Pha-543,613

PHA-543,613
Identifiers
	IUPAC name N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide;
CAS Number	478149-53-0;
PubChem CID	11493927;
IUPHAR/BPS	3998;
ChemSpider	8105752;
UNII	R36R9KVD6Y;
ChEMBL	ChEMBL214268;
Chemical and physical data
Formula	C15H17N3O2
Molar mass	271.314 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1CN2CCC1[C@H](C2)NC(=O)C3=NC=C4C(=C3)C=CO4;
	InChI InChI=1S/C15H17N3O2/c19-15(12-7-11-3-6-20-14(11)8-16-12)17-13-9-18-4-1-10(13)2-5-18/h3,6-8,10,13H,1-2,4-5,9H2,(H,17,19)/t13-/m0/s1; Key:IPKZCLGGYKRDES-ZDUSSCGKSA-N;
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Short description: Chemical compound

PHA-543,613 is a drug that acts as a potent and selective agonist for the α7 subtype of neural nicotinic acetylcholine receptors, with a high level of brain penetration and good oral bioavailability. It is under development as a possible treatment for cognitive deficits in schizophrenia.^[1] It reduces excitotoxicity^[2] and protects striatal dopaminergic neurons in rat models.^[3] It also potentiates cognitive enhancement from memantine,^[4]^[5] decreases dynorphin release^[6] and inhibits GSK-B3.^[7]

References

↑ "Discovery of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide, an agonist of the alpha7 nicotinic acetylcholine receptor, for the potential treatment of cognitive deficits in schizophrenia: synthesis and structure--activity relationship". Journal of Medicinal Chemistry 49 (14): 4425–36. July 2006. doi:10.1021/jm0602413. PMID 16821801.
↑ "Neuroprotective effect of the alpha 7 nicotinic receptor agonist PHA 543613 in an in vivo excitotoxic adult rat model". Neuroscience 356: 52–63. July 2017. doi:10.1016/j.neuroscience.2017.05.019. PMID 28527955. https://zenodo.org/record/1045803.
↑ "Assessment of the Protection of Dopaminergic Neurons by an α7 Nicotinic Receptor Agonist, PHA 543613 Using [(18)FLBT-999 in a Parkinson's Disease Rat Model"]. Frontiers in Medicine 2: 61. 2015. doi:10.3389/fmed.2015.00061. PMID 26389120.
↑ "Potentiation of cognitive enhancer effects of Alzheimer's disease medication memantine by alpha7 nicotinic acetylcholine receptor agonist PHA-543613 in the Morris water maze task". Psychopharmacology 238 (11): 3273–3281. August 2021. doi:10.1007/s00213-021-05942-4. PMID 34387707.
↑ "Cognitive Enhancer Effects of Low Memantine Doses Are Facilitated by an Alpha7 Nicotinic Acetylcholine Receptor Agonist in Scopolamine-Induced Amnesia in Rats". Frontiers in Pharmacology 10: 73. 2019. doi:10.3389/fphar.2019.00073. PMID 30804787.
↑ "Activation of alpha7 acetylcholine receptors reduces neuropathic pain by decreasing dynorphin A release from microglia". Brain Research 1715: 57–65. July 2019. doi:10.1016/j.brainres.2019.03.016. PMID 30898676.
↑ "α7 nicotinic acetylcholine receptor agonism confers neuroprotection through GSK-3β inhibition in a mouse model of intracerebral hemorrhage". Stroke 43 (3): 844–50. March 2012. doi:10.1161/STROKEAHA.111.639989. PMID 22207510.

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[1] "Discovery of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide, an agonist of the alpha7 nicotinic acetylcholine receptor, for the potential treatment of cognitive deficits in schizophrenia: synthesis and structure--activity relationship". Journal of Medicinal Chemistry 49 (14): 4425–36. July 2006. doi:10.1021/jm0602413. PMID 16821801.

[pmid28527955-2] "Neuroprotective effect of the alpha 7 nicotinic receptor agonist PHA 543613 in an in vivo excitotoxic adult rat model". Neuroscience 356: 52–63. July 2017. doi:10.1016/j.neuroscience.2017.05.019. PMID 28527955. https://zenodo.org/record/1045803.

[pmid26389120-3] "Assessment of the Protection of Dopaminergic Neurons by an α7 Nicotinic Receptor Agonist, PHA 543613 Using [(18)FLBT-999 in a Parkinson's Disease Rat Model"]. Frontiers in Medicine 2: 61. 2015. doi:10.3389/fmed.2015.00061. PMID 26389120.

[pmid34387707-4] "Potentiation of cognitive enhancer effects of Alzheimer's disease medication memantine by alpha7 nicotinic acetylcholine receptor agonist PHA-543613 in the Morris water maze task". Psychopharmacology 238 (11): 3273–3281. August 2021. doi:10.1007/s00213-021-05942-4. PMID 34387707.

[pmid30804787-5] "Cognitive Enhancer Effects of Low Memantine Doses Are Facilitated by an Alpha7 Nicotinic Acetylcholine Receptor Agonist in Scopolamine-Induced Amnesia in Rats". Frontiers in Pharmacology 10: 73. 2019. doi:10.3389/fphar.2019.00073. PMID 30804787.

[pmid30898676-6] "Activation of alpha7 acetylcholine receptors reduces neuropathic pain by decreasing dynorphin A release from microglia". Brain Research 1715: 57–65. July 2019. doi:10.1016/j.brainres.2019.03.016. PMID 30898676.

[pmid22207510-7] "α7 nicotinic acetylcholine receptor agonism confers neuroprotection through GSK-3β inhibition in a mouse model of intracerebral hemorrhage". Stroke 43 (3): 844–50. March 2012. doi:10.1161/STROKEAHA.111.639989. PMID 22207510.

v t e Stimulants
Adamantanes	Adapromine Amantadine Bromantane Memantine Rimantadine
Adenosine antagonists	8-Chlorotheophylline 8-Cyclopentyltheophylline 8-Phenyltheophylline Aminophylline Caffeine CGS-15943 Dimethazan Paraxanthine SCH-58261 Theobromine Theophylline
Alkylamines	Cyclopentamine Cypenamine Cyprodenate Heptaminol Isometheptene Levopropylhexedrine Methylhexaneamine Octodrine Propylhexedrine Tuaminoheptane
Ampakines	CX-516 CX-546 CX-614 CX-691 CX-717 IDRA-21 LY-404,187 LY-503,430 Nooglutyl Org 26576 PEPA S-18986 Sunifiram Unifiram
Arylcyclohexylamines	Benocyclidine Dieticyclidine Esketamine Eticyclidine Gacyclidine Ketamine Phencyclamine Phencyclidine Rolicyclidine Tenocyclidine Tiletamine
Benzazepines	6-Br-APB SKF-77434 SKF-81297 SKF-82958
Cholinergics	A-84,543 A-366,833 ABT-202 ABT-418 AR-R17779 Altinicline Anabasine Arecoline Bradanicline Cotinine Cytisine Dianicline Epibatidine Epiboxidine GTS-21 Ispronicline Nicotine PHA-543,613 PNU-120,596 PNU-282,987 Pozanicline Rivanicline Sazetidine A SIB-1553A SSR-180,711 TC-1698 TC-1827 TC-2216 Tebanicline UB-165 Varenicline WAY-317,538
Convulsants	Anatoxin-a Bicuculline DMCM Flurothyl Gabazine Haldol Pentetrazol Picrotoxin Strychnine Thujone
Eugeroics	Adrafinil Armodafinil CRL-40,940 CRL-40,941 Fluorenol Modafinil
Oxazolines	4-Methylaminorex Aminorex Clominorex Cyclazodone Fenozolone Fluminorex Pemoline Thozalinone
Phenethylamines	1-(4-Methylphenyl)-2-aminobutane 1-Methylamino-1-(3,4-methylenedioxyphenyl)propane 2-Fuoroamphetamine 2-Fuoromethamphetamine 2-OH-PEA 2-Phenyl-3-aminobutane 2,3-MDA 3-Fuoroamphetamine 3-Fluoroethamphetamine 3-Fluoromethcathinone 3-Methoxyamphetamine 3-Methylamphetamine 3,4-DMMC 4-BMC 4-CMC 4-Fluoroamphetamine 4-Fluoromethamphetamine 4-MA 4-Methylbuphedrone 4-Methylcathinone 4-MEAP 4-MMA 4-Methylpentedrone 4-MTA 6-FNE AL-1095 Alfetamine a-Ethylphenethylamine Amfecloral Amfepentorex Amfepramone Amidephrine 2-Amino-1,2-dihydronaphthalene 2-Aminoindane 5-(2-Aminopropyl)indole 2-Aminotetralin Acridorex Amphetamine (Dextroamphetamine, Levoamphetamine) Amphetaminil Arbutamine β-Methylphenethylamine β-Phenylmethamphetamine Benfluorex Benzedrone Benzphetamine BDB BOH 3-Benzhydrylmorpholine BPAP Buphedrone Bupropion Butylone Camfetamine Cathine Cathinone Chlorphentermine Cilobamine Cinnamedrine Clenbuterol Clobenzorex Cloforex Clortermine Cypenamine D-Deprenyl Denopamine Dimethoxyamphetamine Dimethylamphetamine Dimethylcathinone Dobutamine DOPA (Dextrodopa, Levodopa) Dopamine Dopexamine Droxidopa EBDB Ephedrine Epinephrine Epinine Etafedrine Ethcathinone Ethylnorepinephrine Ethylone Etilamfetamine Etilefrine Famprofazone Fencamfamin Fencamine Fenethylline Fenfluramine (Dexfenfluramine, Levofenfluramine) Fenproporex Feprosidnine Flephedrone Fludorex Formetorex Furfenorex Gepefrine Hexapradol Hexedrone HMMA Hordenine 4-Hydroxyamphetamine 5-Iodo-2-aminoindane Ibopamine Indanylamphetamine Iofetamine Isoetarine Isoethcathinone Isoprenaline L-Deprenyl (Selegiline) Lefetamine Lisdexamfetamine Lophophine MBDB MDA (tenamfetamine) MDBU MDEA MDMA (midomafetamine) MDMPEA MDOH MDPR MDPEA Mefenorex Mephedrone Mephentermine Metanephrine Metaraminol Mesocarb Methamphetamine (Dextromethamphetamine, Levomethamphetamine) Methoxamine Methoxyphenamine MMA Methcathinone Methedrone Methoxyphenamine Methylenedioxycathinone Methylone Mexedrone MMDA MMDMA MMMA Morforex N,alpha-Diethylphenylethylamine N-Ethylbuphedrone N-Ethylhexedrone N,N-Dimethylphenethylamine Naphthylamphetamine Nisoxetine Norepinephrine Norfenefrine Norfenfluramine Normetanephrine L-Norpseudoephedrine Octopamine (drug) Orciprenaline Ortetamine Oxifentorex Oxilofrine PBA PCA PCMA PHA Pentorex Pentedrone Pentylone Phenatine Phenpromethamine Phentermine Phenylalanine Phenylephrine Phenylpropanolamine Pholedrine PIA PMA PMEA PMMA PPAP Phthalimidopropiophenone Prenylamine Propylamphetamine Pseudoephedrine Ropinirole Salbutamol (Levosalbutamol) Sibutramine Solriamfetol Synephrine Theodrenaline Tiflorex Tranylcypromine Tyramine Tyrosine Xylopropamine Zylofuramine
Phenylmorpholines	3-Fluorophenmetrazine Fenbutrazate Fenmetramide G-130 Manifaxine Morazone Morforex Oxaflozane PD-128,907 Phendimetrazine Phenmetrazine 2-Phenyl-3,6-dimethylmorpholine Pseudophenmetrazine Radafaxine
Piperazines	2C-B-BZP 3C-PEP BZP CM156 DBL-583 GBR-12783 GBR-12935 GBR-13069 GBR-13098 GBR-13119 MeOPP MBZP oMPP Vanoxerine
Piperidines	1-Benzyl-4-(2-(diphenylmethoxy)ethyl)piperidine 2-Benzylpiperidine 2-Methyl-3-phenylpiperidine 3,4-Dichloromethylphenidate 4-Benzylpiperidine 4-Fluoromethylphenidate 4-Methylmethylphenidate Desoxypipradrol Difemetorex Diphenylpyraline Ethylnaphthidate Ethylphenidate Methylnaphthidate Isopropylphenidate JZ-IV-10 Methylphenidate (Dexmethylphenidate) Nocaine Phacetoperane Pipradrol Propylphenidate SCH-5472
Pyrrolidines	2-Diphenylmethylpyrrolidine 5-DBFPV α-PPP α-PBP α-PHP α-PHPP α-PVP α-PVT Diphenylprolinol DMPVP FPOP FPVP MDPPP MDPBP MPBP MPHP MPPP MOPVP MOPPP Indapyrophenidone MDPV Naphyrone PEP Picilorex Prolintane Pyrovalerone
Racetams	Oxiracetam Phenylpiracetam Phenylpiracetam hydrazide
Tropanes	4-fluorotropacocaine 4'-Fluorococaine Altropane (IACFT) Brasofensine CFT (WIN 35,428) β-CIT (RTI-55) Cocaethylene Cocaine Dichloropane (RTI-111) Difluoropine FE-β-CPPIT FP-β-CPPIT Ioflupane (¹²³I) Norcocaine PIT PTT RTI-31 RTI-32 RTI-51 RTI-112 RTI-113 RTI-120 RTI-121 (IPCIT) RTI-126 RTI-150 RTI-177 RTI-229 RTI-336 RTI-354 RTI-371 RTI-386 Salicylmethylecgonine Tesofensine Troparil (β-CPT, WIN 35,065-2) Tropoxane WF-23 WF-33
Tryptamines	4-HO-αMT 4-Methyl-αET 4-Methyl-αMT 5-Chloro-αMT 5-Fluoro-αMT 5-MeO-αET 5-MeO-αMT 5-MeO-DIPT 6-Fluoro-αMT 7-Methyl-αET αET αMT
Others	2-MDP 3,3-Diphenylcyclobutanamine Amfonelic acid Amineptine Amiphenazole Atipamezole Atomoxetine Bemegride Benzydamine BTQ BTS 74,398 Centanafadine Ciclazindol Clofenciclan Cropropamide Crotetamide D-161 Desipramine Diclofensine Dimethocaine Efaroxan Etamivan Fenisorex Fenpentadiol Gamfexine Gilutensin GSK1360707F GYKI-52895 Hexacyclonate Idazoxan Indanorex Indatraline JNJ-7925476 Lazabemide Leptacline Lomevactone LR-5182 Mazindol Meclofenoxate Medifoxamine Mefexamide Methamnetamine Methastyridone Methiopropamine Naphthylaminopropane Nefopam Nikethamide Nomifensine O-2172 Oxaprotiline PNU-99,194 PRC200-SS Rasagiline Rauwolscine Rubidium chloride Setazindol Tametraline Tandamine Thiopropamine Thiothinone Trazium UH-232 Yohimbine
ATC code: N06B

v t e Psychoanaleptics: Anti-dementia agents (ATC code N06D and others)
AChE inhibitor medications	Donepezil Galantamine Ipidacrine Rivastigmine Tacrine
Other medications	Bifemelane Ginkgo folium Meclofenoxate (centrophenoxine) Memantine Nicergoline
Experimental BACE inhibitors	Lanabecestat Verubecestat

Identifiers

IUPAC name N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide
CAS Number	478149-53-0
PubChem CID	11493927
IUPHAR/BPS	3998
ChemSpider	8105752
UNII	R36R9KVD6Y
ChEMBL	ChEMBL214268
Chemical and physical data
Formula	C₁₅H₁₇N₃O₂
Molar mass	271.314 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES C1CN2CCC1[C@H](C2)NC(=O)C3=NC=C4C(=C3)C=CO4
InChI InChI=1S/C15H17N3O2/c19-15(12-7-11-3-6-20-14(11)8-16-12)17-13-9-18-4-1-10(13)2-5-18/h3,6-8,10,13H,1-2,4-5,9H2,(H,17,19)/t13-/m0/s1 Key:IPKZCLGGYKRDES-ZDUSSCGKSA-N
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Pha-543,613

See also

References