Chemistry:Ensifentrine
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]
PDE3 inhibitors act as bronchodilators, while PDE4 inhibitors have an anti-inflammatory effect.[2][3]
Ensifentrine was approved for medical use in the United States in June 2024.[1][4][5]
Medical uses
Ensifentrine is indicated for the maintenance treatment of chronic obstructive pulmonary disease in adults.[1]
Pharmacology
It is an analog of trequinsin and, like trequinsin, it is a highly selective inhibitor of the phosphodiesterase enzyme, PDE3; it is >3000-times more potent against PDE3 than PDE4.[2]
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.[6][7][8]: 19–20
In 2005, Rhinopharma Ltd, acquired the rights to the intellectual property from Vernalis.[8]: 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,[8]: 16 and intended to develop ensifentrine, delivered with an inhaler, first for allergic rhinitis, then asthma, then for chronic obstructive pulmonary disease.[8]: 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.[8]
Society and culture
Legal status
Ensifentrine was approved for medical use in the United States in June 2024.[1][4]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Cite error: Invalid
<ref>tag; no text was provided for refs namedOhtuvayre FDA label - ↑ 2.0 2.1 2.2 "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. August 2006. doi:10.1124/jpet.105.099192. PMID 16682455.
- ↑ "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. January 2016. doi:10.1152/ajplung.00324.2015. PMID 26545902.
- ↑ 4.0 4.1 "Novel Drug Approvals for 2024". 1 October 2024. https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2024.
- ↑ (PDF) New Drug Therapy Approvals 2024 (Report). January 2025. https://www.fda.gov/media/184967/download. Retrieved 21 January 2025.
- ↑ Oxford AW, Jack D, "Derivatives of pyrimido[6,1-a]isoquinolin-4-one", EP patent 1165558, published 2002-01-02
- ↑ "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. August 2006. doi:10.1124/jpet.105.099192. PMID 16682455.
- ↑ 8.0 8.1 8.2 8.3 8.4 "Proposed Acquisition of Rhinopharma". Isis Resources plc. 23 August 2006. http://www.veronapharma.com/joomla/images/Documents/verona%20pharma%20admission%20doc.pdf.
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