Ensifentrine

Ensifentrine
Clinical data
Trade names	Ohtuvayre
Other names	RPL-554, LS-193,855
AHFS/Drugs.com	Multum Consumer Information
License data	US DailyMed: Ensifentrine;
Routes of; administration	Inhalation
Drug class	PDE3 inhibitor/PDE4 inhibitor
ATC code	None;
Legal status
Legal status	US: ℞-only;
Identifiers
	IUPAC name N-{2-[(2E)-2-(mesitylimino)-9,10-dimethoxy-4-oxo-6,7-dihydro-2H-pyrimido[6,1-a]-isoquinolin-3(4H)-yl]ethyl}urea;
CAS Number	298680-25-8 ; E-isomer: 1884461-72-6;
PubChem CID	9934746;
ChemSpider	8110374 ;
UNII	3E3D8T1GIX;
KEGG	D11743;
CompTox Dashboard (EPA)	DTXSID00183983 ;
ECHA InfoCard	100.245.423
Chemical and physical data
Formula	C26H31N5O4
Molar mass	477.565 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES Cc3cc(C)cc(C)c3N=c2cc1-c(cc4OC)c(cc4OC)CCn1c(=O)n2CCNC(N)=O;
	InChI InChI=1S/C26H31N5O4/c1-15-10-16(2)24(17(3)11-15)29-23-14-20-19-13-22(35-5)21(34-4)12-18(19)6-8-30(20)26(33)31(23)9-7-28-25(27)32/h10-14H,6-9H2,1-5H3,(H3,27,28,32)/b29-23+ ; Key:CSOBIBXVIYAXFM-BYNJWEBRSA-N ;
	(verify)

Ensifentrine, sold under the brand name Ohtuvayre, is a medication used for the treatment of chronic obstructive pulmonary disease (COPD) in adults.^[1] It is a phosphodiesterase 3 inhibitor and phosphodiesterase 4 inhibitor.^[1] It is given by inhalation.^[1]

It is an analog of trequinsin and, like trequinsin, is a highly selective inhibitor of the phosphodiesterase enzyme, PDE3; indeed, it is >3000-times more potent against PDE3 than PDE4.^[2] As of October 2015, inhaled RPL-554 delivered via a nebulizer was in development for COPD and had been studied in asthma.^[3]

PDE3 inhibitors act as bronchodilators, while PDE4 inhibitors have an anti-inflammatory effect.^[2]^[4]

Medical uses

Ensifentrine is indicated for the maintenance treatment of chronic obstructive pulmonary disease in adults.^[1]

History

Ensifentrine was part of a family of compounds invented by Sir David Jack, former head of R&D for GlaxoSmithKline, and Alexander Oxford, a medicinal chemist; the patents on their work were assigned to Vernalis plc.^[5]^[6]^[7]^: 19–20

In 2005, Rhinopharma Ltd, acquired the rights to the intellectual property from Vernalis.^[7]^: 19–20 Rhinopharma was a startup founded in Vancouver, Canada in 2004 by Michael Walker, Clive Page, and David Saint, to discover and develop drugs for chronic respiratory diseases,^[7]^: 16 and intended to develop ensifentrine, delivered with an inhaler, first for allergic rhinitis, then asthma, then for COPD.^[7]^: 16–17 Ensifentrine was synthesized at a contract research organization, under the supervision of Oxford, and was studied in collaboration with Page's lab at King’s College, London.^[2] In 2006 Rhinopharma recapitalized and was renamed Verona Pharma plc.^[7]