LY-334370

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H22FN3O
Molecular Weight	351.4173
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1CCC(CC1)C2=CNC3=C2C=C(NC(=O)C4=CC=C(F)C=C4)C=C3

InChI

InChIKey=MDMJLMDBRQXOOI-UHFFFAOYSA-N

InChI=1S/C21H22FN3O/c1-25-10-8-14(9-11-25)19-13-23-20-7-6-17(12-18(19)20)24-21(26)15-2-4-16(22)5-3-15/h2-7,12-14,23H,8-11H2,1H3,(H,24,26)

HIDE SMILES / InChI

Molecular Formula	C21H22FN3O
Molecular Weight	351.4173
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://adisinsight.springer.com/drugs/800008817
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/15900510 | https://www.ncbi.nlm.nih.gov/pubmed/9641544

LY-334370 is a selective agonist at the serotonin 1F receptor. Lilly had been conducting phase II clinical testing of this compound in Europe as a potential therapy for migraine headaches. Lilly has now announced that it has discontinued commercial development of LY 334370 as a result of a review of data from an ongoing animal toxicology study. It was reported that the compound causes G-protein activation that is mediated by 5-HT1A receptors.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serotonin 1f (5-HT1f) receptor 15 Target ID: CHEMBL1805 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15900510	Agonist 2678		0.446 nM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Migraine 103 Sources: http://adisinsight.springer.com/drugs/800008817	Primary		Phase II 1132	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
200 mg single, oral Highest studied dose Dose: 200 mg Route: oral Route: single Dose: 200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/11675061 Page: p.1233	unhealthy, ADULT n = 26 Health Status: unhealthy Condition: migraine Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 26 Sources: https://pubmed.ncbi.nlm.nih.gov/11675061 Page: p.1233	Other AEs: Asthenia, Dizziness... Other AEs: Asthenia (27%) Dizziness (35%) Somnolence (23%) Paresthesia (19%) Sources: https://pubmed.ncbi.nlm.nih.gov/11675061 Page: p.1233

AEs

AE	Significance	Dose	Population
Paresthesia	19%	200 mg single, oral Highest studied dose Dose: 200 mg Route: oral Route: single Dose: 200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/11675061 Page: p.1233	unhealthy, ADULT n = 26 Health Status: unhealthy Condition: migraine Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 26 Sources: https://pubmed.ncbi.nlm.nih.gov/11675061 Page: p.1233
Somnolence	23%	200 mg single, oral Highest studied dose Dose: 200 mg Route: oral Route: single Dose: 200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/11675061 Page: p.1233	unhealthy, ADULT n = 26 Health Status: unhealthy Condition: migraine Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 26 Sources: https://pubmed.ncbi.nlm.nih.gov/11675061 Page: p.1233
Asthenia	27%	200 mg single, oral Highest studied dose Dose: 200 mg Route: oral Route: single Dose: 200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/11675061 Page: p.1233	unhealthy, ADULT n = 26 Health Status: unhealthy Condition: migraine Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 26 Sources: https://pubmed.ncbi.nlm.nih.gov/11675061 Page: p.1233
Dizziness	35%	200 mg single, oral Highest studied dose Dose: 200 mg Route: oral Route: single Dose: 200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/11675061 Page: p.1233	unhealthy, ADULT n = 26 Health Status: unhealthy Condition: migraine Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 26 Sources: https://pubmed.ncbi.nlm.nih.gov/11675061 Page: p.1233

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00AL83	https://www.1pchem.com/search?query=1P00AL83
AChemBlock	Q70200	http://www.achemblock.com/catalogsearch/result/?q=Q70200
Angene	AGN-PC-02ISQ2	http://www.angenechemical.com/productshow/AGN-PC-02ISQ2.html
ApexBio Technology	B7267	https://www.apexbt.com/catalogsearch/result/?q=B7267
Axon MedChem	1612	https://www.axonmedchem.com/product/1612
BLD Pharm	BD559258	http://www.bldpharm.com/search/Search.html?keyword=BD559258
BOC Sciences	182563-08-2	http://www.bocsci.com/description.asp?cas=182563-08-2
Chem Scene	CS-0025021	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0025021
ChemShuttle	113719	https://www.chemshuttle.com/catalogsearch/result/?q=113719
Lab Network	LN00334306	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00334306
Matrix Scientific	147806	http://www.matrixscientific.com/147806.html
MedChem Express	HY-103107	https://www.medchemexpress.com/search.html?q=HY-103107&ft=&fa=&fp=
MolPort	MolPort-023-276-654	https://www.molport.com/shop/molecule-link/MolPort-023-276-654
MolPort	MolPort-035-936-419	https://www.molport.com/shop/molecule-link/MolPort-035-936-419
Molnova	M18144	https://www.molnova.com/en/serch-list.html?keywords=M18144
MuseChem	I007844	https://www.musechem.com/product/I007844.html
MuseChem	I012956	https://www.musechem.com/product/I012956.html
Princeton BioMolecular Research	PBMR221955	http://www.princetonbio.com/order_online?common_id=PBMR221955
ShangHai Biochempartner	BCP29131	http://www.biochempartner.com/search_BCP29131
TargetMol	T4266	https://www.targetmol.com/search?keyword=T4266
Tocris	3079	https://www.tocris.com/search.php?Type=QuickSearch&Value=3079
eMolecules	24950869	https://orderbb.emolecules.com/search/#?query=24950869
eMolecules	300123789	https://orderbb.emolecules.com/search/#?query=300123789
eMolecules	36367185	https://orderbb.emolecules.com/search/#?query=36367185
mcule	MCULE-5931963296	https://mcule.com/MCULE-5931963296/
mcule	MCULE-6812742236	https://mcule.com/MCULE-6812742236/

PubMed

Title	Date	PubMed
G-protein activation at 5-HT1A receptors by the 5-ht1F ligand LY334370 in guinea-pig brain sections and recombinant cell lines.	1998 May	9641544
Possible antimigraine mechanisms of action of the 5HT1F receptor agonist LY334370.	1999 Dec	10668103
Ligands for the investigation of 5-HT autoreceptor function.	2001 Nov 15	11750791
Selective seratonin 1F (5-HT(1F)) receptor agonist LY334370 for acute migraine: a randomised controlled trial.	2001 Oct 13	11675061
Crystal forms of LY334370 HCl: isolation, solid-state characterization, and physicochemical properties.	2003 Jun	12761809
[3H]LY334370, a novel radioligand for the 5-HT1F receptor. I. In vitro characterization of binding properties.	2005 Mar	15900510
[3H]LY334370, a novel radioligand for the 5-HT1F receptor. II. Autoradiographic localization in rat, guinea pig, monkey and human brain.	2005 Mar	15900511
Designing selective, high affinity ligands of 5-HT1D receptor by covalent dimerization of 5-HT1F ligands derived from 4-fluoro-N-[3-(1-methyl-4-piperidinyl)-1H-indol-5-yl]benzamide.	2008 Jun 26	18507369
Targeting to 5-HT1F receptor subtype for migraine treatment: lessons from the past, implications for the future.	2012 Dec	22934751
Agonism of the 5-hydroxytryptamine 1F receptor promotes mitochondrial biogenesis and recovery from acute kidney injury.	2014 Aug	24849926

Patents

Sample Use Guides

In Vivo Use Guide

LY334370 (20, 60, or 200 mg) was given to outpatients with moderate or severe migraine headaches in a double blind, parallel group study

Route of Administration: Oral

In Vitro Use Guide

1–100 nM LY334370 increased carbonylcyanide-p-trifluoromethoxyphenylhydrazone–uncoupled oxygen consumption in renal proximal tubule cells

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:52:04 UTC 2023` Edited by `admin` on `Fri Dec 15 15:52:04 UTC 2023`
Record UNII	5Q7I1WL2UY
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

LY-334370

Code

English

4-FLUORO-N-(3-(1-METHYLPIPERIDIN-4-YL)-1H-INDOL-5-YL)BENZAMIDE

Systematic Name

English

BENZAMIDE, 4-FLUORO-N-(3-(1-METHYL-4-PIPERIDINYL)-1H-INDOL-5-YL)-

Systematic Name

English

LY334370

Code

English

Code System Code Type Description

CAS

182563-08-2