LY-404187

Details

Stereochemistry	RACEMIC
Molecular Formula	C19H22N2O2S
Molecular Weight	342.455
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)S(=O)(=O)NCC(C)C1=CC=C(C=C1)C2=CC=C(C=C2)C#N

InChI

InChIKey=HOQAVGZLYRYHSO-UHFFFAOYSA-N

InChI=1S/C19H22N2O2S/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/h4-11,14-15,21H,13H2,1-3H3

HIDE SMILES / InChI

Molecular Formula	C19H22N2O2S
Molecular Weight	342.455
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12353058
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/17504104

LY404187 (or LY-404,187) is a selective, potent and centrally active positive allosteric modulator of AMPA receptors. LY404187 preferentially acts at recombinant human homomeric GluR2 and GluR4 versus GluR1 and GluR3 AMPA receptors. This drug, developed by Eli Lilly and Company, is a member of biarylpropylsulfonamides. LY404187 has been shown to enhance performance in animal models of cognitive function requiring different mnemonic processes and may be therapeutically beneficial for treating cognitive deficits in a variety of disorders, particularly those that are associated with reduced glutamatergic signaling such as schizophrenia. In addition, LY404187 has been demonstrated to be efficacious in animal models of behavioral despair that possess considerable predictive validity for antidepressant activity and Parkinson's disease.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glutamate receptor ionotropic AMPA 41 Target ID: CHEMBL2096670 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12353058	Positive Allosteric Modulator 179

Conditions

Condition	Modality	Targets	Highest Phase	Product
Parkinson's disease 226 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17504104	Primary		Preclinical	Unknown Approved Use Unknown
Depression 235 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17504104	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Novel AMPA receptor potentiators LY392098 and LY404187: effects on recombinant human AMPA receptors in vitro.	2001 Jun	11406188
Neurotrophic actions of the novel AMPA receptor potentiator, LY404187, in rodent models of Parkinson's disease.	2004 Feb 20	14975705

Sample Use Guides

In Vivo Use Guide

in mice: Acute treatment by LY404187: 2.0, 5.0, or 10 mg/kg subcutaneously

Route of Administration: Other

In Vitro Use Guide

LY404187 enhance glutamate (100 uM) stimulated ion influx through recombinant homomeric human AMPA receptor ion channels, GluR1-4, with estimated EC(50) values of 5.65 uM (GluR1(i)), 0.15 uM (GluR2(i)), 1.44 uM (GluR2(o)), 1.66 uM (GluR3(i)) and 0.21 uM (GluR4(i)) for LY404187. Neither compound affected ion influx in untransfected HEK293 cells or GluR transfected cells in the absence of glutamate. This compound was selective for activity at AMPA receptors, with no activity at human recombinant kainate receptors. Electrophysiological recordings demonstrated that glutamate (1 mM)-evoked inward currents in human GluR4 transfected HEK293 cells was potentiated by LY404187 at low concentrations (3-10 nM). In addition, this compound removed glutamate-dependent desensitization of recombinant GluR4 AMPA receptors.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 08:28:10 GMT 2023` Edited by `admin` on `Sat Dec 16 08:28:10 GMT 2023`
Record UNII	75W6I8W6OU
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

LY-404187

Common Name

English

2-PROPANESULFONAMIDE, N-(2-(4'-CYANO(1,1'-BIPHENYL)-4-YL)PROPYL)-

Systematic Name

English

N-2-(4-(4-CYANOPHENYL)PHENYL)PROPYL 2-PROPANESULFONAMIDE

Systematic Name

English

Code System Code Type Description

WIKIPEDIA

LY-404187