RPL-554
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| Identifiers | |
|---|---|
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| Synonyms | 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 |
| PubChem (CID) | 9934746 |
| ChemSpider |
8110374  |
| Chemical and physical data | |
| Formula | C26H31N5O4 |
| Molar mass | 477.554 g/mol |
| 3D model (Jmol) | Interactive image |
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RPL-554 (LS-193,855) is a drug candidate for respiratory diseases. It is an analog of trequinsin, and like trequinsin, is a dual inhibitor of the phosphodiesterase enzymes PDE-3 and PDE-4.[1] As of October 2015, inhaled RPL-554 delivered via a nebulizer was in development for COPD and had been studied in asthma.[2]
PDE3 inhibitors act as bronchodilators, while PDE4 inhibitors have an anti-inflammatory effect.[1][3]
RPL554 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.[4][5]:19-20
In 2005, Rhinopharma Ltd, acquired the rights to the intellectual property from Vernalis.[5]: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,[5]:16 and intended to develop RPL-554, delivered with an inhaler, first for allergic rhinitis, then asthma, then for COPD.[5]:16-17 RPL554 was synthesized at Tocris, a contract research organization, under the supervision of Oxford, and was studied in collaboration with Page's lab at King’s College, London.[1] In 2006 Rhinopharma recapitalized and was renamed Verona Pharma plc.[5]
References
- 1 2 3 Boswell-Smith V et al. 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]. J Pharmacol Exp Ther. 2006 Aug;318(2):840-8. PMID 16682455
- ↑ Nick Paul Taylor for FierceBiotech. October 1, 2015 Verona sets sights on PhIIb after COPD drug comes through early trial
- ↑ Turner MJ et al. The dual phosphodiesterase 3 and 4 inhibitor RPL554 stimulates CFTR and ciliary beating in primary cultures of bronchial epithelia. Am J Physiol Lung Cell Mol Physiol. 2016 Jan 1;310(1):L59-70. PMID 26545902
- ↑ see US20040171828, identified in the citations of PMID 16682455
- 1 2 3 4 5 ISIS Resources, PLC. August 23, 2006 Proposed Acquisition of Rhinopharma