| 词条 | BIIB-104 |
| 释义 |
| Verifiedfields = | Watchedfields = | verifiedrevid = | IUPAC_name = N-[(3S,4S)-4-[4-(5-cyanothiophen-2-yl)phenoxy]oxolan-3-yl]propane-2-sulfonamide | image = PF-04958242_structure.png | width = 250px | tradename = | pregnancy_AU = | pregnancy_US = | pregnancy_category = | legal_AU = | legal_CA = | legal_UK = | legal_US = | legal_status = | routes_of_administration = | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion = | CAS_number_Ref = | CAS_number = 1258963-59-5 | CAS_supplemental = | class = | ATC_prefix = | ATC_suffix = | ATC_supplemental = | PubChem = 49853967 | IUPHAR_ligand = | DrugBank_Ref = | DrugBank = | ChemSpiderID_Ref = | ChemSpiderID = 32698813 | UNII = 9G1A824CC2 | KEGG = | ChEBI = | ChEMBL = | synonyms = PF-04958242 | C=18 | H=20 | N=2 | O=4 | S=2 | molecular_weight = 392.488 g/mol | SMILES = CC(C)S(=O)(=O)N[C@H]1COC[C@H]1OC2=CC=C(C=C2)C3=CC=C(S3)C#N | StdInChI_Ref = | StdInChI = 1S/C18H20N2O4S2/c1-12(2)26(21,22)20-16-10-23-11-17(16)24-14-5-3-13(4-6-14)18-8-7-15(9-19)25-18/h3-8,12,16-17,20H,10-11H2,1-2H3/t16-,17+/m0/s1 | StdInChIKey_Ref = | StdInChIKey = TTYKUKSFWHEBLI-DLBZAZTESA-N }}BIIB-104, also known as PF-04958242 is a positive allosteric modulator (PAM) of the AMPA receptor (AMPAR), an ionotropic glutamate receptor, which is under development by Pfizer for the treatment of cognitive symptoms in schizophrenia.[1][2][3] It was also under development for the treatment of age-related sensorineural hearing loss, but development for this indication was terminated due to insufficient effectiveness.[3][4] As of July 2018, BIIB-104 is in phase II clinical trials for cognitive symptoms in schizophrenia.[3] BIIB-104 belongs to the biarylpropylsulfonamide group of AMPAR PAMs, which also includes LY-404187, LY-503430, and mibampator (LY-451395) among others.[5] It is described as a "high-impact" AMPAR PAM, unlike so-called "low-impact" AMPAR PAMs like CX-516 and its cogener farampator (CX-691, ORG-24448).[2] In animals, low doses of BIIB-104 have been found to enhance cognition and memory, whereas higher doses produce motor coordination disruptions and convulsions.[2] The same effects, as well as neurotoxicity at higher doses, have been observed with orthosteric and other high-impact allosteric AMPAR activators.[2] In healthy volunteers, BIIB-104 has been found to significantly reduce ketamine-induced deficits in verbal learning and working memory without attenuating ketamine-induced psychotomimetic effects.[2] It was able to complete reverse ketamine-induced impairments in spatial working memory in the participants.[2] In addition to its actions on the AMPAR, BIIB-104 has been reported to act as a GlyT1 glycine transporter blocker.[6][7] As such, it is also a glycine reuptake inhibitor, and may act indirectly to activate the glycine receptor and the glycine co-agonist site of the NMDA receptor by increasing extracellular levels of glycine.[6][7] See also
References1. ^{{cite journal | vauthors = 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 CJ | title = 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 = J. Med. Chem. | volume = 58 | issue = 10 | pages = 4291–308 | year = 2015 | pmid = 25905800 | doi = 10.1021/acs.jmedchem.5b00300 }} 2. ^1 2 3 4 5 {{cite journal | vauthors = Ranganathan M, DeMartinis N, Huguenel B, Gaudreault F, Bednar MM, Shaffer CL, Gupta S, Cahill J, Sherif MA, Mancuso J, Zumpano L, D'Souza DC | title = Attenuation of ketamine-induced impairment in verbal learning and memory in healthy volunteers by the AMPA receptor potentiator PF-04958242 | journal = Mol. Psychiatry | volume = | issue = | pages = | year = 2017 | pmid = 28242871 | doi = 10.1038/mp.2017.6 | url = }} 3. ^1 2 {{cite web|url=http://adisinsight.springer.com/drugs/800032498|title=PF 4958242|website=AdisInsight|accessdate=2017-08-30}} 4. ^{{cite journal | vauthors = Bednar MM, DeMartinis N, Banerjee A, Bowditch S, Gaudreault F, Zumpano L, Lin FR | title = The Safety and Efficacy of PF-04958242 in Age-Related Sensorineural Hearing Loss: A Randomized Clinical Trial | journal = JAMA Otolaryngol Head Neck Surg | volume = 141 | issue = 7 | pages = 607–13 | year = 2015 | pmid = 25997115 | doi = 10.1001/jamaoto.2015.0791 | url = }} 5. ^{{cite journal | vauthors = Froestl W, Muhs A, Pfeifer A | title = Cognitive enhancers (nootropics). Part 1: drugs interacting with receptors | journal = J. Alzheimers Dis. | volume = 32 | issue = 4 | pages = 793–887 | year = 2012 | pmid = 22886028 | doi = 10.3233/JAD-2012-121186 | url = }} 6. ^1 {{cite journal | vauthors = Singer P, Dubroqua S, Yee BK | title = Inhibition of glycine transporter 1: The yellow brick road to new schizophrenia therapy? | journal = Curr. Pharm. Des. | volume = 21 | issue = 26 | pages = 3771–87 | year = 2015 | pmid = 26205290 | doi = | url = }} 7. ^1 {{cite journal | vauthors = Mukherjea D, Ghosh S, Bhatta P, Sheth S, Tupal S, Borse V, Brozoski T, Sheehan KE, Rybak LP, Ramkumar V | title = Early investigational drugs for hearing loss | journal = Expert Opin Investig Drugs | volume = 24 | issue = 2 | pages = 201–17 | year = 2015 | pmid = 25243609 | pmc = 5488860 | doi = 10.1517/13543784.2015.960076 | url = }} External links
8 : AMPA receptor positive allosteric modulators|Experimental drugs|Glycine reuptake inhibitors|Nitriles|Nootropics|Sulfonamides|Tetrahydrofurans|Thiophenes |
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