SETILEUTON

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H17F4N3O4
Molecular Weight	463.3817
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC[C@](O)(C1=NN=C(NCC2=CC=C3C(OC(=O)C=C3C4=CC=C(F)C=C4)=C2)O1)C(F)(F)F

InChI

InChIKey=MAOIDRRXRLYJNV-NRFANRHFSA-N

InChI=1S/C22H17F4N3O4/c1-2-21(31,22(24,25)26)19-28-29-20(33-19)27-11-12-3-8-15-16(10-18(30)32-17(15)9-12)13-4-6-14(23)7-5-13/h3-10,31H,2,11H2,1H3,(H,27,29)/t21-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21325431 | https://www.ncbi.nlm.nih.gov/pubmed/24900191 | https://adisinsight.springer.com/drugs/800024714

Setileuton [MK-0633] is a selective inhibitor of the 5-lipoxygenase enzyme, which was under investigation for the treatment of asthma and atherosclerosis. Setileuton has been in phase II clinical trials by Merck Sharp & Dohme for the treatment of asthma, chronic obstructive pulmonary disease (COPD) and atherosclerosis. However, this research has been discontinued.

Originator

Approval Year

PubMed

Title	Date	PubMed
The discovery of setileuton, a potent and selective 5-lipoxygenase inhibitor.	2010 Jul 8	24900191
Novel cytochrome P450-mediated ring opening of the 1,3,4-oxadiazole in setileuton, a 5-lipoxygenase inhibitor.	2011 May	21325431
The efficacy and tolerability of MK-0633, a 5-lipoxygenase inhibitor, in chronic asthma.	2012 Jan	21945511

Patents

Sample Use Guides

In Vivo Use Guide

This was a randomized, double-blind trial of once-daily Setileuton [MK-0633], 10 mg, 50 mg, and 100 mg, and placebo in patients 18-70 years with a history of chronic asthma, and FEV(1) ≥45 and ≤85% predicted. MK-0633 100 mg was significantly more effective than placebo for the change from baseline in FEV(1) (0.20 L vs. 0.13 L; p = 0.004).

Route of Administration: Oral

In Vitro Use Guide

Setileuton [MK-0633] inhibited 5-LO activity with an IC50 of 3.9 nM in the H5-LO assay and production of LTB4 with IC50 of 52 nM in the HWB assay. This excellent 5-LO inhibitory profile is accompanied by a relatively low affinity for the hERG channel(Ki= 6.3 uM).

Name

Type

Language

SETILEUTON

Official Name

English

SETILEUTON [USAN]

Common Name

English

MK-0633

Code

English

setileuton [INN]

Common Name

English

4-(4-FLUOROPHENYL)-7-(((5-((1S)-1-HYDROXY-1-(TRIFLUOROMETHYL)PROPYL)-1,3,4-OXADIAZOL-2-YL)AMINIUM METHYL-2H-CHROMEN-2-ONE

Common Name

English

2H-1-BENZOPYRAN-2-ONE, 4-(4-FLUOROPHENYL)-7-(((5-((1S)-1-HYDROXY-1-(TRIFLUOROMETHYL)PROPYL)-1,3,4-OXADIAZOL-2-YL)AMINO)METHYL)-

Systematic Name

English

Setileuton [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1322