LY-404187

LY-404187
Clinical data
Other names	LY-404,187; N-2-[4-(4-cyanophenyl)phenyl]propyl-2-propanesulfonamide
ATC code	none;
Legal status
Legal status	US: Investigational New Drug;
Identifiers
	IUPAC name N-[2-(4'-cyanobiphenyl-4-yl)propyl]propane-2-sulfonamide;
CAS Number	211311-95-4 ;
ChemSpider	18962921 ;
UNII	75W6I8W6OU;
CompTox Dashboard (EPA)	DTXSID00432983 ;
Chemical and physical data
Formula	C19H22N2O2S
Molar mass	342.46 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES N#Cc2ccc(cc2)-c1ccc(C(C)CNS(=O)(=O)C(C)C)cc1;
	InChI InChI=1S/C19H28N2O2S/c1-14(2)24(22,23)21-13-15(3)17-8-10-19(11-9-17)18-6-4-16(12-20)5-7-18/h4-7,14-15,17,19,21H,8-11,13H2,1-3H3 ; Key:AIALBPYHYGYYRB-UHFFFAOYSA-N ;
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LY-404187 is an AMPA receptor positive allosteric modulator which was developed by Eli Lilly and Company.^[1] It is a member of the biarylpropylsulfonamide class of AMPA receptor potentiators.^[2]

LY-404187 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.^[3] 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.^[4]^[5]

References

^ Jones N, O'Neill MJ, Tricklebank M, Libri V, Williams SC (2005). "Examining the Neural Targets of the AMPA Receptor Potentiator LY404187 in the Rat Brain Using Pharmacological Magnetic Resonance Imaging". Psychopharmacology. 180 (4): 743–751. doi:10.1007/s00213-005-2254-y. PMID 15864556. S2CID 37727259.
^ Ryder JW, Falcone JF, Manro JR, Svensson KA, Merchant KM (2006). "Pharmacological Characterization of cGMP Regulation by the Biarylpropylsulfonamide Class of Positive, Allosteric Modulators of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptors". Journal of Pharmacology and Experimental Therapeutics. 319 (1): 293–298. doi:10.1124/jpet.106.105734. PMID 16803862. S2CID 11732324.
^ Quirk JC, Nisenbaum ES (2002). "LY404187: A Novel Positive Allosteric Modulator of AMPA Receptors". CNS Drug Reviews. 8 (3): 255–282. doi:10.1111/j.1527-3458.2002.tb00228.x. PMC 6741690. PMID 12353058.
^ O'Neill MJ, Bleakman D, Zimmerman DM, Nisenbaum ES (2004). "AMPA Receptor Potentiators for the Treatment of CNS Disorders". Current Drug Targets. CNS and Neurological Disorders. 3 (3): 181–194. doi:10.2174/1568007043337508. PMID 15180479.
^ O'Neill MJ, Witkin JM (2007). "AMPA Receptor Potentiators: Application for Depression and Parkinson's Disease". Current Drug Targets. 8 (5): 603–620. doi:10.2174/138945007780618517. PMID 17504104.

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[pmid15864556-1] Jones N, O'Neill MJ, Tricklebank M, Libri V, Williams SC (2005). "Examining the Neural Targets of the AMPA Receptor Potentiator LY404187 in the Rat Brain Using Pharmacological Magnetic Resonance Imaging". Psychopharmacology. 180 (4): 743–751. doi:10.1007/s00213-005-2254-y. PMID 15864556. S2CID 37727259.

[pmid16803862-2] Ryder JW, Falcone JF, Manro JR, Svensson KA, Merchant KM (2006). "Pharmacological Characterization of cGMP Regulation by the Biarylpropylsulfonamide Class of Positive, Allosteric Modulators of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptors". Journal of Pharmacology and Experimental Therapeutics. 319 (1): 293–298. doi:10.1124/jpet.106.105734. PMID 16803862. S2CID 11732324.

[3] Quirk JC, Nisenbaum ES (2002). "LY404187: A Novel Positive Allosteric Modulator of AMPA Receptors". CNS Drug Reviews. 8 (3): 255–282. doi:10.1111/j.1527-3458.2002.tb00228.x. PMC 6741690. PMID 12353058.

[4] O'Neill MJ, Bleakman D, Zimmerman DM, Nisenbaum ES (2004). "AMPA Receptor Potentiators for the Treatment of CNS Disorders". Current Drug Targets. CNS and Neurological Disorders. 3 (3): 181–194. doi:10.2174/1568007043337508. PMID 15180479.

[5] O'Neill MJ, Witkin JM (2007). "AMPA Receptor Potentiators: Application for Depression and Parkinson's Disease". Current Drug Targets. 8 (5): 603–620. doi:10.2174/138945007780618517. PMID 17504104.

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LY-404187

See also

References