VILANTEROL TRIFENATATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C24H33Cl2NO5.C20H16O2
Molecular Weight	774.768
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)C(C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3.OCC4=C(O)C=CC(=C4)[C@@H](O)CNCCCCCCOCCOCC5=C(Cl)C=CC=C5Cl

InChI

InChIKey=KLOLZALDXGTNQE-JIDHJSLPSA-N

InChI=1S/C24H33Cl2NO5.C20H16O2/c25-21-6-5-7-22(26)20(21)17-32-13-12-31-11-4-2-1-3-10-27-15-24(30)18-8-9-23(29)19(14-18)16-28;21-19(22)20(16-10-4-1-5-11-16,17-12-6-2-7-13-17)18-14-8-3-9-15-18/h5-9,14,24,27-30H,1-4,10-13,15-17H2;1-15H,(H,21,22)/t24-;/m0./s1

HIDE SMILES / InChI

Molecular Formula	C24H33Cl2NO5
Molecular Weight	486.429
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	C20H16O2
Molecular Weight	288.3398
Charge	0
Count

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

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203975s003lbl.pdf
Curator's Comment: description was created based on several sources, including http://www.drugbank.ca/drugs/DB09082

Vilanterol (INN, USAN) is an ultra-long-acting β2 adrenoreceptor agonist (ultra-LABA), which was approved in May 2013 in combination with fluticasone furoate for sale as Breo Ellipta by GlaxoSmithKline for the treatment of chronic obstructive pulmonary disease (COPD). Its pharmacological effect is attributable to stimulation of intracellular adenylyl cyclase which catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3’,5’-adenosine monophosphate (cAMP). Increases in cyclic AMP are associated with relaxation of bronchial smooth muscle and inhibition of release of hypersensitivity mediators from mast cells in the lungs. Vilanterol is available in following combinations: a) with inhaled corticosteroid fluticasone furoate — fluticasone furoate/vilanterol (trade names Breo Ellipta , Relvar Ellipta; b) with muscarinic antagonist umeclidinium bromide — umeclidinium bromide/vilanterol (trade name Anoro Ellipta).

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
adrenoceptor beta 2, surface 2 Target ID: P07550 Gene Symbol: ADRB2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203975s000lbl.pdf	Agonist 2678		9.42 null [pKi]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic obstructive pulmonary disease 174 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203975s003lbl.pdf	Secondary		Approved 8429	ANORO ELLIPTA Approved Use ANORO ELLIPTA is a combination of umeclidinium, an anticholinergic, and vilanterol, a long-acting beta2-adrenergic agonist (LABA), indicated for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD). Not indicated for relief of acute bronchospasm or for the treatment of asthma. Launch Date 2013

C_max

Value	Dose	Co-administered	Analyte	Population
205 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25816315/	25 μg 1 times / day multiple, oral dose: 25 μg route of administration: Oral experiment type: MULTIPLE co-administered: UMECLIDINIUM	UMECLIDINIUM	[NO STEREO] VILANTEROL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
239 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25816315/	25 μg 1 times / day multiple, oral dose: 25 μg route of administration: Oral experiment type: MULTIPLE co-administered:		[NO STEREO] VILANTEROL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
495.9 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23284643/	50 μg single, oral dose: 50 μg route of administration: Oral experiment type: SINGLE co-administered:		[NO STEREO] VILANTEROL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
118 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25816315/	25 μg 1 times / day multiple, oral dose: 25 μg route of administration: Oral experiment type: MULTIPLE co-administered: UMECLIDINIUM	UMECLIDINIUM	[NO STEREO] VILANTEROL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
214 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25816315/	25 μg 1 times / day multiple, oral dose: 25 μg route of administration: Oral experiment type: MULTIPLE co-administered:		[NO STEREO] VILANTEROL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
251.4 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23284643/	50 μg single, oral dose: 50 μg route of administration: Oral experiment type: SINGLE co-administered:		[NO STEREO] VILANTEROL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.84 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25816315/	25 μg 1 times / day multiple, oral dose: 25 μg route of administration: Oral experiment type: MULTIPLE co-administered: UMECLIDINIUM	UMECLIDINIUM	[NO STEREO] VILANTEROL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.42 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23284643/	50 μg single, oral dose: 50 μg route of administration: Oral experiment type: SINGLE co-administered:		[NO STEREO] VILANTEROL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
100 ug 1 times / day multiple, respiratory Highest studied dose Dose: 100 ug, 1 times / day Route: respiratory Route: multiple Dose: 100 ug, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23232038	healthy, 29.1 years (range: 21-53 years) n = 9 Health Status: healthy Age Group: 29.1 years (range: 21-53 years) Sex: M Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/23232038	Other AEs: Nasopharyngitis, Constipation... Other AEs: Nasopharyngitis (1 patient) Constipation (1 patient) Hot flush (1 patient) Muscle twitching (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/23232038
500 ug multiple, oral Highest studied dose Dose: 500 ug Route: oral Route: multiple Dose: 500 ug Sources: https://pubmed.ncbi.nlm.nih.gov/23043183	healthy, 33.1 years (range: 19–47 years) n = 9 Health Status: healthy Age Group: 33.1 years (range: 19–47 years) Sex: M Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/23043183	Sources: https://pubmed.ncbi.nlm.nih.gov/23043183
100 ug multiple, respiratory Highest studied dose Dose: 100 ug Route: respiratory Route: multiple Dose: 100 ug Sources: https://pubmed.ncbi.nlm.nih.gov/23232038	unhealthy, 36.9 years (range: 21-60 years) n = 22 Health Status: unhealthy Condition: asthma Age Group: 36.9 years (range: 21-60 years) Sex: M Population Size: 22 Sources: https://pubmed.ncbi.nlm.nih.gov/23232038	Other AEs: Application site rash... Other AEs: Application site rash (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/23232038

AEs

AE	Significance	Dose	Population
Constipation	1 patient	100 ug 1 times / day multiple, respiratory Highest studied dose Dose: 100 ug, 1 times / day Route: respiratory Route: multiple Dose: 100 ug, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23232038	healthy, 29.1 years (range: 21-53 years) n = 9 Health Status: healthy Age Group: 29.1 years (range: 21-53 years) Sex: M Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/23232038
Hot flush	1 patient	100 ug 1 times / day multiple, respiratory Highest studied dose Dose: 100 ug, 1 times / day Route: respiratory Route: multiple Dose: 100 ug, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23232038	healthy, 29.1 years (range: 21-53 years) n = 9 Health Status: healthy Age Group: 29.1 years (range: 21-53 years) Sex: M Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/23232038
Muscle twitching	1 patient	100 ug 1 times / day multiple, respiratory Highest studied dose Dose: 100 ug, 1 times / day Route: respiratory Route: multiple Dose: 100 ug, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23232038	healthy, 29.1 years (range: 21-53 years) n = 9 Health Status: healthy Age Group: 29.1 years (range: 21-53 years) Sex: M Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/23232038
Nasopharyngitis	1 patient	100 ug 1 times / day multiple, respiratory Highest studied dose Dose: 100 ug, 1 times / day Route: respiratory Route: multiple Dose: 100 ug, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23232038	healthy, 29.1 years (range: 21-53 years) n = 9 Health Status: healthy Age Group: 29.1 years (range: 21-53 years) Sex: M Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/23232038
Application site rash	1 patient	100 ug multiple, respiratory Highest studied dose Dose: 100 ug Route: respiratory Route: multiple Dose: 100 ug Sources: https://pubmed.ncbi.nlm.nih.gov/23232038	unhealthy, 36.9 years (range: 21-60 years) n = 22 Health Status: unhealthy Condition: asthma Age Group: 36.9 years (range: 21-60 years) Sex: M Population Size: 22 Sources: https://pubmed.ncbi.nlm.nih.gov/23232038

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	substrate 1037 inhibitor 1767	inhibitor 1852 substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C19 1478 P-gp 1461	P-gp 1537 CYP2C8 693 CYP2C19 991 CYP1A2 1054

Drug as perpetrator

Target	Modality	Activity
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203975Orig1s000ClinPharmR.pdf#page=108 Page: 108.0	no [Inhibition 100 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203975Orig1s000ClinPharmR.pdf#page=107 Page: 107.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203975Orig1s000ClinPharmR.pdf#page=107 Page: 107.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203975Orig1s000ClinPharmR.pdf#page=107 Page: 107.0	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203975Orig1s000ClinPharmR.pdf#page=40 Page: 40.0	yes [IC50 4 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203975Orig1s000ClinPharmR.pdf#page=40 Page: 40.0	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203975Orig1s000ClinPharmR.pdf#page=106 Page: 106.0	minor
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203975Orig1s000ClinPharmR.pdf#page=106 Page: 106.0	minor
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203975Orig1s000ClinPharmR.pdf#page=106 Page: 106.0	minor
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203975Orig1s000ClinPharmR.pdf#page=106 Page: 106.0	minor
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203975Orig1s000ClinPharmR.pdf#page=106 Page: 106.0	minor
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203975Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	yes	unlikely Comment: VI pharmacokinetics was not affected by P-gp inhibition. Drug interaction trials with a specific P-gp inhibitor and fluticasone furoate have not been conducted. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203975Orig1s000ClinPharmR.pdf#page=9 Page: 9.0
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203975Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	yes	yes (co-administration study) Comment: Co-administration with strong CYP3A4 and potent P-gp inhibitor ketoconazole, resulted in modest increases in mean FF AUC(0-24) and Cmax (by 36% and 33%, respectively) and mean VI AUC(0-t) and Cmax (by 65% and 22%, respectively) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203975Orig1s000ClinPharmR.pdf#page=9 Page: 9.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:75037	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:75037
ChemicalBook	CB22542797	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB22542797
MolPort	MolPort-044-560-195	https://www.molport.com/shop/molecule-link/MolPort-044-560-195
ZINC	ZINC000003991624	http://zinc15.docking.org/substances/ZINC000003991624

PubMed

Title	Date	PubMed
Synthesis and structure-activity relationships of long-acting beta2 adrenergic receptor agonists incorporating metabolic inactivation: an antedrug approach.	2010 Jun 10	20462258

Patents

Sample Use Guides

In Vivo Use Guide

ANORO ELLIPTA (umeclidinium/vilanterol 62.5 mcg/25 mcg) should be administered as 1 inhalation once daily by the orally inhaled route only. ANORO ELLIPTA should be used at the same time every day. Do not use ANORO ELLIPTA more than 1 time every 24 hours.

Route of Administration: Respiratory

In Vitro Use Guide

Vilanterol (taken at 1nM) caused concentration related bronchodilation of human small airways when precontracted with histamine or carbachol and exhibited a comparable EC50 and efficacy (maximum percentage bronchodilation) within each spasmogen tested. EC50 value was 0.6 nM.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 19:46:59 GMT 2023` Edited by `admin` on `Fri Dec 15 19:46:59 GMT 2023`
Record UNII	40AHO2C6DG
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

VILANTEROL TRIFENATATE

Official Name

English

VILANTEROL TRIFENATATE [JAN]

Common Name

English

TRIPHENYLACETIC ACID-4-((1R)-2-((6-(2-(2,6-DICHOLOROBENZYL)OXY)ETHOXY)HEXYL)AMINO)-1-HYDROXYETHYL)-2-(HYDROXYMETHYL)PHENOL (1:1)

Common Name

English

VILANTEROL TRIFENATATE COMPONENT ANORO ELLIPTA

Common Name

English

GW642444M

Code

English

VILANTEROL TRIFENATATE [MI]

Common Name

English

ANORO ELLIPTA COMPONENT VILANTEROL TRIFENATATE

Brand Name

English

BREO ELLIPTA COMPONENT VILANTEROL TRIFENATATE

Brand Name

English

VILANTEROL TRIFENATATE [USAN]

Common Name

English

VILANTEROL (AS TRIFENATATE)

Common Name

English

GW-642444M

Code

English

Vilanterol trifenatate [WHO-DD]

Common Name

English

VILANTEROL TRIFENATATE [ORANGE BOOK]

Common Name

English

VILANTEROL TRIFENATATE COMPONENT OF TRELEGY ELLIPTA

Brand Name

English

TRELEGY ELLIPTA COMPONENT VILANTEROL TRIFENATATE

Brand Name

English

TRIPHENYLACETIC ACID-4-((1R)-2-((6-(2-((2,6-DICHLOROBENZYL)OXY)ETHOXY)HEXYL)AMINO)-1-HYDROXYETHYL)-2-(HYDROXYMETHYL)PHENOL (1:1)

Common Name

English

VILANTEROL TRIFENATATE COMPONENT OF BREO ELLIPTA

Brand Name

English

Classification Tree Code System Code

NCI_THESAURUS

C48149