Chemical compound
Pharmaceutical compound
Ensifentrine Clinical data Trade names Ohtuvayre Other names RPL-554, LS-193,855 AHFS /Drugs.com Monograph MedlinePlus a624040 License data Routes of Inhalation Drug class PDE3 inhibitor /PDE4 inhibitor ATC code Legal status Legal status Identifiers 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 PubChem CID DrugBank ChemSpider UNII KEGG CompTox Dashboard (EPA) Chemical and physical data Formula C 26 H 31 N 5 O 4 Molar mass −1 3D model (JSmol ) 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
Ensifentrine , sold under the brand nameOhtuvayre , is amedication used for the treatment ofchronic obstructive pulmonary disease (COPD) in adults.[ 1] phosphodiesterase 3 inhibitor andphosphodiesterase 4 inhibitor .[ 1] inhalation .[ 1]
PDE3 inhibitors act asbronchodilators , whilePDE4 inhibitors have an anti-inflammatory effect.[ 2] [ 3]
Ensifentrine was approved for medical use in the United States in June 2024.[ 1] [ 4] [ 5]
Ensifentrine isindicated for the maintenance treatment of chronic obstructive pulmonary disease in adults.[ 1]
It is an analog oftrequinsin and, like trequinsin, it is a highly selective inhibitor of thephosphodiesterase enzyme, PDE3; it is >3000-times more potent against PDE3 than PDE4.[ 2]
Ensifentrine was part of a family of compounds invented by Sir David Jack, former head of R&D forGlaxoSmithKline , and Alexander Oxford, a medicinal chemist; the patents on their work were assigned toVernalis plc .[ 6] [ 7] [ 8] : 19–20
In 2005, Rhinopharma Ltd, acquired the rights to the intellectual property from Vernalis.[ 8] : 19–20 [ 8] : 16 inhaler , first forallergic rhinitis , thenasthma , then forchronic obstructive pulmonary disease .[ 8] : 16–17 contract research organization , under the supervision of Oxford, and was studied in collaboration with Page's lab at King’s College, London.[ 2] [ 8]
Society and culture [ edit ] Ensifentrine was approved for medical use in the United States in June 2024.[ 1] [ 4]
^a b c d e f g "Ohtuvayre- ensifentrine suspension" .DailyMed . 18 June 2024. Retrieved15 August 2024 .^a b c Boswell-Smith V, Spina D, Oxford AW, Comer MB, Seeds EA, Page CP (August 2006). "The pharmacology of two novel long-acting phosphodiesterase 3/4 inhibitors, RPL554 [9,10-dimethoxy-2(2,4,6-trimethylphenylimino)-3-(n-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one] and RPL565 [6,7-dihydro-2-(2,6-diisopropylphenoxy)-9,10-dimethoxy-4H-pyrimido[6,1-a]isoquinolin-4-one]".The Journal of Pharmacology and Experimental Therapeutics 318 (2):840– 8.doi :10.1124/jpet.105.099192 .PMID 16682455 .S2CID 15490792 . ^ Turner MJ, Matthes E, Billet A, Ferguson AJ, Thomas DY, Randell SH, et al. (January 2016)."The dual phosphodiesterase 3 and 4 inhibitor RPL554 stimulates CFTR and ciliary beating in primary cultures of bronchial epithelia" .American Journal of Physiology. Lung Cellular and Molecular Physiology 310 (1): L59-70.doi :10.1152/ajplung.00324.2015 PMID 26545902 . ^a b "Novel Drug Approvals for 2024" .U.S.Food and Drug Administration (FDA) . 1 October 2024.Archived from the original on 19 April 2024. Retrieved29 November 2024 .^ New Drug Therapy Approvals 2024 (PDF) .U.S.Food and Drug Administration (FDA) (Report). January 2025.Archived from the original on 21 January 2025. Retrieved21 January 2025 .^ EP 1165558 , Oxford AW, Jack D, "Derivatives of pyrimido[6,1-a]isoquinolin-4-one", published 2 January 2002, assigned to Verona Pharma plc ^ Boswell-Smith V, Spina D, Oxford AW, Comer MB, Seeds EA, Page CP (August 2006). "The pharmacology of two novel long-acting phosphodiesterase 3/4 inhibitors, RPL554 [9,10-dimethoxy-2(2,4,6-trimethylphenylimino)-3-(n-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one] and RPL565 [6,7-dihydro-2-(2,6-diisopropylphenoxy)-9,10-dimethoxy-4H-pyrimido[6,1-a]isoquinolin-4-one]".The Journal of Pharmacology and Experimental Therapeutics 318 (2):840– 848.doi :10.1124/jpet.105.099192 .PMID 16682455 .S2CID 15490792 . ^a b c d e "Proposed Acquisition of Rhinopharma" (PDF) .Isis Resources plc . 23 August 2006. Archived fromthe original (PDF) on 2 March 2016.
