as AMPA and NMDA receptor modulators: WO 2010106249A1 (2010).
  • Francotte P , De TullioP, PirotteB, DanoberL, LestageP, CaignardD-H. New cycloalkylated benzothiadiazine derivatives, method for preparing them and pharmaceutical compositions containing them: WO 2010004139A1 (2010).
  • De Tullio P , PirotteB, BotezL, DanoberL, LestageP. Novel derivatives of cyclopropylated benzothiadiazines, method for preparing same and pharmaceutical compositions containing same: WO 2011083265A1 (2011).
  • Francotte P , De TullioP, PirotteB, BotezI, DanoberL, LestageP. Thiochroman derivatives, method for preparing same and pharmaceutical compositions containing same: WO 2011083264A1.
  • Cordi A , DesosP, LestageP, LaurenceD. Dihydrobenzoxathiazepine derivatives, preparation thereof, pharmaceutical compositions and use as ampa receptor modulators: WO 2012035216A1 (2012).
  • Battisti U , CannazzaG, PujaGet al. 1,2,4-Benzothiadiazine dioxide derivatives as allosteric modulators of AMPA receptor and their preparation and use for treatment of mnemocognitive disorders: EP2457906A1 (2012).
  • Zhou, J, ChenHaijun, Johnson, K, WangC. Bivalent AMPA receptor positive allosteric modulators: WO 2013130501A1 (2013).
  • Gouaux JE , SongL, XieY, LandryD. Glur2 Receptor Modulators: WO 2010087982A1 (2010).
  • Zapolsky ME , ZefirovNS, PalyulinVAet al. 4,4′-Biphenylamide derivatives having a pharmacological activity, and medicaments based thereon: WO 2012138254A2 (2012).
  • Zapolsky ME , ZefirovNS, PalyulinVA, LavrovMI. Pharmacologically active alicyclic N,N'-substituted 3,7-diazabicyclo[3. 3. 1]nonane derivatives and drugs based thereon: WO 2012148308A1 (2012).
  • Grove S J A , JamiesonC, MacleanJ F K, MorrowJ A, RankovicZ. Positive allosteric modulators of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor.J. Med. Chem.53 (20) 7271–7279 (2010).
  • Menniti F S , LindsleyC W, ConnP Jet al. Allosteric modulators for the treatment of schizophrenia: targeting glutamatergic networks. Curr. Top. Med. Chem. 13 (1), 26–54 (2014).

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