LY-404,187

drugbox
IUPAC_name = N-2- [4-(4-cyanophenyl)phenyl] propyl 2-propanesulfonamide



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CAS_number = 211311-95-4
synonyms = LY-404,187
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C = 19 | H = 22 | N = 2 | O = 2 | S = 1
molecular_weight = 342.45 g/mol
smiles = N#Cc2ccc(cc2)-c1ccc(C(C)CNS(=O)(=O)C(C)C)cc1
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legal_status = Investigational New Medicine
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LY-404,187 (or LY404187) is an ampakine (or "AMPA receptor potentiator") developed by Eli Lilly and Company.cite journal |author=Jones N, O'Neill MJ, Tricklebank M, Libri V, Williams SC |title=Examining the neural targets of the AMPA receptor potentiator LY404187 in the rat brain using pharmacological magnetic resonance imaging |journal=Psychopharmacology (Berl.) |volume=180 |issue=4 |pages=743–51 |year=2005 |month=August |pmid=15864556 |doi=10.1007/s00213-005-2254-y |url=http://dx.doi.org/10.1007/s00213-005-2254-y] It is a member of the biarylpropylsulfonamide class of ampakines.cite journal |author=Ryder JW, Falcone JF, Manro JR, Svensson KA, Merchant KM |title=Pharmacological characterization of cGMP regulation by the biarylpropylsulfonamide class of positive, allosteric modulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors |journal=J. Pharmacol. Exp. Ther. |volume=319 |issue=1 |pages=293–8 |year=2006 |month=October |pmid=16803862 |doi=10.1124/jpet.106.105734 |url=http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=16803862]

LY-404,187 has been demonstrated to enhance cognitive function in animal studies, and has also shown effects suggesting antidepressant action as well as having possible application in the treatment of schizophrenia, Parkinson's disease and ADHD. These effects appear to be mediated through multiple mechanisms of action secondary to AMPA receptor potentiation, with a prominent effect seen in research being increased levels of BDNF in the brain. [Quirk JC, Nisenbaum ES. LY404187: a novel positive allosteric modulator of AMPA receptors. "CNS Drug Reviews". 2002 Fall;8(3):255-82. PMID 12353058] It may therefore be continued on to human trials, although Eli Lilly has developed a whole family of biarylpropylsulfonamide derivatives and it is unclear at this stage which compound is most likely to be selected for further development. [O'Neill MJ, Bleakman D, Zimmerman DM, Nisenbaum ES. AMPA receptor potentiators for the treatment of CNS disorders. "Current Drug Targets. CNS and Neurological Disorders". 2004 Jun;3(3):181-94. PMID 15180479] [O'Neill MJ, Witkin JM. AMPA receptor potentiators: application for depression and Parkinson's disease. "Current Drug Targets". 2007 May;8(5):603-20. PMID 17504104]

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